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Sample records for title compound c11h11nos2

  1. 11 CFR 102.11 - Petty cash fund (2 U.S.C. 432(h)(2)).

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Petty cash fund (2 U.S.C. 432(h)(2)). 102.11 Section 102.11 Federal Elections FEDERAL ELECTION COMMISSION GENERAL REGISTRATION, ORGANIZATION, AND... and Congressional district) sought by such candidate. ...

  2. 7-Chloro-11a-phenyl-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione

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    Vahan Martirosyan

    2008-03-01

    Full Text Available The title compound, C18H15ClN2O2, is a potential human immunodeficiency virus type-1 (HIV-1 non-nucleoside reverse transcriptase inhibitor. The pyrrolidine ring adopts an envelope and the diazepine ring a boat conformation. In the crystal structure, two isomers (R and S form centrosymmetric dimers via N—H...O hydrogen bonds.

  3. 1-/sup 11/C-D-glucose and related compounds

    Energy Technology Data Exchange (ETDEWEB)

    Shiue, C.Y.; Wolf, A.P.

    1982-01-26

    The novel compounds 1-/sup 11/C-D-glucose, 1-/sup 11/C-D-mannose, 1-/sup 11/C-D-galactose, 2-/sup 11/C-D-glucose, 2-/sup 11/C-D-mannose and 2-/sup 11/C-D-galactose which can be used in nuclear medicine to monitor the metabolism of glucose and galactose can be rapidly prepared by reaction of the appropriate aldose substrate with an alkali metal /sup 11/C-labeled cyanide followed by reduction with a Raney alloy in formic acid.

  4. Radiosynthesis of the D2/3 agonist [3-11C]-(+)-PHNO using [11C]iodomethane

    International Nuclear Information System (INIS)

    Francisco Garcia-Arguello, Segundo; Fortt, Robin; Steel, Colin J.; Brickute, Diana; Glaser, Matthias; Turton, David R.; Robins, Edward G.; Årstad, Erik; Luthra, Sajinder K.

    2013-01-01

    We report here a radiosynthesis for the D 2/3 agonist (+)-4-([3- 11 C]propyl)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-ol (3-[ 11 C]-(+)-PHNO) labelled at the terminal carbon of the N-propyl chain. The protocol is based on 11 C-methylation of an N-acetyl precursor. This initial step is followed by a reduction with LiAlH 4 to give ([3- 11 C]-(+)-PHNO). We first applied the method for the synthesis of a model compound, N-3-([ 11 C]propyl)-1,2,3,4-tetrahydroisoquinoline, which we obtained in 77–97% analytical radiochemical yield (n=6) in 20 min. Similarly, we prepared ([3- 11 C]-(+)-PHNO) in 55–60% analytical radiochemical yield (n=5) using a one-pot procedure. We have also been able to implement the complete process on a semi-automated module. This platform delivered purified and formulated [3- 11 C]PHNO with an average radiochemical yield of 9% (n=13, range 2–30%, non-decay corrected), a radiochemical purity >95%, and a specific radioactivity of 26.8–81.1 GBq/μmol in a total time of 63–65 min. - Highlights: ► We report an alternative method to obtain carbon-11 labelled PHNO. ► The method is based on readily available [ 11 C]methyl iodide as starting material. ► We have automated the alkylation/reduction protocol including purification and formulation

  5. Thermal stability of polyoxometalate compound of Keggin K8[2-SiW11O39]∙nH2O supported with SiO2

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    Yunita Sari M A

    2017-06-01

    Full Text Available Synthesis through sol-gel method and characterization of polyoxometalate compound of K8[b2-SiW11O39]∙nH2O supported with SiO2 have been done. The functional groups of polyoxometalate compound  was characterized by FT-IR spectrophotometer for the fungtional groups and the degree’s of crystalinity  using XRD. The acidity of K8[b2-SiW11O39]∙nH2O/SiO2 was determined qualitative analysis using ammonia and pyridine adsorption and the quantitative analysis using potentiometric titration method. The results of FT-IR spectrum of K8[b2-SiW11O39]∙nH2O appeared at  wavenumber 987.55 cm-1 (W=O, 864.11 cm-1 (W-Oe-W, 756.1 cm-1 (W-Oc-W, 3425.58 cm-1 (O-H, respectively and spectrum of  K8[b2-SiW11O39]SiO2 appeared at wavenumber  956.69 cm-1 (W=O, 864.11 cm-1 (W-Oe-W, 3448.72 cm-1 (O-H, respectively. The diffraction of XRD pattern of K8[b2-SiW11O39]∙nH2O and K8[b2-SiW11O39]∙nH2O/SiO2 compounds show high crystalinity. The acidic properties showed K8[b2-SiW11O39]∙nH2O/SiO2 more acidic compared to K8[b2-The SiW11O39]∙nH2O. The qualitative analysis showed pyridine compound adsorbed more of polyoxometalate compound of K8[b2-SiW11O39]∙nH2O/SiO2. Analysis of stability showed that the K8[b2-SiW11O39]∙nH2O/SiO2 at temperature 500°C has structural changes compare to 200-400oC which was indicated from vibration at wavenumber 800-1000 cm-1. Keywords : K8[b2-SiW11O39]∙nH2O, polyoxometalate, SiO2.

  6. 1,5-Dimethyl-2-phenyl-1H-pyrazol-3(2H-one–4,4′-(propane-2,2-diylbis[1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H-one] (1/1

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    Krzysztof Lyczko

    2013-01-01

    Full Text Available The asymmetric unit of the title compound, C11H12N2C25H28N4O2, contains two different molecules. The smaller is known as antipyrine [systematic name: 1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H-one] and the larger is built up from two antypirine molecules which are connected through a C atom of the pyrazolone ring to a central propanyl part [systematic name: 4,4′-(propane-2,2-diylbis[1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H-one]. Intramolecular C—H...O hydrogen bonds occur in the latter molecule. In the crystal, C—H...O hydrogen bonds link the molecules into a two-dimensional network parallel to (001.

  7. Routine production of H11CN and :11C:-1-aminocyclopentanecarboxylic acid

    International Nuclear Information System (INIS)

    Sambre, J.; Vandecasteele, C.; Geothals, P.; Rabi, N.A.; Haver, D. van; Slegers, G.

    1985-01-01

    The production of H 11 CN using the 14 N(p,α) 11 C reaction, was studied. The yield is 140 mCi/μA at saturation (EOB). From 1.8 Ci of H 11 CN 140 mCi of [ 11 C]ACPC are produced routinely and under remote-control. Chemical and pharmaceutical controls showed that the product is suitable for injection. (author)

  8. [11C]copper(I) cyanide: a new radioactive precursor or 11C-cyanation and functionalization of haloarenes

    International Nuclear Information System (INIS)

    Ponchant, M.; Hinnen, F.; Demphel, S.; Crouzel, C.

    1997-01-01

    Radiosyntheses of [cyano- 11 C]benzonitriles, [carboyxyl- 11 C]benzoic acids, [carbonyl- 11 C]benzamides and [tetrazoyl- 11 C]5-biphenyl-1H-tetrazoles are described. [Cyano- 11 C]benzonitriles were prepared using the Rosenmund-von Braun reaction in one step from [ 11 C]hydrogen cyanide via [ 11 C]copper(1) cyanide in 2 min. [Carboxyl- 11 C]benzoic acids and [carbonyl- 11 C]benzamides were prepared from [cyano- 11 C]benzonitrile-complexes using basic hydrogen peroxide for 3 min in N,N-dimethylformamide at 180 and 80 o C, respectively. [Tetrazoyl- 11 C]5-biphenyl-1H-tetrazoles were obtained from [cyano- 11 C]benzonitrile-complexes in 7 min by cyclization with trimethyltin azide followed by acid hydrolysis at 180 o C. These labelled compounds were obtained in a one-pot procedure with good average specific radioactivities [500 mCi/μmol) at the end of synthesis] and in satisfactory average radiochemical yields (24-69%) at 40 min from the end of radionuclide production. This new radioactive precursor, [ 11 C]copper(I) cyanide, should give access to new 11 C-labelled ligands for positron emission tomography. (author)

  9. Preparation of [11C]diethyl oxalate and [11C]oxalic acid and demonstration of their use in the synthesis of [11C]-2,3-dihydroxyquinoxaline

    International Nuclear Information System (INIS)

    Thorell, J.-O.; Stone-Elander, S.

    1993-01-01

    A method for the production of two new carbon-11 labelled difunctional radiolabelling precursors, [ 11 C]diethyl oxalate,2, and [ 11 C]oxalic acid, 3 is described. Methyl chloroformate was reacted with no-carrier-added [ 11 C]cyanide to generate the intermediate nitrile, methyl [ 11 C]cyanoformate. Alcoholysis with HC1 in ethanol generated 2, which could subsequently be converted to 3 with aqueous acid. The total time of preparation from end-or-trapping of [ 11 C]cyanide was 6-7 min using combined microwave and thermal treatment or, by exclusively thermal treatment, 15 and 20 min for 2 and 3, respectively. The radiochemical conversion of [ 11 C]cyanide to 2 and 3 was ∼ 80% and ∼ 70%, respectively. Both 2 and 3 were used in a model reaction with 1,2-phenylenediamine to synthesize the heterocyclic compound, 2,3-dihydroxyquinoxaline, a basic structural unit in antagonists for the excitatory amino acid receptor system. (Author)

  10. Benzene-1,2-dicarboxylic acid–pyridinium-2-olate (1/1

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    Chua-Hua Yu

    2012-07-01

    Full Text Available The asymmetric unit of the title compound, C5H5NO·C8H6O4, contains one o-phthalate acid molecule and one pyridin-2-ol molecule, which exists in a zwitterionic form. In the o-phthalate acid molecule, the carboxylate groups are twisted from the benzene ring by dihedral angles of 13.6 (1° and 73.1 (1°; the hydroxy H atom in the latter group is disordered over two positons in a 1:1 ratio. In the crystal, O—H...O and N—H...O hydrogen bonds link the molecules into zigzag chains in [-101].

  11. (S-1-[3,5-Bis(trifluoromethylphenyl]-N-methylethylamine–(R-2-hydroxybutanedioic acid (1/1

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    Hai-Bin Zhu

    2009-01-01

    Full Text Available In the title compound, C11H11F6N·C4H6O5, a key intermediate in the synthesis of the NK1 receptor antagonist of casopitant, the F atoms of the trifluoromethyl groups are disordered over two sites with equal occupancies. In the crystal, the components are linked by bifurcated N—H...(O,O hydrogen bonds.

  12. Design and Synthesis of 11C-Labelled Compound Libraries for the Molecular Imaging of EGFr, VEGFr-2, AT1 and AT2 Receptors: Transition-Metal Mediated Carbonylations Using [11C]Carbon Monoxide

    International Nuclear Information System (INIS)

    Aaberg, Ola

    2009-01-01

    This work deals with radiochemistry and new approaches to develop novel PET tracers labelled with the radionuclide 11 C. Two methods for the synthesis of 11 C-labelled acrylamides have been explored. First, [1- 11 C]-acrylic acid was obtained from a palladium(0)-mediated 11 C-carboxylation of acetylene with [ 11 C]carbon monoxide; this could be converted to the corresponding acyl chloride and then combined with benzylamine to form N-benzyl[carbonyl- 11 C]acrylamide. In the second method, the palladium(0)-mediated carbonylation of vinyl halides with [ 11 C]carbon monoxide was explored. This latter method, yielded labelled acrylamides in a single step with retention of configuration at the C=C double bond, and required less amine compared to the acetylene method. The vinyl halide method was used to synthesize a library of 11 C-labelled EGFr-inhibitors in 7-61% decay corrected radiochemical yield via a combinatorial approach. The compounds were designed to target either the active or the inactive form of EGFr, following computational docking studies. The rhodium(I)-mediated carbonylative cross-coupling of an azide and an amine was shown to be a very general reaction and was used to synthesize a library of dual VEGFr-2/PDGFrβ inhibitors that were 11 C-labelled at the urea position in 38-78% dc rcy. The angiotensin II AT 1 receptor antagonist eprosartan was 11 C-labelled at one of the carboxyl groups in one step using a palladium(0)-mediated carboxylation. Autoradiography shows specific binding in rat kidney, lung and adrenal cortex, and organ distribution shows a high accumulation in the intestines, kidneys and liver. Specific binding in frozen sections of human adrenal incidentalomas warrants further investigations of this tracer. Three angiotensin II AT 2 ligands were 11 C-labelled at the amide group in a palladium(0)-mediated aminocarbonylation in 16-36% dc rcy. One of the compounds was evaluated using in vitro using autoradiography, and in vivo using organ

  13. 5,11-Ditosyl-5H,11H-dibenzo[b,f][1,5]diazocine-6,12-dione acetic acid hemisolvate

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    Najat Abbassi

    2013-04-01

    Full Text Available The molecular structure of the title compound, C28H22N2O6S2·0.5CH3COOH, is built up from three fused rings, two six and one eight membered. The eight-membered ring shows a boat conformation and the dihedral angle between the two benzene groups attached thereto is 66.43 (11°, resulting in a V-shaped geometry. Two tosyl substituents are bound to the N atoms. The planes through the tolyl rings are roughly perpendicular, as indicated by the dihedral angle of 82.44 (12°. In the crystal, the molecule and its inversion-related symmetry-equivalent are linked to the acetic acid solvent molecule by non-classical O—H...O and C—H...O hydrogen bonds. Two half-occupied acetic acid solvent molecules are disordered at the same site and linked by a center of symmetry.

  14. Molecular and crystal structure of nido-9-C5H5N-11-I-7,8-C2B9H10: supramolecular architecture via hydrogen bonding X-H...I (X = B, C)

    International Nuclear Information System (INIS)

    Polyanskaya, T.M.

    2006-01-01

    A monocrystal X-ray diffraction study of a new iodine-containing cluster compound 9-(pyridine)-11-iodo-decahydro-7,8-dicarba-nido-undecaborane [9-C 5 H 5 N-11-I-7,8-C 2 B 9 H 10 ] has been performed. Crystal data: C 7 H 15 B 9 NI, M = 337.39, monoclinic, space group P2 1 /c, unit cell parameters: a=9.348(1) A, b=11.159(1) A, c=13.442(2) A, β=98.13(1) deg, V=1388.1(5) A 3 , Z=4, d calc = 1.614 g/cm 3 , T = 295 K, F(000)=648, μ=2.276 mm -1 . The structure was solved by a direct method and refined in the full-matrix anisotropic approximation (isotropic for hydrogen atoms) to final agreement factors R 1 = 0.0254, wR 2 = 0.0454 for 2437 I hkl >2σ I from 3590 measured I hkl (an Enraf-Nonius CAD-4 diffractometer, λMoK α , graphite monochromator, θ/2θ-scanning). The molecules are joined into a supramolecular assembly by hydrogen bonds X-H...I (X = B, C) [ru

  15. A novel synthesis of octahydropyrido[3,2-c]carbazole framework of aspidospermidine alkaloids and a combined computational, FT-IR, NMR, NBO, NLO, FMO, MEP study of the cis-4a-Ethyl-1-(2hydroxyethyl)-2,3,4,4a,5,6,7,11c-octahydro-1H-pyrido[3,2-c]carbazole

    Science.gov (United States)

    Uludağ, Nesimi; Serdaroğlu, Goncagul; Yinanc, Abdullah

    2018-06-01

    In this study, we performed a novel synthesis of the octahydropyrido[3,2-c]carbazole derivative 6 from 1 in five steps with a 34% overall yield. We also developed a unique compound 2 by a cyclization reaction from the cyanoethylation of compound 1, which is an intermediate step in the synthesis of Aspidospermidine. The parent compound of Aspidospermidine alkaloids, comprise a large family of diverse structures. As a result, we obtained octahydropyrido[3,2-c]carbazole (6)and the proposed method may be applicable to other alkaloids. All quantum chemical calculations of the cis-4a-Ethyl-1-(2-hydroxyethyl)-2,3,4,4a,5,6,7,11c-octahydro-1H-pyrido[3,2-c]carbazole have been performed with the DFT/B3LYP and HF methods by using the Gaussian 09W software package. The most stable conformer obtained from the Potential Energy Surface (PES) scan analysis at the B3LYP/6-31G** level of theory in the gas phase was used as the starting structure of the title compound to further computational analysis. The Natural Bond Orbital (NBO) and NLO analyses were performed to evaluate the intra-molecular interactions contributing to the molecular stability and to predict the optical properties of the title compound, respectively. Gauge-Independent Atomic Orbital (GIAO) approach was used to determine the 1H and 1C NMR chemical shifts of the title compound by subtracting the shielding constants of TMS at both methods. The calculated vibrational frequencies of the title compound were assigned by using the VEDA program and were scaled down by using the scaling factor 0.9668 for B3LYP/6-311++G(d, p) and 0.9050 for HF/6-311++G(d, p) to improve the calculated vibrational frequencies. The FMO (frontier molecular orbital) analysis was evaluated to predict the chemical and physical properties of the title compound and the HOMO, LUMO, and MEP diagrams were visualized by GaussView 4.1 program to present the reactive site of the title compound.

  16. Mechanochemical synthesis of 1-stanna-2,3-dicarba-closo-dodecaborane SnB9C2H11

    International Nuclear Information System (INIS)

    Volkov, V.V.; Myakishev, K.G.; Solomatina, L.Ya.

    1990-01-01

    The possibility of synthesis of 1-stanna-2, 3-dicarba-dodecaborane (2), SnB 9 C 2 H 11 by the mechanical activation of solid mixtures of CsB 9 C 2 H 12 , NaH and SnCl 2 has been studied. These solid phase mechano-chemical reactions were performed in vacuum vibration mills without any liquid solvents at room temperature. Crystalline SnB 9 C 2 H 11 was produced by sublimation in vacuum at 140 deg C. Yioeld of the sublimate was 3-6%

  17. Preparation of [[sup 11]C]diethyl oxalate and [[sup 11]C]oxalic acid and demonstration of their use in the synthesis of [[sup 11]C]-2,3-dihydroxyquinoxaline

    Energy Technology Data Exchange (ETDEWEB)

    Thorell, J -O; Stone-Elander, S [Karolinska Pharmacy, Stockholm (Sweden) Karolinska Hospital and Institute, Stockholm (Sweden). Dept. of Clinical Neurophysiology; Elander, N [Manne Siegbahn Inst. of Physics, Stockholm (Sweden)

    1993-11-01

    A method for the production of two new carbon-11 labelled difunctional radiolabelling precursors, [[sup 11]C]diethyl oxalate,2, and [[sup 11]C]oxalic acid, 3 is described. Methyl chloroformate was reacted with no-carrier-added [[sup 11]C]cyanide to generate the intermediate nitrile, methyl [[sup 11]C]cyanoformate. Alcoholysis with HC1 in ethanol generated 2, which could subsequently be converted to 3 with aqueous acid. The total time of preparation from end-or-trapping of [[sup 11]C]cyanide was 6-7 min using combined microwave and thermal treatment or, by exclusively thermal treatment, 15 and 20 min for 2 and 3, respectively. The radiochemical conversion of [[sup 11]C]cyanide to 2 and 3 was [approx] 80% and [approx] 70%, respectively. Both 2 and 3 were used in a model reaction with 1,2-phenylenediamine to synthesize the heterocyclic compound, 2,3-dihydroxyquinoxaline, a basic structural unit in antagonists for the excitatory amino acid receptor system. (Author).

  18. Aziridines in the synthesis of 11C- and 18F-labelled compounds

    International Nuclear Information System (INIS)

    Gillings, N.M.

    1998-01-01

    Racemic [4- 11 C]aspartic acid, [4- 11 C]asparagine and 2,4-diamino[4- 11 C]butyric acid were synthesised by the ring-opening of an N-activated aziridine-2-carboxylate with 11 C]cyanide, followed by preparative HPLC and hydrolysis/reduction. These labelled amino acids arise from nucleophilic attack at the β-carbon of the aziridine ring. A radioactive by-product of ca. 25% was attributed to the product of α-attack. Several N-activated 2-aryl aziridines were synthesised for the attempted synthesis of β-[ 18 F] fluorophenylalanine and β-[ 18 F]fluorodopa. Ring-opening with [ 18 F]fluoride showed no evidence of β-fluorinated products and it is proposed that attack occurs exclusively at the α-carbon, giving the corresponding α-[ 18 F]fluoro-β-amino acids. Further evidence for this was the reaction of the β-unsubstituted N-activated aziridine-2-carboxylate with [ 18 F]fluoride. This reaction was totally regiospecific and afforded exclusively the α-substituted product, α-[ 18 F]fluoro-β-alanine. Aziridine precursors were resolved by chiral HPLC. On labelling the chiral aziridines, however, racemic 11 C- and 18 F-labelled amino acids were obtained. This was attributed to racemisation of the initially formed ring-opened products. The use of [ 11 C]methyl lithium as a nucleophile for aziridine ring-opening was investigated. Reaction was expected to occur at low temperature, thus potentially avoiding racemisation. No products corresponding to aziridine ring-opening with [ 11 C]methyl lithium were, however, observed. A difluorinated analogue of amphetamine was synthesised by fluorination of an azirine (via an aziridine). This racemic compound was resolved as its chiral tartarate salts and subsequently labelled by methylation with [ 11 C]methyl iodide, giving the novel compound β, β-difluoro[N-methyl- 11 C]methamphetamine in high specific activity for in vivo binding studies using positron emission tomography. The non-radioactive reference compound was also

  19. 1-Benzylimidazolium hexafluorophosphate–1-benzylimidazole (1/1

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    Qing-Xiang Liu

    2008-02-01

    Full Text Available In the title compound, C10H11N2+·PF6−·C10H10N2, the H atom involved in protonation is disordered equally between the cation and the neutral molecule. The dihedral angle between the phenyl and imidazole rings is 82.6 (2°. In the crystal structure, there are head-to-tail π–π stacking interactions between imidazole rings; the interplanar separation is 3.295 (1 Å and the centroid–centroid separation is 3.448 (3 Å. In the centrosymmetric anion, two F atoms are disordered over two positions; the refined site-occupancy factors are 0.855 (11 and 0.145 (11.

  20. 2-Ethyl-6-(2-pyridyl-5,6,6a,11b-tetrahydro-7H-indeno[2,1-c]quinoline

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    Alexander Briceño

    2010-03-01

    Full Text Available The title compound, C23H22N2, was obtained using the three-component imino Diels–Alder reaction via a one-pot condensation between anilines, α-pyridinecarboxyaldehyde and indene using BF3·OEt2 as the catalyst. The molecular structure reveals the cis-form as the unique diastereoisomer. The crystal structure comprises one-dimensional zigzag ribbons connected via N—H...N hydrogen bonds. C—H...π interactions also occur.

  1. Development of [11C]/[3H]THK-5351 – A potential novel carbon-11 tau imaging PET radioligand

    International Nuclear Information System (INIS)

    Stepanov, Vladimir; Svedberg, Marie; Jia, Zhisheng; Krasikova, Raisa; Lemoine, Laetitia; Okamura, Nobujuki; Furumoto, Shozo; Mitsios, Nicholas; Mulder, Jan; Långström, Bengt; Nordberg, Agneta; Halldin, Christer

    2017-01-01

    Introduction: Due to the rise in the number of patients with dementia the imperative for finding new diagnostic and treatment options becomes ever more pressing. While significant progress has been made in PET imaging of Aβ aggregates both in vitro and in vivo, options for imaging tau protein aggregates selectively are still limited. Based on the work previously published by researchers from the Tohoku University, Japan, that resulted in the development of [ 18 F]THK-5351, we have undertaken an effort to develop a carbon-11 version of the identical structure - [ 11 C]THK-5351. In parallel, THK-5351 was also labeled with tritium ([ 3 H]THK-5351) for use in in vitro autoradiography (ARG). Methods: The carbon-11 labeling was performed starting with di-protected enantiomeric pure precursor - tert-butyl 5-(6-((2S)-3-fluoro-2-(tetrahydro-2H-pyran-2-yloxy)propoxy)quinolin-2-yl) pyridin-2-yl carbamate, which was reacted with [ 11 C]MeI, using DMF as the solvent and NaH as base, followed by deprotection with trifluoroacetic acid/water mixture, resulting in enantiomerically pure carbon-11 radioligand, [ 11 C]THK-5351 - (S)-1-fluoro-3-(2-(6-([ 11 C]methylamino)pyridin-3-yl)quinolin-6-yloxy) propan-2-ol. Tritium labeling and purification of [ 3 H]THK-5351 were undertaken using similar approach, resulting in [ 3 H]THK-5351 with RCP >99.8% and specific radioactivity of 1.3 GBq/μmol. Results: [ 11 C]THK-5351 was produced in good yield (1900 ± 355 MBq), specific radioactivity (SRA) (361 ± 119 GBq/μmol at EOS + 20 min) and radiochemical purity (RCP) (>99.8%), with enantiomeric purity of 98.7%. [ 3 H]THK-5351 was evaluated for ARG of tau binding in post-mortem human brain tissue using cortical sections from one AD patient and one control subject. [ 3 H]THK-5351 binding density was higher in the AD patient compared to the control subject, the binding was displaced by unlabeled THK-5351 confirming specific [ 3 H]THK-5351 binding.

  2. X-ray and Hydrogen-bonding Properties of 1-((1H-benzotriazol-1-ylmethylnaphthalen-2-ol

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    Jaime Ríos-Motta

    2009-03-01

    Full Text Available The solid state structure of 1-((1H-benzotriazol-1-ylmethylnaphthalen-2-ol, C17H13N3O, shows that this Mannich base crystallizes forming intermolecular N···HO hydrogen bonds, rather than intramolecular ones. Factors contributing to this choice of hydrogen-bonding mode are discussed. The compound crystallizes in the monoclinic system, P21/c space group, with lattice constants: a = 11.7934(9 Å, b = 14.3002(14 Å, c = 8.4444(8 Å, β = 106.243(5 deg, V = 1367.3(2 Å3, Z = 4, F(000 = 576, R1 = 6.96%, wR2 = 11.4%.

  3. Crystal structures of the 2:2 complex of 1,1′-(1,2-phenylenebis(3-m-tolylurea and tetrabutylammonium chloride or bromide

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    Chao Huang

    2017-09-01

    Full Text Available The title compounds, tetrabutylammonium chloride–1,1′-(1,2-phenylenebis(3-m-tolylurea (1/1, C16H36N+·Cl−·C22H22N4O2 or [(n-Bu4N+·Cl−(C22H22N4O2] (I and tetrabutylammonium bromide–1,1′-(1,2-phenylenebis(3-m-tolylurea (1/1, C16H36N+·Br−·C22H22N4O2 or [(n-Bu4N+·Br−(C22H22N4O2] (II, both comprise a tetrabutylammonium cation, a halide anion and an ortho-phenylene bis-urea molecule. Each halide ion shows four N—H...X (X = Cl or Br interactions with two urea receptor sites of different bis-urea moieties. A crystallographic inversion centre leads to the formation of a 2:2 arrangement of two halide anions and two bis-urea molecules. In the crystals, the dihedral angle between the two urea groups of the bis-urea molecule in (I [defined by the four N atoms, 165.4 (2°] is slightly smaller than that in (II [167.4 (2°], which is probably due to the smaller ionic radius of chloride compared to bromide.

  4. Optimization of the radiosynthesis of the Alzheimer tracer 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB)

    International Nuclear Information System (INIS)

    Philippe, C.; Haeusler, D.; Mitterhauser, M.; Ungersboeck, J.; Viernstein, H.; Dudczak, R.; Wadsak, W.

    2011-01-01

    [ 11 C]PIB is still the standard PET compound for Alzheimer imaging targeting beta-amyloid plaques. We aimed to establish a fully-automated procedure for the synthesis and purification of [ 11 C]PIB with a high degree of reliability and improved specific activity as well as a suitable and fast quality control assay. The optimum reaction conditions were 75 deg. C, 4 mg/mL precursor yielding at 48.0±2.7% (EOS, based on [ 11 C]CH 3 OTf, corrected for decay), 183±14 GBq/μmol specific activity and >99% radiochemical purity. Time consumption was kept to a minimum (40 min from EOB) and overall yields were enough to serve 2 consecutive patients with a single preparation. - Highlights: → Optimized radiosynthesis of [ 11 C]PIB in 40 min. → Optimum reaction conditions were 75 deg. C and 4 mg/mL precursor. → Radiochemical yields were 4.2±1.1 GBq. → The specific activity was 183±14 GBq/μmol.

  5. 5,11-Ditosyl-5H,11H-dibenzo[b,f][1,5]diazo-cine-6,12-dione acetic acid hemisolvate.

    Science.gov (United States)

    Abbassi, Najat; Bassou, Oulemda; Rakib, El Mostapha; Saadi, Mohamed; El Ammari, Lahcen

    2013-04-01

    The mol-ecular structure of the title compound, C28H22N2O6S2·0.5CH3COOH, is built up from three fused rings, two six and one eight membered. The eight-membered ring shows a boat conformation and the dihedral angle between the two benzene groups attached thereto is 66.43 (11)°, resulting in a V-shaped geometry. Two tosyl substituents are bound to the N atoms. The planes through the tolyl rings are roughly perpendicular, as indicated by the dihedral angle of 82.44 (12)°. In the crystal, the mol-ecule and its inversion-related symmetry-equivalent are linked to the acetic acid solvent mol-ecule by non-classical O-H⋯O and C-H⋯O hydrogen bonds. Two half-occupied acetic acid solvent mol-ecules are disordered at the same site and linked by a center of symmetry.

  6. Crystal strucutre of rac-methyl (11aR*,12S*,13R*,15aS*,15bS*-11-oxo-11,11a,12,13-tetrahydro-9H,15bH-13,15a-epoxyisoindolo[1,2-c]pyrrolo[1,2-a][1,4]benzodiazepine-12-carboxylate

    Directory of Open Access Journals (Sweden)

    Vladimir P. Zaytsev

    2014-12-01

    Full Text Available The title compound, C21H18N2O4, obtained as a racemate, contains a novel heterocyclic system, viz. isoindolo[1,2-c]pyrrolo[1,2-a][1,4]benzodiazepine. The central diazepane ring has a distorted boat conformation with two phenylene-fused and one methine C atom deviating by 0.931 (1, 0.887 (1 and 0.561 (1 Å, respectively, from the mean plane of the rest of the ring. The γ-lactone ring has an envelope conformation, with the C atom opposite to amide bond deviating by 0.355 (1 Å from its plane. In the crystal, molecules form centrosymmetric dimers through pairs of C—H...O hydrogen bonds.

  7. Synthesis and pharmacological characterization of a new PET ligand for the serotonin transporter: [{sup 11}C]5-bromo-2-[2-(dimethylaminomethylphenylsulfanyl)]phenylamine ([{sup 11}C]DAPA)

    Energy Technology Data Exchange (ETDEWEB)

    Huang Yiyun E-mail: hh285@columbia.edu; Hwang, D.-R.; Zhu Zhihong; Bae, S.-A.; Guo Ningning; Sudo, Yasuhiko; Kegeles, Lawrence S.; Laruelle, Marc

    2002-10-01

    A new PET radioligand for the serotonin transporter (SERT), [{sup 11}C]-5-bromo-2-[2-(dimethylaminomethylphenylsulfanyl)]phenylamine ([{sup 11}C]DAPA (10), was synthesized and evaluated in vivo in rats and baboons. [{sup 11}C]DAPA (10) was prepared from its monomethylamino precursor 8 by reaction with high specific activity [{sup 11}C]methyl iodide. Radiochemical yield was 24{+-}5% based on [{sup 11}C]methyl iodide at end of bombardment (EOB, n=10) and specific activity was 1553{+-}939 Ci/mmol at end of synthesis (EOS, n=10). Binding assays indicated that [{sup 11}C]DAPA displays high affinity (Ki 1.49{+-}0.28 nM for hSERT) and good selectivity for the SERT in vitro. Biodistribution studies in rats indicated that [{sup 11}C]DAPA enters into the brain readily and localizes in brain regions known to contain high concentrations of SERT, such as the thalamus, hypothalamus, frontal cortex and striatum. Moreover, such binding in SERT-rich regions of the brain are blocked by pretreatment with either the selective serotonin reuptake inhibitor (SSRI) citalopram and by the cold compound itself, demonstrating that [{sup 11}C]DAPA binding in the rat brain is saturable and specific to SERT. Imaging experiments in baboons indicated that [{sup 11}C]DAPA binding is consistent with the known distribution of SERT in the baboon brain, with highest levels of radioactivity detected in the midbrain and thalamus, intermediate levels in the hippocampus and striatum, and lower levels in the cortical regions. Pretreatment of the baboon with citalopram 10 min before radioactivity injection blocked the binding of [{sup 11}C]DAPA in all brain regions that contain SERT. Kinetic analysis revealed that, in all brain regions examined, [{sup 11}C]DAPA specific to nonspecific distribution volume ratios (V{sub 3}'') are higher than [{sup 11}C](+)-McN 5652 and similar to [{sup 11}C]DASB. In summary, [{sup 11}C]DAPA appears to be a promising radioligand suitable for the visualization of SERT

  8. Aziridines in the synthesis of {sup 11}C- and {sup 18}F-labelled compounds

    Energy Technology Data Exchange (ETDEWEB)

    Gillings, N.M

    1998-07-01

    Racemic [4-{sup 11}C]aspartic acid, [4-{sup 11}C]asparagine and 2,4-diamino[4-{sup 11}C]butyric acid were synthesised by the ring-opening of an N-activated aziridine-2-carboxylate with [{sup 11}C]cyanide, followed by preparative HPLC and hydrolysis/reduction. These labelled amino acids arise from nucleophilic attack at the {beta}-carbon of the aziridine ring. A radioactive by-product of ca. 25% was attributed to the product of {alpha}-attack. Several N-activated 2-aryl aziridines were synthesised for the attempted synthesis of {beta}-[{sup 18}F] fluorophenylalanine and {beta}-[{sup 18}F]fluorodopa. Ring-opening with [{sup 18}F]fluoride showed no evidence of {beta}-fluorinated products and it is proposed that attack occurs exclusively at the {alpha}-carbon, giving the corresponding {alpha}-[{sup 18}F]fluoro-{beta}-amino acids. Further evidence for this was the reaction of the {beta}-unsubstituted N-activated aziridine-2-carboxylate with [{sup 18}F]fluoride. This reaction was totally regiospecific and afforded exclusively the {alpha}-substituted product, {alpha}-[{sup 18}F]fluoro-{beta}-alanine. Aziridine precursors were resolved by chiral HPLC. On labelling the chiral aziridines, however, racemic {sup 11}C- and {sup 18}F-labelled amino acids were obtained. This was attributed to racemisation of the initially formed ring-opened products. The use of [{sup 11}C]methyl lithium as a nucleophile for aziridine ring-opening was investigated. Reaction was expected to occur at low temperature, thus potentially avoiding racemisation. No products corresponding to aziridine ring-opening with [{sup 11}C]methyl lithium were, however, observed. A difluorinated analogue of amphetamine was synthesised by fluorination of an azirine (via an aziridine). This racemic compound was resolved as its chiral tartarate salts and subsequently labelled by methylation with [{sup 11}C]methyl iodide, giving the novel compound {beta}, {beta}-difluoro[N-methyl-{sup 11}C]methamphetamine in high

  9. Reactions of 11C recoil atoms in the systems H2O-NH3, H2O-CH4 and NH3-CH4

    International Nuclear Information System (INIS)

    Nebeling, B.

    1988-11-01

    In this study the chemical reactions of recoil carbon 11 in the binary gas mixtures H 2 O-NH 3 , H 2 O-CH 4 and NH 3 -CH 4 in different mixing ratios as well as in solid H 2 O and in a solid H 2 O-NH 3 mixture were analyzed in dependence of the dose. The analyses were to serve e.g. the simulation of chemical processes caused by solar wind, solar radiation and cosmic radiation in the coma and core of comets. They were to give further information about the role of the most important biogeneous element carbon, i.e. carbon, in the chemical evolution of the solar system. Besides the actual high energy processes resulting in the so-called primary products, also the radiation-chemical changes of the primary products were also observed in a wide range of dosing. The generation of the energetic 11 C atoms took place according to the target composition by the nuclear reactions 14 N(p,α) 11 C, 12 C( 3 He,α) 11 C or the 16 O(p,αpn) 11 C reaction. The identification of the products marked with 11 C was carried out by means of radio gas chromatography or radio liquid chromatography (HPLC). (orig./RB) [de

  10. Reaction of 11 C-benzoyl chlorides with metalloid reagents: 11 C-labeling of benzyl alcohols, benzaldehydes, and phenyl ketones from [11 C]CO.

    Science.gov (United States)

    Roslin, Sara; Dahl, Kenneth; Nordeman, Patrik

    2018-01-26

    In this article, we describe the carbon-11 ( 11 C, t 1/2  = 20.4 minutes) labeling of benzyl alcohols, benzaldehydes, and ketones using an efficient 2-step synthesis in which 11 C-carbon monoxide is used in an initial palladium-mediated reaction to produce 11 C-benzoyl chloride as a key intermediate. In the second step, the obtained 11 C-benzoyl chloride is further treated with a metalloid reagent to furnish the final 11 C-labeled product. Benzyl alcohols were obtained in moderated to high non-isolated radiochemical yields (RCY, 35%-90%) with lithium aluminum hydride or lithium aluminum deuteride as metalloid reagent. Changing the metalloid reagent to either tributyltin hydride or sodium borohydride, allowed for the reliable syntheses of 11 C-benzaldehydes in RCYs ranging from 58% to 95%. Finally, sodium tetraphenylborate were utilized to obtain 11 C-phenyl ketones in high RCYs (77%-95%). The developed method provides a new and efficient route to 3 different classes of compounds starting from aryl iodides or aryl bromides. Copyright © 2018 John Wiley & Sons, Ltd.

  11. 11 CFR 100.11 - State (2 U.S.C. 431(12)).

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false State (2 U.S.C. 431(12)). 100.11 Section 100.11 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) General Definitions § 100.11 State (2 U.S.C. 431(12)). State means each State of the United States, the District of...

  12. C-11 cyanide production system

    Science.gov (United States)

    Kim, Dohyun; Alexoff, David; Kim, Sung Won; Hooker, Jacob M.; Ferrieri, Richard A.

    2017-11-21

    A method for providing .sup.11C-labeled cyanides from .sup.11C labeled oxides in a target gas stream retrieved from an irradiated high pressure gaseous target containing O.sub.2, wherein .sup.11C labeled oxides are reduced with H.sub.2 in the presence of a nickel catalyst under a pressure and a temperature sufficient to form a product stream comprising at least about 95% .sup.11CH.sub.4, the .sup.11CH.sub.4 is then combined with an excess of NH.sub.3 in a carrier/reaction stream flowing at an accelerated velocity and the combined .sup.11CH4 carrier/reaction stream is then contacted with a platinum (Pt) catalyst particulate supported on a substantially-chemically-nonreactive heat-stable support at a temperature of at least about 900.degree. C., whereby a product stream comprising at least about 60% H.sup.11CN is provided in less than 10 minutes from retrieval of the .sup.11C labeled oxide.

  13. 1,1′-Binaphthyl-2,2′-dicarboxylic acid–urea (1/1

    Directory of Open Access Journals (Sweden)

    Edwin Weber

    2008-10-01

    Full Text Available In the title co-crystal, C22H14O4·CH4N2O, the 1,1′-binaphthyl-2,2′-dicarboxylic acid (BNDA and urea molecules are connected via a system of hydrogen bonds into a chiral two-dimensional polymeric structure parallel to the (001 plane. As the crystal is centrosymmetric, it consists of alternately stacked BNDA–urea layers of opposite chirality. The urea H atoms trans to the C=O group are bonded in a chelating mode [R12(6] to the carbonyl O atom from one of the carboxylic acid groups which, in turn, acts as the donor of an O—H...O hydrogen bond to another urea molecule. The [010] chains thus formed are further connected via an R22(8 hydrogen-bond motif formed between urea and the second carboxylic acid group of BNDA.

  14. (S-2-(4-Chlorobenzoyl-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH-dione—Synthesis and Crystallographic Studies

    Directory of Open Access Journals (Sweden)

    Adam Mieczkowski

    2017-10-01

    Full Text Available (S-2-(4-Chlorobenzoyl-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH-dione was obtained in a three-step, one-pot synthesis, starting from optically pure (S-2-piperazine carboxylic acid dihydrochloride. Selective acylation of the β-nitrogen atom followed by condensation with isatoic anhydride and cyclization with HATU/DIPEA to a seven-member benzodiazepine ring, led to the tricyclic benzodiazepine derivative. Crystallographic studies and initial biological screening were performed for the title compound.

  15. 2,2-Dimethyl-2,3-dihydropyrano[2,3-a]carbazol-4(11H-one

    Directory of Open Access Journals (Sweden)

    Makuteswaran Sridharan

    2008-11-01

    Full Text Available The title compound, C17H15NO2, was prepared from 1-hydroxycarbazole and 3,3-dimethylacrylic acid with a mixture of AlCl3 and POCl3 as the cyclization catalyst. Owing to the presence of the –CMe2– group, the molecule is not quite planar. In the crystal structre, strong N—H...O hydrogen bonds and weaker C—H...π interactions occur, and a slipped π–π stacking interaction [centroid–centroid separation = 3.8425 (8 Å] is also observed.

  16. 5,11-Ditosyl-5H,11H-dibenzo[b,f][1,5]diazo­cine-6,12-dione acetic acid hemisolvate

    Science.gov (United States)

    Abbassi, Najat; Bassou, Oulemda; Rakib, El Mostapha; Saadi, Mohamed; El Ammari, Lahcen

    2013-01-01

    The mol­ecular structure of the title compound, C28H22N2O6S2·0.5CH3COOH, is built up from three fused rings, two six and one eight membered. The eight-membered ring shows a boat conformation and the dihedral angle between the two benzene groups attached thereto is 66.43 (11)°, resulting in a V-shaped geometry. Two tosyl substituents are bound to the N atoms. The planes through the tolyl rings are roughly perpendicular, as indicated by the dihedral angle of 82.44 (12)°. In the crystal, the mol­ecule and its inversion-related symmetry-equivalent are linked to the acetic acid solvent mol­ecule by non-classical O—H⋯O and C—H⋯O hydrogen bonds. Two half-occupied acetic acid solvent mol­ecules are disordered at the same site and linked by a center of symmetry. PMID:23634138

  17. Synthesis and evaluation of (S)-4-(3-(2'-[C-11]isopropylamino)-2-hydroxy-propoxy)-2H-benzimidazol-2-one ((S)-[C-11]CGP 12388) and (S)-4-(3-((1'-[F-18]-fluoroisopropyl)amino)-2-hydroxypropoxy)-2H-benzimidazol-2-one ((S)-[F-18]Fluoro-CGP 12388) for visualization of beta-adrenoceptors with positron emission tomography

    NARCIS (Netherlands)

    Elsinga, PH; vanWaarde, A; Jaeggi, KA; Schreiber, G; Heldoorn, M; Vaalburg, W

    1997-01-01

    The beta-adrenoceptor antagonist (S)-[C-11]CGP 12177 (4-(3-(tert-butylamino)-2-hydroxypropoxy)- 2H-benzimidazol-2[C-11]-one) is a generally accepted radioligand for cardiac and pulmonary PET studies. The synthesis of [C-11]CGP 12177 is a laborious and often troublesome procedure. Therefore, (S)-C GP

  18. Low-temperature heat capacity of Al(C11H19O2)3

    International Nuclear Information System (INIS)

    Bespyatov, Michael A.; Chernyaikin, Ivan S.; Naumov, Viktor N.; Stabnikov, Pavel A.; Gelfond, Nikolay V.

    2014-01-01

    Highlights: • The temperature dependence of heat capacity of Al(C 11 H 19 O 2 ) 3 has been measured. • The experimental data were used to calculate standard thermodynamic functions. • The thermodynamic functions at 298.15 K are presented. - Abstract: The heat capacity of Al(C 11 H 19 O 2 ) 3 was measured by adiabatic-shield calorimetry in the temperature range 6–320 K; no transition or thermal anomalies were found. The thermodynamic functions (entropy, enthalpy, and reduced Gibbs free energy) at 298.15 K have been calculated using the obtained experimental heat capacity data. The obtained standard values are as follows: C° p,m = (882.3 ± 1.3) J mol −1 K −1 , Δ 0 298.15 S° m = J(980 ± 2) mol −1 K −1 , Δ 0 298.15 H° m = (145.1 ± 0.2) kJ mol −1 , Φ° m = (493.4 ± 1.7) J mol −1 K −1

  19. The 1:1 adduct of caffeine and 2-(1,3-dioxoisoindolin-2-ylacetic acid

    Directory of Open Access Journals (Sweden)

    Moazzam H. Bhatti

    2011-09-01

    Full Text Available In the crystal structure of the title adduct [systematic name: 2-(1,3-dioxoisoindolin-2-ylacetic acid–1,3,7-trimethyl-1,2,3,6-tetrahydro-7H-purine-2,6-dione (1/1], C8H10N4O2·C10H7NO4, the components are linked by an O—H...N hydrogen-bond and no proton transfer occurs.

  20. Catalytic conversion of 11CO2 and 11CO into synthesis precursors for 11C labelling

    International Nuclear Information System (INIS)

    Patt, J.T.

    1994-03-01

    The positron emitter carbon-11 (T 1/2 =20.3 min) is an ideal radio nuclide for tracers in positron emission tomography (PET). In this study catalytic methods for the synthesis of [ 11 C]alcohols have been investigated. The formation of [ 11 C]methanol has been studied on Pd/Al 2 O 3 and Cu/ZnO/Al 2 O 3 catalysts with respect to CO and CO 2 carrier addition to the synthesis gas. Carbon monoxide was identified as the precursor of methanol formation on the Pd/Al 2 O 3 -catalyst. In contrast on the Cu/ZnO/Al 2 O 3 -catalyst methanol was formed on a reaction pathway via an adsorbed CO 2 -species. A n.c.a.-[ 11 C]methanol synthesis basing on the Cu/ZnO/Al 2 O 3 -catalyst has been developed by substitution of the oxygen containing components CO and CO 2 in the synthesis gas by N 2 O. The radiochemical yield, the low selectivity of [ 11 C]methanol production and the rather slow kinetics of this process were arguments against the practical use of this process in the synthesis of 11 C-labelling agents. (orig.)

  1. Dopamine D2 receptor radiotracers [11C](+)-PHNO and [3H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo

    International Nuclear Information System (INIS)

    McCormick, Patrick N.; Kapur, Shitij; Seeman, Philip; Wilson, Alan A.

    2008-01-01

    Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [ 11 C](+)-PHNO ([ 11 C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [ 3 H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [ 11 C](+)-PHNO and [ 3 H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for 11 C and 3 H. The specific binding ratio {SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum)} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [ 11 C](+)-PHNO and [ 3 H]raclopride SBRs responded indistinguishably in terms of both ED 50 and Hill slope (e.g., (-)-NPA ED 50 values are 0.027 and 0.023 mg/kg for [ 11 C](+)-PHNO and [ 3 H]raclopride, respectively). In response to AMPH challenge, [ 11 C](+)-PHNO and [ 3 H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [ 11 C](+)-PHNO- and [ 3 H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo applicability of the D2 two-state model, as described by in vitro binding experiments

  2. Synthesis of the Demospongic Compounds, (6Z, 11Z-Octadecadienoic Acid and (6Z, 11Z-Eicosadienoic Acid

    Directory of Open Access Journals (Sweden)

    V. R. Mamdapur

    1997-01-01

    Full Text Available A stereoselective synthesis of (6Z, 11Z-octadecadienoic acid (1 and (6Z, 11Z-eicosadienoic acid (2 from easily accessible pentane-1,5-diol (3 is described. Thus, compound 3 on pyranylation and oxidation gave the aldehyde 5 which was converted to the acid 7 by Wittig reaction with a suitable phosphorane. Its depyranylation and oxidation furnished the key aldehyde 9 which upon Wittig reaction with n-heptylidene and n-nonylidene phosphoranes, respectively followed by alkaline hydrolysis afforded the title acids.

  3. Caffeine-11C, ephedrine-11C and methylephedrine-11C: synthesis and distribution in mice

    International Nuclear Information System (INIS)

    Saji, Hideo; Ido, Tatsuo; Iwata, Ren; Suzuki, Kazutoshi; Tamate, Kazuhiko

    1978-01-01

    Caffeine, ephedrine and methylephedrine were labeled with carbon-11 by the action of methyliodide- 11 C on theophylline, norephedrine and ephedrine, respectively. Caffeine- 11 C was prepared in 44 min. with a radiochemical yield of 40%, ephedrine- 11 C in 45 min. with a 11% radiochemical yield and methylephedrine- 11 C in 36 min. with a 43% radiochemical yield. When injected in mice intravenously, these products show a high uptake in the liver, the kidney and the blood for caffeine- 11 C and in the liver and the kidney for ephedrine- 11 C and methylephedrine- 11 C. The brain uptake for these products was found to be 2.4 to 3.9% of the injected dose per gram at 5 min. after injection. These studies in mice have demonstrated that these products are potentially useful agents for the dynamic studies of the brain. (auth.)

  4. Photochemically activated antiviral halogenated 1,8-naphthalimides: synthesis of N,N'-bis-{2-[(5-bromo-2-[1-14C]hexyl-1H-benz[de]isoquinolin-1,3(2H)-dion-6-yl)amino]ethyl}hexanediamide

    International Nuclear Information System (INIS)

    Hayes, B.A.; Gupta, Surendra; Shaochieh Chang; Utecht, R.E.; Lewis, D.E.

    1996-01-01

    The synthesis of N,N'-bis-{2-[(5-bromo-2-[1- 14 C]hexyl-1H-benz[de]isoquinolin-1, 3(2H)-dion-6-yl)amino]ethyl}hexanediamide from 1-[1- 14 C]-hexylamine and 4-chloro-1,8-naphthalic anhydride is described. The anhydride is first converted to the 4-chloro-n-[1- 14 C]hexyl-1,8-naphthalimide by condensation with 1-[1- 14 C]-hexylamine, and the chlorine is then displaced with ethylenediamine to give the 4-(2-aminoethylamino-N-[1- 14 C]hexyl-1,8-naphthalimide. Coupling of this monomeric naphthalimide with adipoyl chloride affords the dimeric naphthalimide which is brominated regiospecifically with elemental bromine in carbon tetrachloride to afford the title compound. (author)

  5. A simple, versatile, low-cost and remotely operated apparatus for [11C]acetate, [11C]choline, [11C]methionine and [11C]PIB synthesis

    International Nuclear Information System (INIS)

    Cheung Manki; Ho Chilai

    2009-01-01

    A simple, efficient and remotely operated synthesis apparatus for carrying out routine [ 11 C]carboxylation, on-column and bubbling [ 11 C]methylation was essential for reliable, day-to-day production of [ 11 C]-labelled PET radiopharmaceuticals. We developed an in-house apparatus specifically applied to the synthesis of [ 11 C]acetate, [ 11 C]choline, [ 11 C]methionine and 2-(4'-N-[ 11 C]methylaminophenyl)-6-hydroxybenzothiazole ([ 11 C]PIB), where high radiochemical purity (≥97%) and moderate radiochemical yields (18% for [ 11 C]PIB, 41-55% for the others) could be achieved. These findings provided evidence that this was a fast, versatile and reliable apparatus suitable for a PET/CT centre with limited financial budget and hot cell space for synthesis of [ 11 C]-labelled radiopharmaceuticals

  6. Capturing [11C]CO2 for use in aqueous applications

    International Nuclear Information System (INIS)

    Vandehey, Nicholas T.; O’Neil, James P.

    2014-01-01

    We present a simple method for trapping [ 11 C]CO 2 gas and releasing it into a buffered solution using an ion-exchange cartridge. Sodium hydroxide cartridges captured >99% of [ 11 C]CO 2 following NaOH activation. A sodium bicarbonate solution eluted >99% of trapped radioactivity. Trapping [ 11 C]CO 2 directly in small volumes of several solutions was less effective than cartridge methods. The recommended methods allow for fast and simple production of highly concentrated carbon-11 containing aqueous solutions for use in filling phantoms, calibrating detectors, or (bio)geochemical experiments. - Highlights: • An ion exchange resin can trap [ 11 C]CO 2 gas and release it with saturated bicarbonate. • Elution from cartridge requires as little as 300 µL volume, with eluant at pH=10. • SPE trap-and-release provided better results than trapping in solution

  7. First line shape analysis and spectroscopic parameters for the ν11 band of 12C2H4

    KAUST Repository

    Es-sebbar, Et-touhami

    2016-08-11

    An accurate knowledge of line intensities, collisional broadening coefficients and narrowing parameters is necessary for the interpretation of high-resolution infrared spectra of the Earth and other planetary atmospheres. One of the most promising spectral domains for (C2H4)-C-12 monitoring in such environments is located near the 336 gm window, through its v(11) C-H stretching mode. In this paper, we report an extensive study in which we precisely determine spectroscopic parameters of (C2H4)-C-12 v(11) band at 297 +/- 1 K, using a narrow Difference-Frequency-Generation (DFG) laser with 10(-4) cm(-1) resolution. Absorption measurements were performed in the 2975-2980 cm(-1) spectral window to investigate 32 lines corresponding to where, J\\'ka\\',kc\\'<- Jka,kc, 5 <= J <= 7; 0.5 <= K-a <= 6 and 1 <= K-c <= 14. Spectroscopic parameters are retrieved using either Voigt or appropriate Galatry profile to simulate the measured (C2H4)-C-12 line shape. Line intensities along with self-broadening coefficients are reported for all lines. Narrowing coefficients for each isolated line are also derived. To our knowledge, the current study reports the first extensive spectroscopic parameter measurements of the (C2H4)-C-12 v(11) band in the 2975-2980 cm(-1) range. (C) 2016 Elsevier Ltd. All rights reserved.

  8. First line shape analysis and spectroscopic parameters for the ν11 band of 12C2H4

    KAUST Repository

    Es-sebbar, Et-touhami; Mantzaras, John; Benilan, Yves; Farooq, Aamir

    2016-01-01

    An accurate knowledge of line intensities, collisional broadening coefficients and narrowing parameters is necessary for the interpretation of high-resolution infrared spectra of the Earth and other planetary atmospheres. One of the most promising spectral domains for (C2H4)-C-12 monitoring in such environments is located near the 336 gm window, through its v(11) C-H stretching mode. In this paper, we report an extensive study in which we precisely determine spectroscopic parameters of (C2H4)-C-12 v(11) band at 297 +/- 1 K, using a narrow Difference-Frequency-Generation (DFG) laser with 10(-4) cm(-1) resolution. Absorption measurements were performed in the 2975-2980 cm(-1) spectral window to investigate 32 lines corresponding to where, J'ka',kc'<- Jka,kc, 5 <= J <= 7; 0.5 <= K-a <= 6 and 1 <= K-c <= 14. Spectroscopic parameters are retrieved using either Voigt or appropriate Galatry profile to simulate the measured (C2H4)-C-12 line shape. Line intensities along with self-broadening coefficients are reported for all lines. Narrowing coefficients for each isolated line are also derived. To our knowledge, the current study reports the first extensive spectroscopic parameter measurements of the (C2H4)-C-12 v(11) band in the 2975-2980 cm(-1) range. (C) 2016 Elsevier Ltd. All rights reserved.

  9. Synthesis of 2-iodo- and 2-phenyl-[11C]melatonin: potential PET tracers for melatonin binding sites

    International Nuclear Information System (INIS)

    Chen Jiajun; Fiehn-Schulze, Brita; Firnau, Guenter; Brough, Paul A.; Snieckus, Victor

    1998-01-01

    Two 11 C-labelled melatonin derivatives, 2-iodo-[ 11 C]melatonin (2-iodo-5-methoxy-N[ 11 C-acetyl]-tryptamine, an agonist) and 2-phenyl-[ 11 C]melatonin (2-phenyl-5-methoxy-N[ 11 C-acetyl]tryptamine, a putative antagonist) were synthesized from [ 11 C]carbon dioxide. The reaction sequence was common to both compounds and consisted of three steps: (i) carbonylation of methyl magnesium bromide with [ 11 C]carbon dioxide, (ii) conversion of the adduct to [ 11 C]acetyl chloride, (iii) acetylation of the amine precursors (2-iodo-5-methoxy-tryptamine or 2-phenyl-5-methoxy-tryptamine) with [ 11 C]acetyl chloride. The precursors were especially prepared. The radiochemical yield was 19% for 2-iodomelatonin and 32% for 2-phenymelatonin, based on [ 11 C]carbon dioxide; the specific activity ranged from 300 to 600 mCi/μmol. Both labelled 2-substituted-melatonins are intended to be used as radiotracers to study melatonin binding sites in man with positron emission tomography

  10. The synthesis of [1-11C]-butanol

    International Nuclear Information System (INIS)

    Helus, F.; Maier-Borst, W.; Oberdorfer, F.; Silvester, D.J.

    1982-01-01

    11 C-labelled butanol has been synthesised for use as a tracer in the assessment of regional blood supply for substrate utilisation in tumors. 11 CO 2 was produced by the 14 N(p,a) 11 C reactions in a cyclotron. 11 C-butanol was formed by the carboxylation of n-propyl magnesium chlorides with 11 CO 2 , and reduction of the resulting 11 C-butyric acid with LiAlH 4 . (U.K.)

  11. 45 CFR 1626.11 - H-2 agricultural workers.

    Science.gov (United States)

    2010-10-01

    ...) Other employment rights as provided in the worker's specific contract under which the nonimmigrant... 45 Public Welfare 4 2010-10-01 2010-10-01 false H-2 agricultural workers. 1626.11 Section 1626.11... ON LEGAL ASSISTANCE TO ALIENS § 1626.11 H-2 agricultural workers. (a) Nonimmigrant agricultural...

  12. Di-μ-iodido-bis{[(R-(+-2,2′-bis(diphenylphosphanyl-1,1′-binaphthyl-κ2P,P′]copper(I} 0.67-hydrate

    Directory of Open Access Journals (Sweden)

    Daniel Volz

    2012-04-01

    Full Text Available The structure of the title compound, [Cu2I2(C44H32P22]·0.67H2O, has been determined because of its interesting catalytic and optical features. The molecule, which has non-crystallographic C2-symmetry, consists of a core structure of two CuI ions, bridged by two iodide ions. Each CuI ion is also coordinated by one equivalent of the chiral bidentate (R-BINAP ligand [BINAP = 2,2′-bis(diphenylphosphanyl-1,1′-binaphthyl]. Thus, both cations show a distorted tetrahedral geometry being surrounded by two I atoms and two P atoms from the (R-BINAP ligands. The complex consists of isolated butterfly-shaped molecules featuring an angle of 146.11 (2° between adjacent CuI2 planes. The structure displays intramolecular C—H...I hydrogen bonding and contains disordered water. The absolute configuration of this chiral complex was determined by anomalous dispersion effects.

  13. 1-Propyl-1H-indole-2,3-dione

    Directory of Open Access Journals (Sweden)

    Fatima Zahrae Qachchachi

    2016-04-01

    Full Text Available In the title compound, C11H11NO2, the 1H-indole-2,3-dione unit is essentially planar, with an r.m.s. deviation of 0.0387 (13 Å. This plane makes a dihedral angle of 72.19 (17° with the plane of the propyl substituent. In the crystal, chains propagating along the b axis are formed through C—H...O hydrogen bonds.

  14. Novel routes to 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines and 5,6,9,10,11,11a-hexahydro-8H-pyrido[1,2-a]pyrrolo[2,1-c]pyrazines.

    Science.gov (United States)

    Katritzky, Alan R; Jain, Ritu; Xu, Yong-Jiang; Steel, Peter J

    2002-11-15

    Condensation reactions of benzotriazole and 2-(pyrrol-1-yl)-1-ethylamine (1) with formaldehyde and glutaric dialdehyde, respectively, afforded intermediates 2 and 6. Subsequent nucleophilic substitutions of the benzotriazole group in 2 and 6 with Grignard reagents, sodium cyanide, and sodium borohydride gave 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines 3a-e, 4, 5 and 5,6,9,10,11,11a-hexahydro-8H-pyrido[1,2-a]pyrrolo[2,1-c]pyrazines 7a-c, 8, 9, respectively, in good yields.

  15. Synthesis of (1-/sup 11/C)-butanol

    Energy Technology Data Exchange (ETDEWEB)

    Oberdorfer, F; Helus, F; Maier-Borst, W [Deutsches Krebsforschungszentrum, Heidelberg (Germany, F.R.); Silvester, D J [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit

    1982-09-20

    A method for carrier-free labelling of n-butanol with the positron emitting radionuclide carbon-11 (half-life 20.4 min) is described. Labelling was achieved by carboxylation of n-propyl magnesium chloride with /sup 11/C-labelled carbon dioxide and the subsequent reduction of the resulting free (1-/sup 11/C)-butyric acid with LiAlH/sub 4/ after hydrolysis of the Grignard complex. The procedure permits /sup 11/C-labelled butanol to be prepared in high activity and high radiochemical purity for in vivo biological studies only 25 min after the start of carboxylation of the Grignard compound. Gas chromatography and HPLC were used to assess the purity of the product. To maintain carrier-free conditions, atmospheric carbon dioxide was rigorously excluded from all reagents and every parts of the apparatus.

  16. The synthesis of [1-11C]-butanol

    International Nuclear Information System (INIS)

    Oberdorfer, F.; Helus, F.; Maier-Borst, W.; Silvester, D.J.

    1982-01-01

    A method for carrier-free labelling of n-butanol with the positron emitting radionuclide carbon-11 (half-life 20.4 min) is described. Labelling was achieved by carboxylation of n-propyl magnesium chloride with 11 C-labelled carbon dioxide and the subsequent reduction of the resulting free [1- 11 C]-butyric acid with LiAlH 4 after hydrolysis of the Grignard complex. The procedure permits 11 C-labelled butanol to be prepared in high activity and high radiochemical purity for in vivo biological studies only 25 min after the start of carboxylation of the Grignard compound. Gas chromatography and HPLC were used to assess the purity of the product. To maintain carrier-free conditions, atmospheric carbon dioxide was rigorously excluded from all reagents and every parts of the apparatus. (author)

  17. 3-Ethyl-4-[(E-(4-fluorobenzylideneamino]-1H-1,2,4-triazole-5(4H-thione

    Directory of Open Access Journals (Sweden)

    Alphonsus D'souza

    2012-05-01

    Full Text Available In the title compound, C11H11FN4S, the dihedral angle between the 1,2,4-triazole ring and the benzene ring is 25.04 (12° and an intramoleuclar C—H...S interaction leads to an S(6 ring. In the crystal, inversion dimers linked by pairs of N—H...S hydrogen bonds generate R22(8 loops.

  18. Triosmium cluster compounds containing isocyanide and hydride ligands. Crystal and molecular structure of (μ-H)(μ-eta1-C==N(H)(t-C4H9))Os3(CO)10

    International Nuclear Information System (INIS)

    Adams, R.D.; Golembeski, N.M.

    1979-01-01

    The crystal and molecular structure of the compound (μ-H)(μ-eta 1 -C==N(H)(t-C 4 H 9 ))Os 3 (CO) 10 has been determined by X-ray crystallographic methods. The compound crystallizes in the centrosymmetric monoclinic space group P2 1 /n[C/sub 2h/ 5 ]:a = 13.651 (4) A, b = 9.156 (4) A, c = 18.275 (5) A, β = 111.42 (2) 0 , V = 2126.3 (25) A 3 , Z = 4, rho/sub calcd/ = 2.92 g cm -3 . A uniform triangular cluster of three osmium atoms contains ten linear carbonyl groups and a μ-eta 1 -C==N(H)(t-C 4 H 9 ) iminyl ligand. The carbon atom of the iminyl ligand symmetrically bridges one osmium-osmium bond, as is shown by the internuclear separations Os(2)-C(11) = 2.066 (8) A and Os(3)-C(11) = 2.043 (8) A. The iminyl bond, C(11)-N, is double with the C-N distance being 1.298 (10) A

  19. 2-(1,3-Dioxoisoindolin-2-ylacetic acid–N′-[(E-2-methoxybenzylidene]pyridine-4-carbohydrazide (1/1

    Directory of Open Access Journals (Sweden)

    Shaaban K. Mohamed

    2012-08-01

    Full Text Available In the title 1:1 cocrystal, C10H7NO4·C14H13N3O2, molecules are linked by intermolecular C—H...O, N—H...O and O—H...N hydrogen bonds, forming a three-dimensional network. In addition, π–π stacking interactions [with centroid–centroid distances of 3.5723 (19 and 3.6158 (18 Å] are observed.

  20. Crystal structure of 5-{4′-[(2-{2-[2-(2-ammonioethoxyethoxy]ethoxy}ethylcarbamoyl]-4-methoxy-[1,1′-biphenyl]-3-yl}-3-oxo-1,2,5-thiadiazolidin-2-ide 1,1-dioxide: a potential inhibitor of the enzyme protein tyrosine phosphatase 1B (PTP1B

    Directory of Open Access Journals (Sweden)

    Kasi Viswanatharaju Ruddraraju

    2015-04-01

    Full Text Available The title compound, C24H32N4O8S, (I, crystallizes as a zwitterion. The terminal amine N atom of the [(2-{2-[2-(2-ammonioethoxyethoxy]ethoxy}ethylcarbamoyl] side chain is protonated, while the 1,2,5-thiadiazolidin-3-one 1,1-dioxide N atom is deprotonated. The side chain is turned over on itself with an intramolecular N—H...O hydrogen bond. The 1,2,5-thiadiazolidin-3-one 1,1-dioxide ring has an envelope conformation with the aryl-substituted N atom as the flap. Its mean plane is inclined by 62.87 (8° to the aryl ring to which it is attached, while the aryl rings of the biphenyl unit are inclined to one another by 20.81 (8°. In the crystal, molecules are linked by N—H...O and N—H...N hydrogen bonds, forming slabs lying parallel to (010. Within the slabs there are C—H...O and C—H...N hydrogen bonds and C—H...π interactions present.

  1. Coordination compound of vanadyl with meta-nitrobenzoilgydrozine and polyedric closo-borate anions B11H11CH

    International Nuclear Information System (INIS)

    Safarov, Sh.S; Kayumov, A.; Mirsaidov, U.M.

    2005-01-01

    The new complex compound [V O(m-NBzH) 4 (H 2 O)](B 1 1H 1 1CH) 2 C 2 H 5 OH have been synthesised and their properties have investigated. The compound of medetomidine of meta-nitronbenzoilgydrazinum with the nitroge nium of amine group and external sphere of clozo-borate anions was defined by analysis of IR-spectra

  2. 2-(7-Methyl-1H-indol-3-ylacetonitrile

    Directory of Open Access Journals (Sweden)

    Yu-Hua Ge

    2012-01-01

    Full Text Available In the title compound, C11H10N2, the carbonitrile group is twisted away from the indole plane [Ccy—Cme—Car—Car = 66.6 (2°; cy = cyanide, me = methylene and ar = aromatic]. In the crystal, N—H...N hydrogen bonds link the molecules into C(7 chains propagating in the [001] direction.

  3. Synthesis of racemic [3-11C]phenylalanine and [3-11C] DOPA

    International Nuclear Information System (INIS)

    Halldin, C.; Laangstroem, B.

    1984-01-01

    The synthesis of racemic [3- 11 C]phenylalanine and [3- 11 C]DOPA is reported. The [ 11 C]benzaldehyde and [ 11 C]veratraldehyde prepared in a two-step reaction from the corresponding [ 11 C]acid salt and [ 11 C]alcohol, by means of selective oxidation with tetrabutylammonium hydrogen chromate, were reacted with 2-phenyl-5-oxazolone or 2-(4-chloro)phenyl-5-oxazolone in the presence of a tertiary amine to give the corresponding [α- 11 C]-4-arylene-2-aryl-5-oxazolones. Ring opening of these olefins, hydrogenation, and removal of protecting groups was carried out in one step using hydroiodic cid/phosphorus, with the production of the racemic [3- 11 C]amino acids in 8-30% radiochemical yield (starting with 11 CO 2 ) within 52-60 min (including LC separation). (author)

  4. 2-(2-Chlorophenyl-2,3-dihydroquinazolin-4(1H-one

    Directory of Open Access Journals (Sweden)

    Ming-Jian Li

    2009-09-01

    Full Text Available The title compound, C14H11ClN2O, was synthesized by the reaction of 2-chlorobenzaldehyde and 2-aminobenzamide in an ionic liquid. The pyrimidine ring adopts a skew-boat conformation and the two benzene rings make a dihedral angle of 87.1 (1°. In the crystal, N—H...O and C—H...N hydrogen bonding links the molecules along b.

  5. 1,3-Dimethyl-1H-indole-2-carbonitrile

    Directory of Open Access Journals (Sweden)

    Jiang-Sheng Li

    2009-08-01

    Full Text Available The title compound, C11H10N2, crystallizes with two molecules in the asymmetric unit, both of which are essentially planar (r.m.s. deviations = 0.014 and 0.016 Å. In the crystal, aromatic π–π stacking interactions occur [shortest centroid–centroid separation = 3.5569 (11 Å].

  6. Low-temperature heat capacities and standard molar enthalpy of formation of N-methylnorephedrine C211H17NO(s)

    Institute of Scientific and Technical Information of China (English)

    Di You-Ying; Wang Da-Qi; Shi Quan; Tan Zhi-Cheng

    2008-01-01

    This paper reports that low-temperature heat capacities of N-methylnorephedrine C11H17NO(s) have been mea- sured by a precision automated adiabatic calorimeter over the temperature range from T=78 K to T=400 K. A solid to liquid phase transition of the compound was found in the heat capacity curve in the temperature range of T=342- 364 K. The peak temperature, molar enthalpy and entropy of fusion of the substance were determined. The experimental values of the molar heat capacities in the temperature regions of T=78-342 K and T=364-400 K were fitted to two poly- nomial equations of heat capacities with the reduced temperatures by least squares method. The smoothed molar heat capacities and thermodynamic functions of N-methylnorephedrine C11H17NO(s) relative to the standard refer- ence temperature 298.15 K were calculated based on the fitted polynomials and tabulated with an interval of 5 K. The constant-volume energy of combustion of the compound at T=298.15 K was measured by means of an isoperibol preci- sion oxygen-bomb combustion calorimeter. The standard molar enthalpy of combustion of the sample was calculated. The standard molar enthalpy of formation of the compound was determined from the combustion enthalpy and other auxiliary thermodynamic data through a Hess thermochemical cycle.

  7. catena-Poly[[[aquasilver(I]-μ-1,1′-(butane-1,4-diyldi-1H-imidazole-κ2N3:N3′] hemi(biphenyl-4,4′-dicarboxylate dihydrate

    Directory of Open Access Journals (Sweden)

    Zheyu Zhang

    2009-12-01

    Full Text Available In the title compound, {[Ag(C10H14N4(H2O](C14H8O40.5·2H2O}n, the AgI ion is three-coordinated by two N atoms from two independent 1,1′-(butane-1,4-diyldi-1H-imidazole (BBI ligands and one water O atom in a distorted T-shaped coordination geometry. The biphenyl-4,4′-dicarboxylate (BPDC dianions do not coordinate to AgI ions but act as counter-ions. The AgI ions are linked by BBI ligands, forming a zigzag chain. These chains are linked into a two-dimensional supramolecular architecture by O—H...O hydrogen-bonding interactions between water molecules and carboxylate O atoms of the BPDC dianions.

  8. Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-11C-propyl]n-propylnorapomorphine

    International Nuclear Information System (INIS)

    Palner, Mikael; McCormick, Patrick; Gillings, Nic; Begtrup, Mikael; Wilson, Alan A.; Knudsen, Gitte M.

    2010-01-01

    Introduction: Several dopamine D 2 agonist radioligands have been used with positron emission tomography (PET), including [ 11 C-]-(-)-MNPA, [ 11 C-]-(-)-NPA and [ 11 C]-(+)-PHNO. These radioligands are considered particularly powerful for detection of endogenous dopamine release, but they either provide PET brain images with limited contrast or have affinity for both D 2 and D 3 receptors. We here present the carbon-11 radiolabeling and ex vivo evaluation of 2-Cl-(-)-NPA, a novel PET-tracer candidate with high in vitro D 2 /D 3 selectivity. Methods: 2-Cl-[ 11 C]-(-)-NPA and [ 11 C]-(-)-NPA were synthesized by a two step N-acylation-reduction process using [ 11 C]-propionyl chloride. Awake rats were injected with either tracer, via the tail vein. The rats were decapitated at various times, the brains were removed and quickly dissected, and plasma metabolites were measured. Radioligand specificity, and P-glycoprotein involvement in brain uptake, was also assessed. Results: 2-Cl-[ 11 C]-(-)-NPA and [ 11 C]-(-)-NPA were produced in high specific activity and purity. 2-Cl-[ 11 C]-(-)-NPA accumulated slower in the striatum than [ 11 C]-(-)-NPA, reaching maximum concentrations after 30 min. The maximal striatal uptake of 2-Cl-[ 11 C]-(-)-NPA (standard uptake value 0.72±0.24) was approximately half that of [ 11 C]-(-)-NPA (standard uptake value 1.37±0.18). Nonspecific uptake was similar for the two compounds. 2-Cl-[ 11 C]-(-)-NPA was metabolized quickly, leaving only 17% of the parent compound in the plasma after 30 min. The specific binding of 2-Cl-[ 11 C]-(-)-NPA was completely blocked and inhibition of P-glycoprotein did not alter the brain uptake. Conclusion: Ex vivo experiments showed, despite a favorable D 2 /D 3 selectivity, that 2-Cl-[ 11 C]-(-)-NPA is inferior to [ 11 C]-(-)-NPA as a PET tracer in rat, because of slower brain uptake and lower specific to nonspecific binding ratio.

  9. Vapor-Liquid Equilibrium in the Mixture 1,1-Difluoroethane C2H4F2 + C4H8 2-Methylpropene (EVLM1131, LB5730_E)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume A 'Binary Liquid Systems of Nonelectrolytes I' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Vapor-Liquid Equilibrium in the Mixture 1,1-Difluoroethane C2H4F2 + C4H8 2-Methylpropene (EVLM1131, LB5730_E)' providing data from direct measurement of pressure and mole fraction in vapor phase at variable mole fraction in liquid phase and constant temperature.

  10. 1,1′-Bicyclohexyl-1,1′-diyl 2,2′-bipyridine-3,3′-dicarboxylate

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2012-06-01

    Full Text Available The title compound, C24H26N2O4, lies about a crystallographic twofold rotation axis. The cyclohexane rings adopts a chair conformation. The two pyridine rings form a dihedral angle of 41.02 (4°. In the crystal, molecules are linked via C—H...O and C—H...N hydrogen bonds into a layer parallel to the bc plane.

  11. Rapid solid-phase extraction method to quantify [11C]-verapamil, and its [11C]-metabolites, in human and macaque plasma

    International Nuclear Information System (INIS)

    Unadkat, Jashvant D.; Chung, Francisco; Sasongko, Lucy; Whittington, Dale; Eyal, Sara; Mankoff, David; Collier, Ann C.; Muzi, Mark; Link, Jeanne

    2008-01-01

    Introduction: P-glycoprotein (P-gp), an efflux transporter, is a significant barrier to drug entry into the brain and the fetus. The positron emission tomography (PET) ligand, [ 11 C]-verapamil, has been used to measure in vivo P-gp activity at various tissue-blood barriers of humans and animals. Since verapamil is extensively metabolized in vivo, it is important to quantify the extent of verapamil metabolism in order to interpret such P-gp activity. Therefore, we developed a rapid solid-phase extraction (SPE) method to separate, and then quantify, verapamil and its radiolabeled metabolites in plasma. Methods: Using high-performance liquid chromatography (HPLC), we established that the major identifiable circulating radioactive metabolite of [ 11 C]-verapamil in plasma of humans and the nonhuman primate, Macaca nemestrina, was [ 11 C]-D-617/717. Using sequential and differential pH elution on C 8 SPE cartridges, we developed a rapid method to separate [ 11 C]-verapamil and [ 11 C]-D-617/717. Recovery was measured by spiking the samples with the corresponding nonradioactive compounds and assaying these compounds by HPLC. Results: Verapamil and D-617/717 recovery with the SPE method was >85%. When the method was applied to PET studies in humans and nonhuman primates, significant plasma concentration of D-617/717 and unknown polar metabolite(s) were observed. The SPE and the HPLC methods were not significantly different in the quantification of verapamil and D-617/717. Conclusions: The SPE method simultaneously processes multiple samples in less than 5 min. Given the short half-life of [ 11 C], this method provides a valuable tool to rapidly determine the concentration of [ 11 C]-verapamil and its [ 11 C]-metabolites in human and nonhuman primate plasma

  12. Synthesis and preliminary scintigraphic evaluation of in vivo distribution of 11C-hydroxyurea/isohydroxyurea and 11C-cyanate

    International Nuclear Information System (INIS)

    Winstead, M.B.; Chern, C.-I.; Lin, T.-H.; Khentigan, A.; Lamb, J.F.; Winchell, H.S.

    1978-01-01

    H 11 CN, produced directly from proton bombardment of 99% N 2 -1% H 2 [ 14 N(p, α) 11 C], was oxidized by KMn0 4 to 11 C-cyanate which was added to hydroxylamine at -5 to 0 0 C to yield a mixture of hydroxyurea and isohydroxyurea. Scintigraphic evaluation of in vivo distribution in a dog following administration of K0 11 CN showed diffuse whole-body distribution, apparently including brain, with greater activity seen in regions of the heart, liver, and kidneys. Similar evaluation of a dog given 11 C-hydroxyurea/isohydroxyurea showed early localization of activity in the region of the heart which appeared to be due to activity in the myocardium. However, tissue activity measured in rats after administration of this material failed to demonstrate concentration in the myocardium. (author)

  13. Quantification of myocardial blood flow with 11C-hydroxyephedrine dynamic PET: comparison with 15O-H2O PET.

    Science.gov (United States)

    Hiroshima, Yuji; Manabe, Osamu; Naya, Masanao; Tomiyama, Yuuki; Magota, Keiichi; Obara, Masahiko; Aikawa, Tadao; Oyama-Manabe, Noriko; Yoshinaga, Keiichiro; Hirata, Kenji; Kroenke, Markus; Tamaki, Nagara; Katoh, Chietsugu

    2017-12-21

    11 C-hydroxyephedrine (HED) PET has been used to evaluate the myocardial sympathetic nervous system (SNS). Here we sought to establish a simultaneous approach for quantifying both myocardial blood flow (MBF) and the SNS from a single HED PET scan. Ten controls and 13 patients with suspected cardiac disease were enrolled. The inflow rate of 11 C-HED (K1) was obtained using a one-tissue-compartment model. We compared this rate with the MBF derived from 15 O-H 2 O PET. In the controls, the relationship between K 1 from 11 C-HED PET and the MBF from 15 O-H 2 O PET was linked by the Renkin-Crone model. The relationship between K 1 from 11 C-HED PET and the MBF from 15 O-H 2 O PET from the controls' data was approximated as follows: K 1   =  (1 - 0.891 * exp(- 0.146/MBF)) * MBF. In the validation set, the correlation coefficient demonstrated a significantly high relationship for both the whole left ventricle (r = 0.95, P < 0.001) and three coronary territories (left anterior descending artery: r = 0.96, left circumflex artery: r = 0.81, right coronary artery: r =  0.86; P < 0.001, respectively). 11 C-HED can simultaneously estimate MBF and sympathetic nervous function without requiring an additional MBF scan for assessing mismatch areas between MBF and SNS.

  14. Dopamine D2 receptor radiotracers [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, Patrick N. [Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada)], E-mail: patrick.mccormick@camhpet.ca; Kapur, Shitij [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); PET Center, Center for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Seeman, Philip [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); PET Center, Center for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada)

    2008-01-15

    Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [{sup 11}C](+)-PHNO ([{sup 11}C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [{sup 3}H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for {sup 11}C and {sup 3}H. The specific binding ratio {l_brace}SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum){r_brace} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs responded indistinguishably in terms of both ED{sub 50} and Hill slope (e.g., (-)-NPA ED{sub 50} values are 0.027 and 0.023 mg/kg for [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride, respectively). In response to AMPH challenge, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [{sup 11}C](+)-PHNO- and [{sup 3}H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo

  15. 2-Aminobenzoic acid–4-(pyridin-4-yldisulfanyl)pyridine (1/1)

    OpenAIRE

    Hadi D. Arman; Trupta Kaulgud; Edward R. T. Tiekink

    2011-01-01

    The title 1:1 co-crystal, C7H7NO2·C10H8N2S2, features a highly twisted 4-(pyridin-4-yldisulfanyl)pyridine molecule [dihedral angle between the pyridine rings = 89.06 (10)°]. A small twist is evident in the 2-aminobenzoic acid molecule, with the C—C—C—O torsion angle being −7.7 (3)°. An N—H...O hydrogen bond occurs in the 2-aminobenzoic acid molecule. In the crystal, molecules are linked by O&#...

  16. Measurement of brain pH using 11CO2 and positron emission tomography

    International Nuclear Information System (INIS)

    Buxton, R.B.; Wechsler, L.R.; Alpert, N.M.; Ackerman, R.H.; Elmaleh, D.R.; Correia, J.A.

    1984-01-01

    We have examined the feasibility of measuring local brain pH in vivo with 11 CO 2 and positron emission tomography. In particular, we have addressed two objections that have been raised against this method: the assumed need to estimate local tissue PCO 2 and the rapid fixation of 11 C in tissue. From a reexamination of the basic theory, we argue that after administration of 11 CO 2 the time-dependent distribution of 11 C between tissue and blood is independent of the distribution of CO 2 already in the body, making it unnecessary to estimate local tissue PCO 2 . Assuming that the blood--brain barrier is impermeable to bicarbonate ions, there will be equal partial pressures of 11 CO 2 in blood and tissue at equilibrium. To overcome the problem of fixation in the tissue we have developed a kinetic model of the time-dependent distribution of 11 C that accounts for regional variations in blood flow, CO 2 extraction, pH, and rate of fixation. The values of the model parameters can be estimated from sequential measurements of tissue activity concentration during administration of 11 CO 2 . Tissue pH can then be calculated from one of the parameter values, a measurement of arterial pH, and known constants. Numerical calculations based on the kinetic model with assumed values of the parameters were used to optimize the experimental design. The calculations show that problems with fixation are much less severe with continuous infusion of activity than with bolus administration. During infusion the tissue curve depends strongly on tissue pH but only weakly on the rate of fixation

  17. Synthesis of [(11)C]Am80 via Novel Pd(0)-Mediated Rapid [(11)C]Carbonylation Using Arylboronate and [(11)C]Carbon Monoxide.

    Science.gov (United States)

    Takashima-Hirano, Misato; Ishii, Hideki; Suzuki, Masaaki

    2012-10-11

    (11)C-labeled methylbenzoates [(11)C]4a-d were synthesized using Pd(0)-mediated rapid cross-coupling reactions employing [(11)C]carbon monoxide and arylboronic acid neopentyl glycol esters 3a-d under atmospheric pressure in methanol-dimethylformamide (MeOH-DMF), in radiochemical yields of 12 ± 5-26 ± 13% (decay-corrected based on [(11)C]O). The reaction conditions were highly favorable for the synthesis of [(11)C]Am80 ([(11)C]2) and [(11)C]methyl 4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl)benzoate ([(11)C]2-Me) using 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)benzamide (5), both of which produced a decay-corrected radiochemical yield (RCY) of 26 ± 13%, with >99% radiochemical purity and an average specific radioactivity of 44 GBq/μmol. The yields of [(11)C]4a, [(11)C]2-Me, and [(11)C]2 were improved by the use of a 2-fold excess of the solvents and reagents under the same conditions to give respective yields of 66 ± 8, 65 ± 7, and 48 ± 2%.

  18. 2-Aminopyrimidine-3,3,3-triphenylpropanoic acid (1/1).

    Science.gov (United States)

    Serafin, Mateusz F; Wheeler, Kraig A

    2007-11-01

    The title bimolecular compound, C(4)H(5)N(3).C(21)H(18)O(2), constructed from 2-aminopyrimidine and 3,3,3-triphenylpropanoic acid, forms a tetramolecular hydrogen-bonded motif via O-H...N, N-H...O and N-H...N contacts. This aggregate organizes to give crystal-packing motifs with hydrophilic and hydrophobic regions.

  19. Evaluation of (+)-p-[11C]methylvesamicol for mapping sigma1 receptors: a comparison with [11C]SA4503

    International Nuclear Information System (INIS)

    Ishiwata, Kiichi; Kawamura, Kazunori; Yajima, Kazuyoshi; QingGeLeTu; Mori, Hirofumi; Shiba, Kazuhiro

    2006-01-01

    Vesamicol is a leading compound for positron emission tomography (PET) and single photon emission computed tomography (SPECT) tracers for mapping the vesicular acetylcholine transporter (VAChT). Recently, we found that (+)-p-methylvesamicol ((+)-PMV) has low affinity for VAChT (K i =199 nM), but has moderate to high affinity for sigma receptors: K i =3.0 nM for sigma 1 and K i =40.7 nM for sigma 2 , and that sigma 1 -selective SA4503 (K i =4.4 nM for sigma 1 and K i =242 nM for sigma 2 ) has moderate affinity for VAChT (K i =50.2 nM). In the present study, we examined the potential of (+)-[ 11 C]PMV as a PET radioligand for mapping sigma 1 receptors as compared with [ 11 C]SA4503. In rat brain, similar regional distribution patterns of (+)-[ 11 C]PMV and [ 11 C]SA4503 were shown by tissue dissection and by ex vivo autoradiography. Blocking experiments using (±)-PMV (-)-vesamicol, SA4503, haloperidol and (±)-pentazocine showed that the two tracers specifically bound to sigma 1 receptors, and that [ 11 C]SA4503 exhibited greater specific binding than (+)-[ 11 C]PMV. No sign of VAChT-specific binding by [ 11 C]SA4503 was observed in the striatum, which is rich in VAChT sites. In conclusion, (+)-[ 11 C]PMV specifically bound to sigma 1 receptors in the brain, but to a lesser extent than [ 11 C]SA4503, suggesting that (+)-[ 11 C]PMV is a less preferable PET ligand than [ 11 C]SA4503. On the other hand, the moderate affinity of [ 11 C]SA4503 for VAChT is negligible in vivo

  20. Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-{sup 11}C-propyl]n-propylnorapomorphine

    Energy Technology Data Exchange (ETDEWEB)

    Palner, Mikael [Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, DK-2300, Copenhagen (Denmark); Center for Integrated Molecular Brain Imaging, Copenhagen (Denmark)], E-mail: mikael.palner@nru.dk; McCormick, Patrick [PET Centre, Centre for Addiction and Mental Health, M5T 1RB, Toronto, ON (Canada); Gillings, Nic [Center for Integrated Molecular Brain Imaging, Copenhagen (Denmark); PET and Cyclotron Unit, Rigshospitalet, DK-2300, Copenhagen (Denmark); Begtrup, Mikael [Center for Integrated Molecular Brain Imaging, Copenhagen (Denmark); Institute for Medicinal Chemistry, Pharmaceutical Faculty, University of Copenhagen, DK-2300, Copenhagen (Denmark); Wilson, Alan A. [PET Centre, Centre for Addiction and Mental Health, M5T 1RB, Toronto, ON (Canada); Knudsen, Gitte M. [Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, DK-2300, Copenhagen (Denmark); Center for Integrated Molecular Brain Imaging, Copenhagen (Denmark)

    2010-01-15

    Introduction: Several dopamine D{sub 2} agonist radioligands have been used with positron emission tomography (PET), including [{sup 11}C-]-(-)-MNPA, [{sup 11}C-]-(-)-NPA and [{sup 11}C]-(+)-PHNO. These radioligands are considered particularly powerful for detection of endogenous dopamine release, but they either provide PET brain images with limited contrast or have affinity for both D{sub 2} and D{sub 3} receptors. We here present the carbon-11 radiolabeling and ex vivo evaluation of 2-Cl-(-)-NPA, a novel PET-tracer candidate with high in vitro D{sub 2}/D{sub 3} selectivity. Methods: 2-Cl-[{sup 11}C]-(-)-NPA and [{sup 11}C]-(-)-NPA were synthesized by a two step N-acylation-reduction process using [{sup 11}C]-propionyl chloride. Awake rats were injected with either tracer, via the tail vein. The rats were decapitated at various times, the brains were removed and quickly dissected, and plasma metabolites were measured. Radioligand specificity, and P-glycoprotein involvement in brain uptake, was also assessed. Results: 2-Cl-[{sup 11}C]-(-)-NPA and [{sup 11}C]-(-)-NPA were produced in high specific activity and purity. 2-Cl-[{sup 11}C]-(-)-NPA accumulated slower in the striatum than [{sup 11}C]-(-)-NPA, reaching maximum concentrations after 30 min. The maximal striatal uptake of 2-Cl-[{sup 11}C]-(-)-NPA (standard uptake value 0.72{+-}0.24) was approximately half that of [{sup 11}C]-(-)-NPA (standard uptake value 1.37{+-}0.18). Nonspecific uptake was similar for the two compounds. 2-Cl-[{sup 11}C]-(-)-NPA was metabolized quickly, leaving only 17% of the parent compound in the plasma after 30 min. The specific binding of 2-Cl-[{sup 11}C]-(-)-NPA was completely blocked and inhibition of P-glycoprotein did not alter the brain uptake. Conclusion: Ex vivo experiments showed, despite a favorable D{sub 2}/D{sub 3} selectivity, that 2-Cl-[{sup 11}C]-(-)-NPA is inferior to [{sup 11}C]-(-)-NPA as a PET tracer in rat, because of slower brain uptake and lower specific to

  1. Low-temperature heat capacities and standard molar enthalpy of formation of 4-(2-aminoethyl)-phenol(C8H11NO)

    Institute of Scientific and Technical Information of China (English)

    Di You-Ying; Kong Yu-Xia; Yang Wei-Wei; Tan Zhi-Cheng

    2008-01-01

    This paper reports that low-temperature heat capacities of 4-(2-aminoethyl)-phenol(C8H11NO)are measured by a precision automated adiabatic calorimeter over the temperature range from 78 to 400 K.A polynomial equation of heat capacities as a function of the temperature was fitted by the least square method.Based on the fitted polynomial,the smoothed heat capacities and thermodynamic functions of the compound relative to the standard reference temperature 298.15 K were calculated and tabulated at the interval of 5 K.The energy equivalent,gcalor,of the oxygen-bomb The constant-volume energy of combustion of the compound at T=298.15 K was measured by a precision oxygen-bomb combustion and other thermodynamic principles.Finally,the standard molar enthalpy of formation of the compound

  2. Cocrystals of the antimalarial drug 11-azaartemisinin with three alkenoic acids of 1:1 or 2:1 stoichiometry.

    Science.gov (United States)

    Nisar, Madiha; Wong, Lawrence W Y; Sung, Herman H Y; Haynes, Richard K; Williams, Ian D

    2018-06-01

    The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0 4,13 .0 8,13 ]hexadecan-10-one) with trans-cinnamic (Cin), maleic (Mal) and fumaric (Fum) acids are herein reported. trans-Cinnamic acid, a mono acid, forms 1:1 cocrystal 11-Aza:Cin (1, C 15 H 23 NO 4 ·C 9 H 8 O 2 ). Maleic acid forms both 1:1 cocrystal 11-Aza:Mal (2, C 15 H 23 NO 4 ·C 4 H 4 O 4 ), in which one COOH group is involved in self-catenation, and 2:1 cocrystal 11-Aza 2 :Mal (3, 2C 15 H 23 NO 4 ·C 4 H 4 O 4 ). Its isomer, fumaric acid, only affords 2:1 cocrystal 11-Aza 2 :Fum (4). All cocrystal formation appears driven by acid-lactam R 2 2 (8) heterosynthons with short O-H...O=C hydrogen bonds [O...O = 2.56 (2) Å], augmented by weaker C=O...H-N contacts. Despite a better packing efficiency, cocrystal 3 is metastable with respect to 2, probably due to a higher conformational energy for the maleic acid molecule in its structure. In each case, the microcrystalline powders from LAG were useful in providing seeding for the single-crystal growth.

  3. (2S-1,1-Dichloro-2-(2-chlorophenyl-2-(4-chlorophenylethane

    Directory of Open Access Journals (Sweden)

    Lars Eriksson

    2009-02-01

    Full Text Available The title compound, C14H10Cl4, is easily crystallized while the other enantiomorph only forms an oil upon crystallization attempts. The title compound has a considerably higher density, ρ ≃ 1.562 Mg m−3 compared to the racemic substance, ρ ≃ 1.514 Mg m−3. This is supported by the fact there are two intermolecular halogen–halogen contacts in the title compound compared with only one the racemic compound. The dihedral angle between the two phenyl rings is 76.83 (5°

  4. Preparation of no-carrier-added [1-11C]ethylene and [1-11C]1,2-dibromoethane as new labelling agents

    International Nuclear Information System (INIS)

    Shah, F.; Pike, V.W.; Dowsett, K.

    1997-01-01

    A method is described for the preparation of NCA [1- 11 C] ethylene based on the passage of [1- 11 C]ethanol over heated (550 o C) quartz glass in a stainless steel tube (in preference to dehydration by catalysis on γ-alumina or pyrolysis). The [1- 11 C]ethanol is prepared from cyclotron-produced NCA [ 11 C]carbon dioxide by 11 C-carboxylation of methylmagnesium bromide, freshly prepared in dibutyl ether, and reduction of the adduct with lithium aluminium hydride in diglyme. The use of involatile solvents avoids the formation of carrier ethylene and radioactive and stable diethyl ether by cracking processes over the heated catalyst. The preparation takes 21 min from the end of radionuclide production and has a radiochemical yield of 44%, decay-corrected from [ 11 C]carbon dioxide. NCA [1- 11 C] ethylene is converted quantitatively into [1- 11 C]1,2-dibromoethane when collected in a solution of bromine in carbon tetrachloride. The NCA [1- 11 C]ethylene and [1- 11 C]1,2-dibromoethane may serve as new and useful labelling agents. (Author)

  5. 4-((E-{2-[N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylcarboximidoyl]benzylidene}amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one

    Directory of Open Access Journals (Sweden)

    Richard Betz

    2011-10-01

    Full Text Available The title compound, C30H28N6O2, is a symmetric diimine derived from ortho-dibenzaldehyde. Both C=N bonds are (E-configured. The terminal N-bonded phenyl groups adopt staggered conformations relative to their respective parent heterocycles, the relevant least-squares planes intersect at angles of 32.35 (11 and 38.59 (10°. In the crystal, C—H...O contacts connect the molecules into chains along the b axis and give rise to a C11(14C11(14 and a R22(12 pattern on different levels of graph-set analysis. The shortest intercentroid distance between two centroids was found at 4.2074 (11 Å between the two five-membered heterocycles.

  6. NCI calculations for understanding a physical phase transition in (C6H14N2)[Mn(H2O)6](SeO4)2

    Science.gov (United States)

    Naïli, Houcine; François, Michel; Norquist, Alexander J.; Rekik, Walid

    2017-12-01

    An organically templated manganese selenate, (C6H14N2)[Mn(H2O)6](SeO4)2, has been synthesized by slow evaporation and crystallographically characterized. The title compound crystallizes at room temperature in the monoclinic centrosymmetric space group P21/n, with the following unit cell parameters: a = 7.2373(4) Å; b = 12.5600(7) Å; c = 10.1945(7) Å; β = 91.155(4)°, V = 926.50(10) Å3and Z = 2. Its crystal structure is built of manganese(II) cations coordinated by six water molecules in octahedral geometry, disordered dabcodiium cations and selenate anions, resulting in an extensive hydrogen-bonding network. Differential scanning calorimetry (DSC) measurement indicated that the precursor undergoes a reversible phase transition at about 216 and 218 K during the cooling and heating processes respectively. Below this temperature the title compound is noncentrosymmetric with space group P21 and lattice parameters a = 7.2033(8) Å; b = 12.4981(13) Å; c = 10.0888(11) Å; β = 91.281(2)°, V = 908.04(17) Å3 and Z = 2. The disorder-order transformation of the C atoms of (C6H14N2)2+ cation may drive the structural phase transition. The low temperature phase obtained by breaking symmetry presents a fully ordered structure. The noncovalent interaction (NCI) method was used not only to locate, quantify, and visualize intermolecular interactions in the high and low temperature phases but also to confirm the phase transition detected by DSC measurement. The thermal decomposition of this new compound proceeds through four stages giving rise to the manganese oxide as final product at 850 °C.

  7. Rapid solid-phase extraction method to quantify [{sup 11}C]-verapamil, and its [{sup 11}C]-metabolites, in human and macaque plasma

    Energy Technology Data Exchange (ETDEWEB)

    Unadkat, Jashvant D. [Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195 (United States)], E-mail: jash@u.washington.edu; Chung, Francisco; Sasongko, Lucy; Whittington, Dale; Eyal, Sara [Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195 (United States); Mankoff, David [Department of Radiology, University of Washington, Box 356004, Seattle, WA 98195 (United States); Collier, Ann C. [Department of Medicine, University of Washington, Box 359929, Seattle, WA 98195 (United States); Muzi, Mark; Link, Jeanne [Department of Radiology, University of Washington, Box 356004, Seattle, WA 98195 (United States)

    2008-11-15

    Introduction: P-glycoprotein (P-gp), an efflux transporter, is a significant barrier to drug entry into the brain and the fetus. The positron emission tomography (PET) ligand, [{sup 11}C]-verapamil, has been used to measure in vivo P-gp activity at various tissue-blood barriers of humans and animals. Since verapamil is extensively metabolized in vivo, it is important to quantify the extent of verapamil metabolism in order to interpret such P-gp activity. Therefore, we developed a rapid solid-phase extraction (SPE) method to separate, and then quantify, verapamil and its radiolabeled metabolites in plasma. Methods: Using high-performance liquid chromatography (HPLC), we established that the major identifiable circulating radioactive metabolite of [{sup 11}C]-verapamil in plasma of humans and the nonhuman primate, Macaca nemestrina, was [{sup 11}C]-D-617/717. Using sequential and differential pH elution on C{sub 8} SPE cartridges, we developed a rapid method to separate [{sup 11}C]-verapamil and [{sup 11}C]-D-617/717. Recovery was measured by spiking the samples with the corresponding nonradioactive compounds and assaying these compounds by HPLC. Results: Verapamil and D-617/717 recovery with the SPE method was >85%. When the method was applied to PET studies in humans and nonhuman primates, significant plasma concentration of D-617/717 and unknown polar metabolite(s) were observed. The SPE and the HPLC methods were not significantly different in the quantification of verapamil and D-617/717. Conclusions: The SPE method simultaneously processes multiple samples in less than 5 min. Given the short half-life of [{sup 11}C], this method provides a valuable tool to rapidly determine the concentration of [{sup 11}C]-verapamil and its [{sup 11}C]-metabolites in human and nonhuman primate plasma.

  8. Crystal structure of (1R,3S,8R,11R-11-acetyl-3,7,7-trimethyl-10-oxatricyclo[6.4.0.01,3]dodecan-9-one

    Directory of Open Access Journals (Sweden)

    Abdoullah Bismoussa

    2015-12-01

    Full Text Available The title compound, C16H24O3, is built up from three fused rings, a six-membered, a seven-membered and a three-membered ring. The absolute configuration of the title compound was determined as (1R,3S,8R,11R based on the synthetic pathway. The six-membered ring has an half-chair conformation whereas the seven-membered ring displays a boat conformation. In the cyrstal, C—H...O hydrogen bonds build up a two-dimensional network parallel to (0 0 1. The crystal studied was an inversion twin with a minor twin component of 34%.

  9. Dibromido[1,1′-dibutyl-2,2′-(pentane-1,1-diyldi-1H-benzimidazole]copper(II

    Directory of Open Access Journals (Sweden)

    Robert T. Stibrany

    2010-07-01

    Full Text Available In the title compound, [CuBr2(C27H36N4], the CuII ion exhibits a distorted tetrahedral coordination geometry provided by two bromide ions and by chelation of two imine N-atom donors from a bis(benzimidazole ligand. Chelation results in a six-membered boat-shaped ring which links the benzimidazole groups. Each bis(benzimidazole fragment contains three n-butyl substituents, two of which have the expected trans conformation; the third exhibits the higher-energy cis conformation, an orientation consistent with several short intramolecular C—H...Br interactions. Essentially planar (r.m.s. deviations of 0.0101 and 0.0183 Å benzimidazole groups are oriented so as to give the bis(benzimidazole fragment a V-shaped appearance in profile with the cis and trans n-butyl groups directed to opposite sides of the planes. In the crystal, columns of molecules along the b-axis direction form layers parallel to the (202 planes. Within a given column, the molecules are linked by C—H...Br hydrogen bonds. The molecules in adjacent columns are also linked by intermolecular C—H...π interactions, forming a three-dimensional network.

  10. Synthesis, single-crystal structure determination and Raman spectra of the tricyanomelaminates NaA{sub 5}[C{sub 6}N{sub 9}]{sub 2} . 4 H{sub 2}O (A = Rb, Cs)

    Energy Technology Data Exchange (ETDEWEB)

    Reckeweg, Olaf; DiSalvo, Francis J. [Cornell Univ., Ithaca, NY (United States). Baker Lab.; Schulz, Armin [Max-Planck-Institut fuer Festkoerperforschung, Stuttgart (Germany)

    2016-07-01

    Transparent colorless crystals of NaA{sub 5}[C{sub 6}N{sub 9}]{sub 2} . 4 H{sub 2}O (A = Rb, Cs) were obtained by blending aqueous solutions of Na{sub 3}[C{sub 6}N{sub 9}] and RbF or CsF, respectively, and subsequent evaporation of the water under ambient conditions. Both compounds crystallize in the space group P2{sub 1}/m (no. 11) with the cell parameters a = 815.56(16), b = 1637.7(4) and c = 1036.4(3) pm, and β = 110.738(12) for NaRb{sub 5}[C{sub 6}N{sub 9}]{sub 2} . 4 H{sub 2}O and a = 843.32(6), b = 1708.47(11) and c = 1052.42(7) pm, and β = 112.034(2) for NaCs{sub 5}[C{sub 6}N{sub 9}]{sub 2} . 4 H{sub 2}O, respectively. Raman spectra of the title compounds complement our results.

  11. A PET imaging agent with fast kinetics: synthesis and in vivo evaluation of the serotonin transporter ligand [{sup 11}C]2-[2-dimethylaminomethylphenylthio]-5-fluorophenylamine ([{sup 11}C]AFA)

    Energy Technology Data Exchange (ETDEWEB)

    Huang Yiyun E-mail: hh285@columbia.edu; Narendran, Raj; Bae, Sung-A; Erritzoe, David; Guo Ningning; Zhu Zhihong; Hwang, D.-R.; Laruelle, Marc

    2004-08-01

    A new serotonin transporter (SERT) ligand, [{sup 11}C]2-[2-(dimethylaminomethylphenylthio)]-5-fluorophenylamine (10, [{sup 11}C]AFA), was synthesized and evaluated as a candidate PET radioligand in pharmacological and pharmacokinetic studies. As a PET radioligand, AFA (8) can be labeled with either C-11 or F-18. In vitro, AFA displayed high affinity for SERT (K{sub i} 1.46{+-}0.15 nM) and lower affinity for norepinephrine transporter (NET, K{sub i} 141.7{+-}47.4 nM) or dopamine transporter (DAT, K{sub i} >10,000 nM). [{sup 11}C]AFA (10) was prepared from its monomethylamino precursor 9 by reaction with high specific activity [{sup 11}C]methyl iodide. Radiochemical yield was 43{+-}20% based on [{sup 11}C]methyl iodide at end of bombardment (EOB, n = 10) and specific activity was 2,129 {+-} 1,369 Ci/mmol at end of synthesis (EOS, n = 10). Biodistribution studies in rats indicated that [{sup 11}C]AFA accumulated in brain regions known to contain high concentrations of SERT. Binding in SERT-rich brain regions was reduced significantly by pretreatment with either the cold compound 8 or with the selective serotonin reuptake inhibitor (SSRI) citalopram, but not by the selective norepinephrine reuptake inhibitor nisoxetine, thus underlining its in vivo binding selectivity and specificity for SERT. Imaging experiments in baboons demonstrated that the uptake pattern of [{sup 11}C]AFA in the baboon brain is consistent with the known distribution of SERT, with highest activity levels in the midbrain and thalamus, followed by striatum, hippocampus, and cortical regions. Activity levels in the baboon brain peaked at 15-40 min after radioligand injection, indicating a fast uptake kinetics for [{sup 11}C]AFA. Pretreatment of the baboon with citalopram (4 mg/kg) significantly reduced the specific binding of [{sup 11}C]AFA in all SERT-containing brain regions. Kinetic analysis revealed that the regional equilibrium specific to non-specific partition coefficients (V{sub 3}&apos

  12. Methyl 5,7-dihydroxy-2,2,9-trimethyl-6,11-dioxo-6,11-dihydro-2H-anthra[2,3-b]pyran-8-carboxylate

    Directory of Open Access Journals (Sweden)

    Annelise Lobstein

    2008-12-01

    Full Text Available The title compound, C22H18O7, also known as laurentiquinone B, is a new anthraquinone which was isolated from Vismia laurentii, a Cameroonian medicinal plant. The asymmetric unit contains two independent molecules. Each of them contains four fused rings, three of which are coplanar and typical of anthracene, while the heterocyclic rings adopt envelope conformations. Intramolecular O—H...O hydrogen bonds result in the formation of two planar rings, which are also almost coplanar with the adjacent rings. In the crystal structure, intermolecular O—H...O and C—H...O hydrogen bonds link the molecules and a π–π contact is also present [centroid-centroid distance = 3.967 (3 Å].

  13. A study of 11C-acetate production using 11C-choline commercial module

    International Nuclear Information System (INIS)

    Zhang Jinming; Tian Jiahe; Yao Shulin; Chen Yan

    2008-01-01

    Objective: 11 C-acetate is a useful PET tracer in evaluating myocardial metabolism but more interest has been focused on its application in tumor detection in recent years, especially hepatocellular carcinoma (HCC). This study was designed to evaluate the laboratory, preparation of 11 C-acetate with a modified 11 C-choline commercial module and to investigate its biodistribution in tumor (lung adenocarcinoma)-bearing mice as well as its potential as a tumor imaging agent. Methods: 11 C-acetate was synthesized with a modified 11 C choline module: Methyl magnesium bromide Grignard (0.1 ml of 1.5 mol/L) was load- ed to a Teflon loop before 11 CO 2 was recovered from the target. Cartier acetate solution (2 ml of 1 mmol/L) was pushed through the loop, SPE cartridges (mixed AG50 and IC-Ag) and then the QMA. The loop and cartridges were then rinsed with water. The product 11 C-acetate was then washed out from QMA with 0.9% NaCl solution into a collection vial containing diluted HCl. 11 C-carbonate was removed by nitrogen bubbling for 2 min. After neutralization with trisodium citrate, the injectable 11 C-acetate solution was obtained. The tumor-bearing mice were sacrificed. The percentage activity of injected dose per gram of tissue (% ID/g) for tumor and other tissues were calculated. One patient with known diagnosis of moderately differentiated HCC was injected with 11 C-acetate and imaged by PET/CT, followed by 18 F-fluorodeoxyglucose (FDG). Results: The synthesis yield of 11 C-acetate was (60.5 ± 8.7)% (decay conected, n=10); the radio-chemistry purity was > 98% and the synthesis time was 10 min from 11 CO 2 to 11 C-acetate. The radioactivity ratio for tumor/muscle was 1.76 at 30 min. A patient with known HCC showed positive 11 C-acetate accumulation in the tumor but was negative in 18 F-FDG. Conclusion: The synthesis of 11 C-acetate by modification of an 11 C-choline commercial module was feasible and it could be achieved with high yield, high radiochemical purity

  14. Simplified PET measurement for evaluating histamine H1 receptors in human brains using [11C]doxepin

    International Nuclear Information System (INIS)

    Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Oda, Keiichi; Sasaki, Toru; Tashiro, Manabu; Yanai, Kazuhiko; Ishiwata, Kiichi

    2004-01-01

    The aim of this study was to develop simplified positron emission tomography measurement using [ 11 C]doxepin ([ 11 C]DOX) to evaluate histamine H 1 receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [ 11 C]DOX, estimated quantitatively with a two-compartment model, and the [ 11 C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [ 11 C]DOX-H1R binding

  15. 2-(4-Fluorophenyl-2H-chromen-4(3H-one

    Directory of Open Access Journals (Sweden)

    Michał Wera

    2012-02-01

    Full Text Available In the crystal structure of the title compound, C15H11FO2, molecules form inversion dimers through pairs of weak C—H...O hydrogen bonds. Dimers oriented in parallel, linked by C—H...π contacts, are arranged in columns along the b axis. The fluorophenyl ring and the benzene ring of the 2H-chromen-4(3H-one unit are inclined to one another by 70.41 (16°. They are respectively parallel in a given column or almost perpendicular [oriented at an angle of 87.8 (1°] in neighbouring (inversely oriented columns, forming a herringbone pattern.

  16. 2-(4-Methoxy-1H-indol-3-ylacetonitrile

    Directory of Open Access Journals (Sweden)

    Yong-Hong Lu

    2012-01-01

    Full Text Available In the title compound, C11H10N2O, the cyanide group is twisted away from the indole-ring plane [Ccy—Cme—Car—Car = 70.7 (2°; cy = cyanide, me = methylene, ar = aromatic], whereas the methoxy C atom is almost coplanar with the ring system [displacement = 0.014 (5 Å]. In the crystal, N—H...N hydrogen bonds link the molecules into C(7 chains propagating in [100].

  17. Automatic synthesis of [11C]NKY-722 with high specific activity, using anhydrous [11C] methanol as a precursor

    International Nuclear Information System (INIS)

    Suzuki, Kazutoshi; Inoue, Osamu; Itoh, Takashi; Nemoto, Kazuyoshi; Oosumi, Seimei; Miwa, Soichi.

    1992-01-01

    3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl- 4-(3-nitrophenyl)-3,5-pyridine dicarboxylate (NKY-722) was labeled with carbon-11 using anhydrous [ 11 C] methanol. Using a computer controlled equipment, a few GBq of [ 11 C] NKY-722 with the specific activity of 120 - 180 GBq/μmol could by synthesized at the radiochemical purity of > 99% in 10 ml of physiological saline containing Polysolvate-80 (1.5 vol%) and ethyl alcohol (0.75 vol%). Preliminary PET experiments using rats and a rhesus monkey have bee done, and very low accumulation of the compound into the brain, however comparatively higher accumulation in the heart were observed. (author)

  18. A facile route towards the synthesis of 2-(1H-indol-3-yl)-acetamides using 1,1-carbonyldiimidazole

    International Nuclear Information System (INIS)

    Kanwal, F.; Khan, K.M.; Fatima, B.; Bano, B.; Salar, U.

    2016-01-01

    A base-catalyzed one pot reaction has been developed for the synthesis of 2-(1H-indol-3-yl)-acetamides via coupling of 1,1-carbonyldiimidazole with 2-(1H-indol-3-yl) acetic acid resulting in the formation of a reactive intermediate which on treatment with different substituted anilines afford 2-(1H-indol-3-yl)-acetamides in good yield. The use of base along with coupling reagent eases the formation of intermediate in minimum time. All the synthetic compounds were obtained in good to moderate yields, the use of various substituted anilines effects the yields of the products. Compounds 4-30 were synthesized and the structures of all the synthetic compounds were determined by using spectroscopic techniques such as 1H-, 13C-NMR, EIMS and HRMS. (author)

  19. 2-Aminobenzoic acid–4-(pyridin-4-yldisulfanylpyridine (1/1

    Directory of Open Access Journals (Sweden)

    Hadi D. Arman

    2011-12-01

    Full Text Available The title 1:1 co-crystal, C7H7NO2·C10H8N2S2, features a highly twisted 4-(pyridin-4-yldisulfanylpyridine molecule [dihedral angle between the pyridine rings = 89.06 (10°]. A small twist is evident in the 2-aminobenzoic acid molecule, with the C—C—C—O torsion angle being −7.7 (3°. An N—H...O hydrogen bond occurs in the 2-aminobenzoic acid molecule. In the crystal, molecules are linked by O—H...N and N—H...N hydrogen bonds into a supramolecular chain along the b axis. These are connected into layers by π–π interactions occurring between pyridine rings [centroid–centroid distance = 3.8489 (15 Å]. The layers are connected along the a axis by C—H...O contacts. The crystal studied was a racemic twin.

  20. Radiosynthesis of [11C]D.P.A.-713, [11C]D.P.A.-715 and [11C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    International Nuclear Information System (INIS)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B.; Kassiou, M.; James, M.; Creelman, A.; Fulton, R.; Kassiou, M.; Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C.; Selleri, S.

    2008-01-01

    11 C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon 11 (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[ 11 C]methyl iodide (in D.M.S.O./D.M.F (100/200 μL) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [ 11 C]methyl triflate (in acetone (300μL) containing aq. 3 M NaOH (4μL) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  1. Synthesis of [11C]cyanoalkyltriphenylphosphoranes via [11C]cyanide substitution on haloalkylphosphonium salts

    International Nuclear Information System (INIS)

    Hoernfeldt, K.

    1994-01-01

    The synthesis of the 11 C-labelled bifunctional precursors 3-[ 11 C]cyanoethyltriphenylphosphonium bromide (1'), 4-[ 11 C]cyanopropyltriphenylphosphonium bromide (2'), 5-[ 11 C]cyanobutyltriphenylphosphonium bromide (3'), 4-[ 11 C]cyanopropyltriphenylphosphonium iodide (4') and 5-[ 11 C]cyanobutyltriphenylphosphonium iodide (5') is presented. The label was introduced using [ 11 C]cyanide in a substitution reaction on the ω-halo-alkyltriphenylphosphonium salt (bromide or iodide salt). The phosphonium salts 1'-5' were formed in 33-99% radiochemical yield in 5-10 min reaction time. After addition of epichlorohydrin as generator of base, the precursors 1-3 were formed. The potential of the intermediates 1-3 in Wittig reactions was shown in model reactions with aromatic and aliphatic aldehydes. The aromatic olefins obtained from 1'-5' were formed in 85-96% radiochemical yield, with Z/E ratios between 67/33-75/25. The aliphatic olefins were obtained in 60-78% radiochemical yield from 4' and 5'. In the reaction with 1' and an aliphatic aldehyde, the yield decreased to 5-10%. The Z/E ratios were 100/0 for the aliphatic olefins. In an experiment starting with 2,7 GBq (73 mCi) hydrogen [ 11 C]cyanide, 451 MBq (12.2 mCi) olefin from 3' and 4-nitrobenzaldehyde was obtained in 44 min from hydrogen [ 11 C]cyanide production, with a 55% decay corrected radiochemical yield, the radiochemical purity was 96%. (Author)

  2. Crystal structure, quantum mechanical investigation, IR and NMR spectroscopy of two new organic perchlorates: (C6H18N3)·(ClO4)3H2O (I) and (C9H11N2)·ClO4(II)

    Science.gov (United States)

    Bayar, I.; Khedhiri, L.; Soudani, S.; Lefebvre, F.; Ferretti, V.; Ben Nasr, C.

    2018-06-01

    The reaction of perchloric acid with 1-(2-aminoethyl)piperazine or 5,6-dimethyl-benzimidazole results in the formation of 1-(2-amonioethyl)piperazine-1,4-dium triperchlorate hydrate (C6H18N3)·(ClO4)3·H2O (I) or 5,6-dimethyl-benzylimidazolium perchlorate (C9H11N2)·ClO4(II). Both compounds were fully structurally characterized including single crystal X-ray diffraction analysis. Compound (I) crystallizes in the centrosymmetric triclinic space group P 1 bar with the lattice parameters a = 7.455 (2), b = 10.462 (2), c = 10.824 (2) Å, α = 80.832 (2), β = 88.243 (2), γ = 88.160 (2) °, Z = 2 and V = 832.77 (3) Å3. Compound (II) has been found to belong to the P21/c space group of the monoclinic system, with a = 7.590 (3), b = 9.266 (3), c = 16.503 (6) Å, β = 107.38 (2) °, V = 1107.69 (7) Å3 and Z = 4. The structures of (I) and (II) consist of slightly distorted [ClO4]- tetrahedra anions and 1-(2-amonioethyl)piperazine-1,4-dium trication (I) or 5,6-dimethyl-benzylimidazolium cations (II) and additionally a lattice water in (I). The crystal structures of (I) and (II) exhibit complex three-dimensional networks of H-bonds connecting all their components. In the atomic arrangement of (I), the ClO4- anions form corrugated chains, while in (II) the atomic arrangement exhibits wide pseudo-hexagonal channels of ClO4 tetrahedra including the organic entities. The lattice water serves as a link between pairs of cations and pairs of anions via several Osbnd H⋯O and N-H⋯O interactions in compound (I). The vibrational absorption bands were identified by infrared spectroscopy. These compounds were also investigated by solid-state 13C, 35Cl and 15N NMR spectroscopy. DFT calculations allowed the attribution of the IR and NMR bands. Intermolecular interactions were investigated by Hirshfeld surfaces. Electronic properties such as HOMO and LUMO energies were derived.

  3. Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand

    International Nuclear Information System (INIS)

    Airaksinen, Anu J.; Jablonowski, Jill A.; Mey, Margreet van der; Barbier, Ann J.; Klok, Rob P.; Verbeek, Joost; Schuit, Robert; Herscheid, Jacobus D.M.; Leysen, Josee E.; Carruthers, Nicholas I.; Lammertsma, Adriaan A.; Windhorst, Albert D.

    2006-01-01

    The potent histamine H 3 receptor antagonist JNJ-10181457 () was successfully labeled with 11 C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28±8%) and high specific radioactivity (56±26 GBq/μmol). The binding of [ 11 C] to H 3 receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [ 11 C] in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H 3 antagonists, JNJ-5207852 () and unlabeled Compound (), in a concentration-dependent manner. The biodistribution of [ 11 C] in rats was measured at 5, 10, 30 and 60 min. The uptake of [ 11 C] in regions rich in H 3 receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [ 11 C] in the rat brain could not be blocked by pretreatment with either Compound () (30 min or 24 h pretreatment) or cold Compound () (30-min pretreatment). The biodistribution of [ 11 C] in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H 3 (-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [ 11 C] could not specifically label H 3 receptors in rodent brain in vivo. Possible causes are discussed

  4. Evaluation of (+)-p-[{sup 11}C]methylvesamicol for mapping sigma{sub 1} receptors: a comparison with [{sup 11}C]SA4503

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0022 (Japan)]. E-mail: ishiwata@pet.tmig.or.jp; Kawamura, Kazunori [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0022 (Japan); SHI Accelerator Service Ltd., Tokyo 141-0032 (Japan); Yajima, Kazuyoshi [The Medical and Pharmacological Research Center Foundation, Hakui 920-0631 (Japan); QingGeLeTu [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0022 (Japan); Mori, Hirofumi [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Shiba, Kazuhiro [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan)

    2006-05-15

    Vesamicol is a leading compound for positron emission tomography (PET) and single photon emission computed tomography (SPECT) tracers for mapping the vesicular acetylcholine transporter (VAChT). Recently, we found that (+)-p-methylvesamicol ((+)-PMV) has low affinity for VAChT (K {sub i}=199 nM), but has moderate to high affinity for sigma receptors: K {sub i}=3.0 nM for sigma{sub 1} and K {sub i}=40.7 nM for sigma{sub 2}, and that sigma{sub 1}-selective SA4503 (K {sub i}=4.4 nM for sigma{sub 1} and K {sub i}=242 nM for sigma{sub 2}) has moderate affinity for VAChT (K {sub i}=50.2 nM). In the present study, we examined the potential of (+)-[{sup 11}C]PMV as a PET radioligand for mapping sigma{sub 1} receptors as compared with [{sup 11}C]SA4503. In rat brain, similar regional distribution patterns of (+)-[{sup 11}C]PMV and [{sup 11}C]SA4503 were shown by tissue dissection and by ex vivo autoradiography. Blocking experiments using ({+-})-PMV (-)-vesamicol, SA4503, haloperidol and ({+-})-pentazocine showed that the two tracers specifically bound to sigma{sub 1} receptors, and that [{sup 11}C]SA4503 exhibited greater specific binding than (+)-[{sup 11}C]PMV. No sign of VAChT-specific binding by [{sup 11}C]SA4503 was observed in the striatum, which is rich in VAChT sites. In conclusion, (+)-[{sup 11}C]PMV specifically bound to sigma{sub 1} receptors in the brain, but to a lesser extent than [{sup 11}C]SA4503, suggesting that (+)-[{sup 11}C]PMV is a less preferable PET ligand than [{sup 11}C]SA4503. On the other hand, the moderate affinity of [{sup 11}C]SA4503 for VAChT is negligible in vivo.

  5. Skeleton polyhedral rearrangements of 8-alkyl-7,9-dicarba-nido-undecaborate(-1) anion to 11-alkyl-2,7-dicarba-nido-undecaborane(13) and to 9-alkyl-7,8-dicarba-nido-undecaborate(-1) anion. Molecular structure of 2,7-Me2-11-PhCH2-2,7-C2B9H10

    International Nuclear Information System (INIS)

    Zakharkin, K.I.; Zhigareva, G.G.; Antonovich, V.A.; Yanovskij, A.I.; Struchkov, Yu.T.

    1986-01-01

    Using the methods of 1 H and 11 B NMR-spectroscopy and X-ray diffraction analysis skeleton polyhedral rearrangements of carboranes are studied. During protonation of anion 8-R-7, 9-R' 2 -7, 9-C 2 B 9 H 9 - the skeleton polyhedral rearrangement in the series of nido-carboranes, resulting in 2,7-R' 2 -11-R-2, 7-C 2 B 9 H 10 (R=Me, PhCH 2 , R'=H, Me) is observed. The rearrangement is reversible. On the detachment of two protons from 2,7-Me 2 -11-PhCH 2 -2,7-C 2 B 9 H 10 and during subsequent protonation the skeleton polyhedral rearrangement with the formation of anion 9-PhCH 2 -7,8-Me 2 -7,8-C 2 B 9 H 9 - takes place

  6. Crystal structure of fac-[2-(4-methyl-5-phenylpyridin-2-ylphenyl-κ2C1,N]bis[2-(pyridin-2-ylphenyl-κ2C1,N]iridium(III

    Directory of Open Access Journals (Sweden)

    Chi-Heon Lee

    2016-12-01

    Full Text Available In the title compound, [Ir(C11H8N2(C18H14N], the IrIII ion adopts a distorted octahedral coordination environment defined by three C,N-chelating ligands, one stemming from a 2-(4-phenyl-5-methylpyridin-2-ylphenyl ligand and two from 2-(pyridin-2-ylphenyl ligands, arranged in a facial manner. The IrIII ion lies almost in the equatorial plane [deviation = 0.0069 (15 Å]. In the crystal, intermolecular π–π stacking interactions, as well as intermolecular C—H...π interactions, are present, leading to a three-dimensional network.

  7. Tracers development for the PET study of nicotinic receptors: [11C]-mecamylamine and [11C]-SIB 1553A. Tritium and carbon-11 radiolabelling of a serine proteinase inhibitor: the t-PAstop

    International Nuclear Information System (INIS)

    Sobrio, F.

    2002-12-01

    In order to develop radiotracers for the Positron Emission Tomography (PET), we labelled both the mecamylamine and SIB-1553A with carbon-11 to study the nicotinic cholinergic receptors (nAChRs). The radiosynthesis of [ 11 C]-t-PA stop and the labelling with tritium of one analogue were realized for cerebral ischemia PET studies. The [ 11 C]-mecamylamine, a non-competitive and non-selective nAChRs antagonist was synthesized in 45 min via a N-[ 11 C]-methylation reaction. In the rat brain, the ex vivo studies showed no radio-metabolite 45 min after the injection of [ 11 C]-mecamylamine. The uptake kinetics in the rat brain or in vivo by PET in the anesthetized baboon or in the conscious monkey, reached a plateau around 45-50 min after injection. However, the saturation or displacement experiments did not permit to exhibit nor a significant difference of labelling between the different cerebral regions nor a specific uptake. In consequence, the [ 11 C]-mecamylamine was not an appropriate radioligand for nAChRs PET study. The labelling of [ 11 C]-SIB 1553A, a selective agonist for the nicotinic β4 subunit, required the synthesis in 5 steps (56% overall yield) of precursor for the incorporation of carbon-11. The radiosynthesis was performed in 36 min by a N-[ 11 C]-methylation reaction (yield: 75%). The [ 11 C]-t-PA stop was obtained from [ 11 C]-KCN with yields from 80 to 90%. For the first time with carbon-11, the formation of an amidine group was realized from a nitrile group. The labelling by isotopic exchange of hydrogen by tritium of the t-PA stop did not permit to obtain the [ 3 H]-t-PA stop but a tritiated analogue. This compound will be used to study its vectorization by micro-encapsulation. (author)

  8. Synthesis of [11C]-Sarin

    International Nuclear Information System (INIS)

    Prenant, C.; Crouzel, C.

    1990-01-01

    [ 11 C]-acetone, prepared from 11 CO 2 and methyllithium, was reduced to [ 11 C]-isopropanol. The latter reacted with methylphosphonic acid difluoride in the presence of diisopropylamine, to yield [11C]-sarin. 3.4 GBq (100 mCi) of [ 11 C]-sarin may be obtained from about 55.5 GBq (1.5 Ci) of 11 CO 2 in 40 minutes. The product purified by HPLC, is obtained with a specific radioactivity ranging from 22.2 to 33.3 GBq (600 to 900 mCi/μmol.). (author)

  9. (S-2-(2-Pyrrolidinio-1H-benzimidazol-3-ium dichloride monohydrate

    Directory of Open Access Journals (Sweden)

    Dai Jing

    2009-06-01

    Full Text Available In the title compound, C11H15N32+·2Cl−·H2O, one N atom of the imidazole ring and the N atom of the pyrrolidine ring are protonated. The crystal structure is stabilized by aromatic π–π interactions between the benzene rings of neighbouring benzimidazole systems [centroid–centroid duistance = 3.712 (2 Å]. The crystal structure is further stabilized by intermolecular N—H...Cl, O—H...Cl and N—H...O hydrogen bonds.

  10. Synthesis and preclinical evaluation of [11C-carbonyl]PF-04457845 for neuroimaging of fatty acid amide hydrolase

    International Nuclear Information System (INIS)

    Hicks, Justin W.; Parkes, Jun; Sadovski, Oleg; Tong, Junchao; Houle, Sylvain; Vasdev, Neil; Wilson, Alan A.

    2013-01-01

    Introduction: Fatty acid amide hydrolase (FAAH) has a significant role in regulating endocannabinoid signaling in the central nervous system. As such, FAAH inhibitors are being actively sought for pain, addiction, and other indications. This has led to the recent pursuit of positron emission tomography (PET) radiotracers targeting FAAH. We report herein the preparation and preclinical evaluation of [ 11 C-carbonyl]PF-04457845, an isotopologue of the potent irreversible FAAH inhibitor. Methods: PF-04457845 was radiolabeled at the carbonyl position via automated [ 11 C]CO 2 -fixation. Ex vivo brain biodistribution of [ 11 C-carbonyl]PF-04457845 was carried out in conscious rats. Specificity was determined by pre-administration of PF-04457845 or URB597 prior to [ 11 C-carbonyl]PF-04457845. In a separate experiment, rats injected with the title radiotracer had whole brains excised, homogenized and extracted to examine irreversible binding to brain parenchyma. Results: The title compound was prepared in 5 ± 1% (n = 4) isolated radiochemical yield based on starting [ 11 C]CO 2 (decay uncorrected) within 25 min from end-of-bombardment in > 98% radiochemical purity and a specific activity of 73.5 ± 8.2 GBq/μmol at end-of-synthesis. Uptake of [ 11 C-carbonyl]PF-04457845 into the rat brain was high (range of 1.2–4.4 SUV), heterogeneous, and in accordance with reported FAAH distribution. Saturable binding was demonstrated by a dose-dependent reduction in brain radioactivity uptake following pre-treatment with PF-04457845. Pre-treatment with the prototypical FAAH inhibitor, URB597, reduced the brain radiotracer uptake in all regions by 71–81%, demonstrating specificity for FAAH. The binding of [ 11 C-carbonyl]PF-04457845 to FAAH at 40 min post injection was irreversible as 98% of the radioactivity in the brain could not be extracted. Conclusions: [ 11 C-carbonyl]PF-04457845 was rapidly synthesized via an automated radiosynthesis. Ex vivo biodistribution studies in

  11. Synthesis and characteristics of a novel 3-D organic amine oxalate: (enH2)1.5[Bi3(C2O4)6(CO2CONHCH2CH2NH3)].6.5H2O

    International Nuclear Information System (INIS)

    Yu Xiaohong; Zhang Hanhui; Cao Yanning; Chen Yiping; Wang Zhen

    2006-01-01

    A novel 3-D compound of (enH 2 ) 1.5 [Bi 3 (C 2 O 4 ) 6 (CO 2 CONHCH 2 CH 2 NH 3 )].6.5H 2 O has been hydrothermally synthesized and characterized by IR, ultraviolet-visible diffuse reflection integral spectrum (UV-Vis DRIS), fluorescence spectra, TGA and single crystal X-ray diffraction. It crystallizes in the monoclinic system, space group C2/c with a=31.110(8)A, b=11.544(3)A, c=22.583(6)A, β=112.419(3) o , V=7497(3)A 3 , Z=8, R 1 =0.0463 and wR 2 =0.1393 for unique 7686 reflections I>2σ(I). In the title compound, the Bi atoms have eight-fold and nine-fold coordination with respect to the oxygen atoms, with the Bi atoms in distorted dodecahedron and monocapped square antiprism, respectively. The 3-D framework of the title compound contains channels and is composed of linkages between Bi atoms and oxalate units, forming honeycomb-like layers with two kinds of 6+6 membered aperture, and pillared by oxalate ligands and monamide groups. The channels have N-ethylamine oxalate monamide group - CO 2 CONHCH 2 CH 2 NH 3 + , which is formed by the in situ reaction of en and oxalate acid. At room temperature, the complex exhibits intense blue luminescence with an emission peak at 445nm

  12. Synthesis of dimethyl-1,1 guanylguanidine-{sup 14}C-2,4 (dimethyl-1-1 biguanide) hydrochloride; Synthese du chlorhydrate de dimethyl-1,1 guanylguanidine {sup 14}C-2,4 (dimethyl-1-1 biguanide)

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, M; Pichat, L [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1961-07-01

    A description of the synthesis of dimethyl-1,1 guanylguanidine-{sup 14}C-2,4 hydrochloride passing through the {sup 14}C{sub 2} dicyandiamide. The overall yield with respect to Ba{sup 14}CO{sub 3} is 38 per cent. (author) [French] Description de la synthese du chlorhydrate de dimethyl-1,1 guanylguanidine {sup 14}C-2,4 par l'intermediaire de la dicyandiamide {sup 14}C{sub 2}. Le rendement global par rapport a {sup 14}CO{sub 3}Ba est de 38 pour cent. (auteur)

  13. C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan [Hospital for Sick Children, Diagnostic Imaging, Toronto (Canada); Clarke, Howard [Hospital for Sick Children, Plastic Surgery, Toronto (Canada); Weksberg, Rosanna [Hospital for Sick Children, Clinical and Metabolic Genetics, Toronto (Canada)

    2008-07-15

    Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

  14. C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

    International Nuclear Information System (INIS)

    Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan; Clarke, Howard; Weksberg, Rosanna

    2008-01-01

    Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

  15. 2-Methyl-1,10b-dihydro-5H-pyrazolo[1,5-c][1,3]benzoxazin-5-one

    Directory of Open Access Journals (Sweden)

    Jan Světlík

    2009-05-01

    Full Text Available In the title compound, C11H10N2O2, a potential inhibitor of the cyclooxygenase-2 isoenzyme, the pyrazoline ring exists in a flat-envelope conformation while the puckering of the central oxazine ring is more severe. As a result, the molecule as a whole is non-planar. The formal sp3 pyrazoline N atom is sp2 hybridized, with the lone-pair electrons delocalized through conjugation with the carbonyl group rather than the double bond of the pyrazoline ring.

  16. 1-(1-Hydroxy-9H-carbazol-2-yl-3-methylbut-2-en-1-one

    Directory of Open Access Journals (Sweden)

    Matthias Zeller

    2010-02-01

    Full Text Available The title compound, C17H15NO2, was prepared as one of two products of the AlCl3/POCl3-catalysed reaction of 9-carbazol-1-ol with 3,3-dimethyacrylic acid. It crystallizes with two crystallographically independent molecules, A and B, which are virtually superimposable but not related by any translational or other pseudosymmetry. Both independent molecules are almost planar [r.m.s. deviations from planarity = 0.053 (1 and 0.079 (1 Å in A and B, respectively] and contain an intramolecular O—H...O hydrogen bond. Each type of molecules is connected via pairs of N—H...O hydrogen bonds, forming centrosymmetric A2 and B2 dimers which are, in turn, arranged in offset π-stacks extending along the a-axis direction. The offset of the dimers and the tilt angle of the molecules allows the formation of alternating C—H...π interactions between A and B molecules of parallel stacks.

  17. Crystal structure of {(R-N2-[(benzo[h]quinolin-2-ylmethyl]-N2′-[(benzo[h]quinolin-2-ylmethylidene]-1,1′-binaphthyl-2,2′-diamine-κ4N,N′,N′′,N′′′}(trifluoromethanesulfonato-κOzinc(II} trifluoromethanesulfonate dichloromethane 1.5-solvate

    Directory of Open Access Journals (Sweden)

    Shayna R. Skokan

    2017-07-01

    Full Text Available The zinc(II atom in the title compound, [Zn(C48H31N4(CF3SO3](CF3SO3·1.5CH2Cl2, adopts a distorted five-coordinate square-pyramidal geometry. It is coordinated by one trifluoromethanesulfonate ligand and four N atoms of the N2-[(benzo[h]quinolin-2-ylmethyl]-N2′-[(benzo[h]quinolin-2-ylmethylidene]-1,1′-binaphthyl-2,2′-diamine ligand. The complex is present as a single-stranded P-helimer monohelical structure incorporating π–π and/or σ–π interactions. One of the imine bonds present in the original ligand framework is reduced, leading to variations in bond lengths and torsion angles for each side of the ligand motif. The imine-bond reduction also affects the bond lengths involving the metal atom with the N-donor atoms located on the imine bond. There are two molecules of the complex in the asymmetric unit. One of the molecules exhibits positional disorder within the coordinating trifluoromethanesulfonate ion making the molecules symmetrically non-equivalent.

  18. On-line production of [11C]cyanogen bromide

    International Nuclear Information System (INIS)

    Westerberg, G.; Laangstroem, B.

    1997-01-01

    The electrophilic labelling precursor [ 11 C]cyanogen bromide was produced in 95% radiochemical yield (decay-corrected) from hydrogen [ 11 C]cyanide within 3 min from the end of bombardment using a simple and convenient solid-phase on-line procedure. The [ 11 C]cyanogen bromide has been used in the synthesis of a number of labelled compounds for use in positron emission tomography. (author)

  19. Comparative PET studies of the distribution of ( - )-3,4-methylenedioxy-N-[11C]methamphetamine and ( - )-[11C]methamphetamine in a monkey brain

    International Nuclear Information System (INIS)

    Shiue Chyngyann; Shiue, Grace G.; Cornish, Kurtis G.; O'Rourke, Maria F.

    1995-01-01

    Carbon-11 labeled ( - )-methamphetamine and ( - )-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [ 11 C]H 3 I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/μM. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of ( - )-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as ( - )-methamphetamine while only 3% remained as ( - )-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes

  20. Radiosynthesis of [{sup 11}C]D.P.A.-713, [{sup 11}C]D.P.A.-715 and [{sup 11}C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B. [Service Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); Kassiou, M.; James, M.; Creelman, A.; Fulton, R. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia); Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C. [Radiopharmaceuticals Research Institute, ANSTO, NSW (Australia); Selleri, S. [Degli Studi di Firenze Univ., Dipt. di Scienze Farmaceutiche (Italy)

    2008-02-15

    {sup 11}C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon{sup 11} (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[{sup 11}C]methyl iodide (in D.M.S.O./D.M.F (100/200 {mu}L) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [{sup 11}C]methyl triflate (in acetone (300{mu}L) containing aq. 3 M NaOH (4{mu}L) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  1. Optimizing an online SPE-HPLC method for analysis of (R)-[11C]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)- 3-isoquinolinecarboxamide [(R)-[11C]PK11195] and its metabolites in humans

    International Nuclear Information System (INIS)

    Greuter, Henri N.J.M.; van Ophemert, Patricia L.B.; Luurtsema, Gert; van Berckel, Bart N.M.; Franssen, Eric J.F.; Windhorst, Bert D.; Lammertsma, Adriaan A.

    2005-01-01

    (R)-[ 11 C]PK11195 is used as a positron emission tomography tracer for activated microglia in several neurological disorders. Quantification of specific binding requires a metabolite-corrected plasma input function. In this study, a high-performance liquid chromatography (HPLC) procedure with online solid phase extraction was modified for analyzing (R)-[ 11 C]PK11195 plasma samples, yielding total sample recoveries of more than 98%. When applied to human studies, the use of two HPLC systems enabled analysis of up to seven plasma samples under regular conditions. Online radioactivity detection was compared with offline sample measurements of HPLC profiles. Offline measurements provided the most reliable results especially for late plasma samples. In 10 patients, an average decrease of parent compound from 94.6% at 2.5 min to 45.2% at 1 h after administration was observed

  2. Synthesis, crystal structure and luminescent properties of one 3D Cd(II) coordination polymer [Cd(H3BPTC)2(bpy)]n (H4BPTC = 1,1'-biphenyl-2,2',6,6'-tetracarboxylic acid, bpy = 4,4'-bipyridine).

    Science.gov (United States)

    Mei, Chong-Zhen; Shan, Wen-Wen; Liu, Bing-Tao

    2011-10-15

    A new 3D metal-organic coordination polymer [Cd(H(3)BPTC)(2)(bpy)](n) (1) (H(4)BPTC = 1,1'-biphenyl-2,2',6,6'-tetracarboxylic acid, bpy =4,4'-bipyridine) has been synthesized and characterized by single X-ray diffraction and IR spectroscopy. The one-dimensional metal-organic chains of the title complex, namely [Cd(H(3)BPTC)(2)](n), are held together through hydrogen bonding and bridging "second" ligand 4,4'-bpy to give a three-dimensional metal-organic network. The thermal stability of complex 1 was studied by thermal gravimetric (TG) and differential thermal analysis (DTA). Compound 1 exhibits photoluminescence with an emission maximum at ca. 380 nm upon excitation at ca. 251 nm. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Synthesis and biological evaluation of [11C]MK-912 as an α2-adrenergic receptor radioligand for PET studies

    International Nuclear Information System (INIS)

    Shiue Chyngyann; Pleus, Richard C.; Shiue, Grace G.; Rysavy, Joseph A.; Sunderland, John J.; Cornish, Kurtis G.; Young, Steven D.; Bylund, David B.

    1998-01-01

    ABSTRACT. In vitro studies showed that MK-912 ((2S, 12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2H-benzo[b]furo [2,3-a]quinolizine)-2,4'-pyrimidin-2'-one) is a potent α 2 -adrenergic receptor antagonist with high affinity (K i = 0.42, 0.26 and 0.03 nM to α 2A , α 2B and α 2C , respectively) and high selectivity (α 2A /α 1A = 240; α 2A /D-1 = 3600; α 2A /D-2 3500; α 2A /5-HT 1 = 700; α 2A /5-HT 2 = 4100). The compound was labeled with 11 C and evaluated in rodents and monkey as a specific radioligand for studying α 2 -adrenergic receptors using PET. [ 11 C]MK-912 was synthesized by methylation of its desmethyl precursor, L-668,929, with [ 11 C]CH 3 I in (Bu 3 O)P=O at 85 deg. C for 8 min followed by purification with HPLC in 18% yield in a synthesis time of 45 min from end of bombardment (EOB). The specific activity was 0.83-0.93 Ci/μmol and the radiochemical purity was 97%. The initial uptake of [ 11 C]MK-912 in mouse brain, heart, lung, liver and kidney was high (5%, 4%, 5%, 17% and 8% per gram of organ, respectively, at 5 min postinjection) and the activities were then slowly cleared from these organs. The uptake of [ 11 C]MK-912 in rat olfactory tubercle, a brain region with high density of α 2 -adrenergic receptors, was reduced by 30%, and the ratio of radioactivity in olfactory tubercle/cerebellum was reduced from 2:1 to 1:1 by coinjection of [ 11 C]MK-912 with a potent α 2 -adrenergic receptor antagonist, atipamezole (3 mg/kg), indicating that compound 2 binds to α 2 -adrenergic receptors. However, a PET study in a rhesus monkey revealed that the initial influx of [ 11 C]MK-912 into various brain regions (cerebellum, cortex, olfactory tubercle and striatum) was high (0.02%/cc), and the radioactivity was then washed out slowly and without significantly differential retention in these brain regions. This, coupled with the fact that none of the high-density α 2 -adrenergic receptor brain regions exceeds a few millimeters in diameter

  4. Ethyl 27-oxo-15-oxa-2,20-diazahexacyclo[18.6.1.01,8.02,6.09,14.021,26]heptacosa-9,11,13,21,23,25-hexaene-7-carboxylate

    Directory of Open Access Journals (Sweden)

    Devadasan Velmurugan

    2013-01-01

    Full Text Available In the title compound, C27H30N2O4, the pyrrolidine ring adopts a twisted conformation. The indoline ring system is almost perpendicular to the mean plane of the pyrrolidine ring, making a dihedral angle of 81.7 (8°. In the crystal, molecules are linked into centrosymmetric dimers with graph-set motif R22(16 via pairs of C—H...O hydrogen bonds. The terminal ethyl group of the ester group is disordered over two sets of sites, with a site-occupancy ratio of 0.587 (11:0.413 (11.

  5. Theophylline–gentisic acid (1/1

    Directory of Open Access Journals (Sweden)

    Srinivasulu Aitipamula

    2009-09-01

    Full Text Available In the title 1:1 cocrystal, C7H8N4O2·C7H6O4, the anti-asthmatic drug theophylline (systematic name: 1,3-dimethyl-7H-purine-2,6-dione and a non-steroidal anti-inflammatory drug, gentisic acid (systematic name: 2,5-dihydroxybenzoic acid crystallize together, forming two-dimensional hydrogen-bonded sheets involving N—H...O and O—H...N hydrogen bonds. The overall crystal packing features π–π stacking interactions [centroid–centroid distance = 3.348 (1 Å]. The cocrystal described herein belongs to the class of pharmaceutical cocrystals involving two active pharmaceutical ingredients which has been relatively unexplored to date.

  6. Automated synthesis of 11C-carfentanil with 11C-choline module and micro PET imaging

    International Nuclear Information System (INIS)

    Zhang Jinming; Zhang Xiaojun; Tian Jiahe; Xu Zhihong; Xiang Xiaohui

    2011-01-01

    A simple modified home-made 11 C-choline module enabled to rapid and efficient synthesis 11 C-carfentanil ( 11 C-CFN) as CNS μ-opioid receptor imaging agent. The synthesis of 11 C-CFN was completed in a yield of 14.8 GBq within 18 min from 11 C-CO 2 on the choline module. The methylation took place from 4-piperidinecarboxylic acid, 4-[(1-oxopropyl) phenylamino]-l-(2-phenylethyl), sodium salt as precursor in DMSO solution. The radio- chemical yields were over 80% (n=55, decay-corrected and based on 11 CH 3 -triflate). The radiochemical purity was over 95% and the specific activities was over 1.4 × 10 14 Bq/g. The biologic activity of 11 C-CFN was confirmed with Micro PET/CT imaging. (authors)

  7. Synthesis, crystal structure and biological activity of a novel 1,2,3-thidiazole compound

    International Nuclear Information System (INIS)

    Ke, W.

    2013-01-01

    A new 1,2,3-thiadiazole compound was synthesized and characterized by 1H NMR, MS and HRMS. The crystal structure of the title compound (C/sub 12/H/sub 11/ClN/sub 2/O/sub 4/S/sub 2/, Mr = 346.80) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P-1 with a = 8.4425(17) A, b = 8.9801(18) A, c = 9.859(2) A, alpha = 84.36(3) degree, beta = 86.71(3)degree, lambda = 83.25(3) degree, V = 737.9(3)A3, Z 2, F(000) = 356, Dc = 1.561 g/cm/sup 3/, mu = 0.557 mm-1, the final R1 0.0380 and wR2 = 0.0982 for 2160 observed reflections with I > 2sigma(I). A total of 12585 reflections were collected, of which 2601 were independent (Rint 0.0364). The herbicidal activity of title compound was determined, the results showed the title compound displayed excellent herbicidal activity against Brassica campestris. (author)

  8. Synthesis of γ-amino[4-11C]butyric acid (GABA)

    International Nuclear Information System (INIS)

    Antoni, G.; Laangstroem, B.

    1989-01-01

    A one-pot synthesis of no-carrier added γ-amino[4- 11 C]butyric acid (GABA) starting with hydrogen [ 11 C]cyanide prepared from [ 11 C]carbon dioxide, is presented. Hydrogen [ 11 C]cyanide was trapped in tetrahydrofuran/potassium hydroxide in the presence of the amino polyether Krytofix 2.2.2. A Michael addition with ethyl acrylate followed by a selective reduction and hydrolysis of the resulting amino ester gave [4- 11 C]GABA. The radiochemical purity of GABA was higher than 99% and the decay corrected radiochemical yield was 60-65% based on the amount of H[ 11 C]CN used. The total synthesis time including purification was around 40 min, counted from the start of the Michael addition reaction. (Author)

  9. Radiosynthesis and biodistribution of a histamine H{sub 3} receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[{sup 11}C]benzyl]-morpholine: evaluation of a potential PET ligand

    Energy Technology Data Exchange (ETDEWEB)

    Airaksinen, Anu J. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Jablonowski, Jill A. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Mey, Margreet van der [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Barbier, Ann J. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Klok, Rob P. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Verbeek, Joost [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Schuit, Robert [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Herscheid, Jacobus D.M. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Leysen, Josee E. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Carruthers, Nicholas I. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Lammertsma, Adriaan A. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Windhorst, Albert D. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands)]. E-mail: bwindhorst@rnc.vu.nl

    2006-08-15

    The potent histamine H{sub 3} receptor antagonist JNJ-10181457 () was successfully labeled with {sup 11}C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28{+-}8%) and high specific radioactivity (56{+-}26 GBq/{mu}mol). The binding of [{sup 11}C] to H{sub 3} receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [{sup 11}C] in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H{sub 3} antagonists, JNJ-5207852 () and unlabeled Compound (), in a concentration-dependent manner. The biodistribution of [{sup 11}C] in rats was measured at 5, 10, 30 and 60 min. The uptake of [{sup 11}C] in regions rich in H{sub 3} receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [{sup 11}C] in the rat brain could not be blocked by pretreatment with either Compound () (30 min or 24 h pretreatment) or cold Compound () (30-min pretreatment). The biodistribution of [{sup 11}C] in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H{sub 3}(-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [{sup 11}C] could not specifically label H{sub 3} receptors in rodent brain in vivo. Possible causes are discussed.

  10. Synthesis of 2-[11C]cyano-isonicotinic acid hydrazide

    International Nuclear Information System (INIS)

    Somwardhana, C.W.; Sajjad, M.; Lambrecht, R.M.

    1990-01-01

    Isonicotinic acid hydrazide (isoniazid), a drug used in treating tuberculosis has been labelled with carbon-11 at the 2-position. The labelling synthesis starts with methyl isonicotinate treated with dimethyl sulfate. The resulting salt solution is loaded onto silica gel and dried, followed by treatment with carbon-11 labelled hydrocyanic acid. Work-up gave the labelled compound with an average 32% radiochemical yield. Subsequent treatment with hydrazine hydrate yielded isoniazid

  11. 1-Methoxy-1,1-diphenylbut-2-yne

    Directory of Open Access Journals (Sweden)

    Nadine Seidel

    2018-04-01

    Full Text Available In the title compound, C17H16O, the phenyl rings are twisted relative to each other at an angle of 85.9 (1°. The crystal structure features weak C—H...π interactions, which connect the molecules into a three-dimensional supramolecular network.

  12. Simplified PET measurement for evaluating histamine H{sub 1} receptors in human brains using [{sup 11}C]doxepin

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Hideki [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Kimura, Yuichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)]. E-mail: ukimura@ieee.org; Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Oda, Keiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Sasaki, Toru [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Tashiro, Manabu [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Yanai, Kazuhiko [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)

    2004-11-01

    The aim of this study was to develop simplified positron emission tomography measurement using [{sup 11}C]doxepin ([{sup 11}C]DOX) to evaluate histamine H{sub 1} receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [{sup 11}C]DOX, estimated quantitatively with a two-compartment model, and the [{sup 11}C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [{sup 11}C]DOX-H1R binding.

  13. 1,1-Dimethylbiguanidium(2+ dinitrate

    Directory of Open Access Journals (Sweden)

    Michaela Fridrichová

    2012-01-01

    Full Text Available In the crystal structure of the title compound, C4H13N52+·2NO3−, the main intermolecular interactions are the N—H...O hydrogen bonds between the cationic amino groups and the O atoms of the nitrate ions. All amino H atoms and nitrate O atoms are involved in the three-dimensional hydrogen-bond network. There are two graph-set motifs R22(8, which include the amino groups connected to the N atoms in the biguanide 3-, 4- and 5-positions, and the O atoms of a nitrate ion. They are extended along the a axis. An O atom of the second nitrate ion is involved in a graph-set motif C(4 that is a part of a helix-like N—H...O...H—N—H...O... chain oriented along the b axis. There are also two weak C—H...O interactions in the crystal structure.

  14. 26 CFR 11.412(c)-11 - Election with respect to bonds.

    Science.gov (United States)

    2010-04-01

    ... amount payable at maturity (or, in the case of a bond which is callable prior to maturity, the earliest... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Election with respect to bonds. 11.412(c)-11... OF 1974 § 11.412(c)-11 Election with respect to bonds. (a) In general. Section 412(c)(2)(B) provides...

  15. Synthesis of 11-14C-quetiapine, 11-14C-isoclotiapine and 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine[10-14C

    International Nuclear Information System (INIS)

    Naghi Saadatjoo; Mohsen Javaheri; Nuclear Science and Technology Research Institute, Tehran; Nader Saemian; Mohsen Amini

    2016-01-01

    Quetiapine is one of the most widely used antipsychotic drug which acts as an antagonist for multiple neurotransmitter receptor sites. 2-[2-(4-(Dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)ethoxy]ethanol (quetiapine) labeled with carbon-14 in 11-position has been synthesized as part of a 5-step sequence from anthranilic acid-[carboxy- 14 C]. We have presented a convenient synthetic pathway for labeling of quetiapine with carbon-14 by using one-pot procedures from a key thiazepin-11(10H)-one-[11- 14 C] by good radiochemical yield. And also isoclotiapine[11- 14 C], and 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine[10- 14 C], synthesized according to this route. (author)

  16. In vivo positron emission tomography studies on the novel nicotinic receptor agonist [11C]MPA compared with [11C]ABT-418 and (S)(-)[11C]nicotine in Rhesus monkeys

    International Nuclear Information System (INIS)

    Sihver, Wiebke; Fasth, Karl-Johan; Oegren, Matthias; Lundqvist, Hans; Bergstroem, Mats; Watanabe, Yasuyoshi; Laangstroem, Bengt; Nordberg, Agneta

    1999-01-01

    The novel 11 C-labeled nicotinic agonist (R,S)-1-[ 11 C]methyl-2(3-pyridyl)azetidine ([ 11 C]MPA) was evaluated as a positron emission tomography (PET) ligand for in vivo characterization of nicotinic acetylcholine receptors in the brain of Rhesus monkeys in comparison with the nicotinic ligands (S)-3-methyl-5-(1-[ 11 C]methyl-2-pyrrolidinyl)isoxazol ([ 11 C]ABT-418) and (S)(-)[ 11 C]nicotine. The nicotinic receptor agonist [ 11 C]MPA demonstrated rapid uptake into the brain to a similar extent as (S)(-) [ 11 C]nicotine and [ 11 C]ABT-418. When unlabeled (S)(-)nicotine (0.02 mg/kg) was administered 5 min before the radioactive tracers, the uptake of [ 11 C]MPA was decreased by 25% in the thalamus, 19% in the temporal cortex, and 11% in the cerebellum, whereas an increase was found for the uptake of (S)(-)[ 11 C]nicotine and [ 11 C]ABT-418. This finding indicates specific binding of [ 11 C]MPA to nicotinic receptors in the brain in a simple classical displacement study. [ 11 C]MPA seems to be a more promising radiotracer than (S)(-)[ 11 C]nicotine or [ 11 C]ABT-418 for PET studies to characterize nicotinic receptors in the brain

  17. [11C]TASP457, a novel PET ligand for histamine H3 receptors in human brain

    International Nuclear Information System (INIS)

    Kimura, Yasuyuki; Seki, Chie; Ikoma, Yoko; Ichise, Masanori; Kawamura, Kazunori; Takahata, Keisuke; Moriguchi, Sho; Nagashima, Tomohisa; Ishii, Tatsuya; Kitamura, Soichiro; Niwa, Fumitoshi; Endo, Hironobu; Yamada, Makiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya

    2016-01-01

    The histamine H 3 receptors are presynaptic neuroreceptors that inhibit the release of histamine and other neurotransmitters. The receptors are considered a drug target for sleep disorders and neuropsychiatric disorders with cognitive decline. We developed a novel PET ligand for the H 3 receptors, [ 11 C]TASP0410457 ([ 11 C]TASP457), with high affinity, selectivity and favorable kinetic properties in the monkey, and evaluated its kinetics and radiation safety profile for quantifying the H 3 receptors in human brain. Ten healthy men were scanned for 120 min with a PET scanner for brain quantification and three healthy men were scanned for radiation dosimetry after injection of 386 ± 6.2 MBq and 190 ± 7.5 MBq of [ 11 C]TASP457, respectively. For brain quantification, arterial blood sampling and metabolite analysis were performed using high-performance liquid chromatography. Distribution volumes (V T ) in brain regions were determined by compartment and graphical analyses using the Logan plot and Ichise multilinear analysis (MA1). For dosimetry, radiation absorbed doses were estimated using the Medical Internal Radiation Dose scheme. [ 11 C]TASP457 PET showed high uptake (standardized uptake values in the range of about 3 - 6) in the brain and fast washout in cortical regions and slow washout in the pallidum. The two-tissue compartment model and graphical analyses estimated V T with excellent identification using 60-min scan data (about 16 mL/cm 3 in the pallidum, 9 - 14 in the basal ganglia, 6 - 9 in cortical regions, and 5 in the pons), which represents the known distribution of histamine H 3 receptors. For parametric imaging, MA1 is recommended because of minimal underestimation with small intersubject variability. The organs with the highest radiation doses were the pancreas, kidneys, and liver. The effective dose delivered by [ 11 C]TASP457 was 6.9 μSv/MBq. [ 11 C]TASP457 is a useful novel PET ligand for the investigation of the density of histamine H 3

  18. Mass of 11Li from the 1H(11Li,9Li)3H reaction

    International Nuclear Information System (INIS)

    Roger, T.; Savajols, H.; Mittig, W.; Caamano, M.; Roussel-Chomaz, P.; Tanihata, I.; Alcorta, M.; Bandyopadhyay, D.; Bieri, R.; Buchmann, L.; Davids, B.; Galinski, N.; Howell, D.; Mills, W.; Mythili, S.; Openshaw, R.; Padilla-Rodal, E.; Ruprecht, G.; Sheffer, G.; Shotter, A. C.

    2009-01-01

    The mass of 11 Li has been determined from Q-value measurements of the 1 H( 11 Li, 9 Li) 3 H reaction. The experiment was performed at TRIUMF laboratory with the GANIL active target MAYA. Energy-energy and angle-angle kinematics reconstruction give a Q value of 8.119(22) MeV for the reaction. The derived 11 Li two-neutron separation energy is S 2n =363(22) keV

  19. 1,1′-{1,4-Phenylene bis[3-(6-chloro-2-methyl-4-phenylquinolin-3-yl-4,5-dihydro-1H-pyrazole-5,1-diyl]}dibutan-1-one

    Directory of Open Access Journals (Sweden)

    Allaoua Kedjadja

    2015-10-01

    Full Text Available A new polycyclic compound, 1,1′-{1,4-phenylene bis[3-(6-chloro-2-methyl-4-phenylquinolin-3-yl-4,5-dihydro-1H-pyrazole-5,1-diyl]}dibutan-1-one (3 has been synthesized by cyclocondensation of (2E,2′E-1,1′-bis(6-chloro-2-methyl-4-phenylquinolin-3-yl-3,3′-(1,4-phenylenediprop-2-en-1-one (2 and hydrazine hydrate in butanoic acid. The structure of this compound was established by elemental analysis, 1H-NMR, 13C-NMR, mass and IR spectroscopy.

  20. Test-retest reproducibility of dopamine D{sub 2/3} receptor binding in human brain measured by PET with [{sup 11}C]MNPA and [{sup 11}C]raclopride

    Energy Technology Data Exchange (ETDEWEB)

    Kodaka, Fumitoshi [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); Jikei University School of Medicine, Department of Psychiatry, Tokyo (Japan); Ito, Hiroshi [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); National Institute of Radiological Sciences, Biophysics Program, Molecular Imaging Center, Chiba (Japan); Kimura, Yasuyuki; Fujie, Saori; Takano, Harumasa; Fujiwara, Hironobu; Sasaki, Takeshi; Suhara, Tetsuya [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); Nakayama, Kazuhiko [Jikei University School of Medicine, Department of Psychiatry, Tokyo (Japan); Halldin, Christer; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden)

    2013-04-15

    Dopamine D{sub 2/3} receptors (D{sub 2/3}Rs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D{sub 2/3} {sup HIGH}), which has a high affinity for endogenous dopamine, and low-affinity state (D{sub 2/3} {sup LOW}). The density of D{sub 2/3} {sup HIGH} can be measured with (R)-2-{sup 11}CH{sub 3}O-N-n-propylnorapomorphine ([{sup 11}C]MNPA), while total density of D{sub 2/3} {sup HIGH} and D{sub 2/3} {sup LOW} (D{sub 2/3}Rs) can be measured with [{sup 11}C]raclopride using positron emission tomography (PET). Thus, the ratio of the binding potential (BP) of [{sup 11}C]MNPA to that of [{sup 11}C]raclopride ([{sup 11}C]MNPA/[{sup 11}C]raclopride) may reflect the proportion of the density of D{sub 2/3} {sup HIGH} to that of D{sub 2/3}Rs. In the caudate and putamen, [{sup 11}C]MNPA/[{sup 11}C]raclopride reflects the proportion of the density of D{sub 2} {sup HIGH} to that of D{sub 2}Rs. To evaluate the reliability of the PET paradigm with [{sup 11}C]MNPA and [{sup 11}C]raclopride, we investigated the test-retest reproducibility of non-displaceable BP (BP{sub ND}) measured with [{sup 11}C]MNPA and of [{sup 11}C]MNPA/[{sup 11}C]raclopride in healthy humans. Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [{sup 11}C]MNPA and [{sup 11}C]raclopride scans. BP{sub ND} values in the caudate and putamen were calculated. Test-retest reproducibility of BP{sub ND} of [{sup 11}C]MNPA and [{sup 11}C]MNPA/[{sup 11}C]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC). The absolute variability of [{sup 11}C]MNPA BP{sub ND} was 5.30 {+-} 3.96 % and 12.3 {+-} 7.95 % and the ICC values of [{sup 11}C]MNPA BP{sub ND} were 0.72 and 0.82 in the caudate and putamen, respectively. The absolute variability of [{sup 11}C]MNPA/[{sup 11}C]raclopride was 6.11 {+-} 3.68 % and 11.60 {+-} 5.70 % and the ICC values of [{sup

  1. 6a-Nitro-6-(2,2,7,7-tetramethyltetrahydro-3aH-bis[1,3]dioxolo[4,5-b:4′,5′-d]pyran-5-yl-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]pyrrolizine-11,11′-indeno[1,2-b]quinoxaline

    Directory of Open Access Journals (Sweden)

    T. Anuradha

    2014-01-01

    Full Text Available In the title compound, C39H38N4O8, the quinoxaline and indene subunits are essentially planar, with maximum deviations of 0.071 (2 and 0.009 (2 Å, respectively. The indenoquinoxaline system forms a dihedral angle of 72.81 (3° with the chromenopyrrolizine system. The two dioxolane rings, as well as the pyran ring of the chromeno group and the terminal pyrrolizine, each adopt an envelope conformation with O and C as flap atoms. The central pyrrolizine ring adopts a twisted conformation. Intramolecular C—H...O and C—H...N hydrogen bonds occur. The crystal structure exhibits C—H...O hydrogen bonds, and is further stablized by C—H...π interactions, forming a two-dimensional network along the bc plane.

  2. Comparative PET studies of the distribution of ( - )-3,4-methylenedioxy-N-[{sup 11}C]methamphetamine and ( - )-[{sup 11}C]methamphetamine in a monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Shiue Chyngyann; Shiue, Grace G.; Cornish, Kurtis G.; O' Rourke, Maria F

    1995-04-01

    Carbon-11 labeled ( - )-methamphetamine and ( - )-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [{sup 11}C]H{sub 3}I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/{mu}M. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of ( - )-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as ( - )-methamphetamine while only 3% remained as ( - )-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes.

  3. Synthesis and in vivo evaluation of [11C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors

    International Nuclear Information System (INIS)

    Dumont, Filip; Waterhouse, Rikki N.; Montoya, Julie A.; Mattner, Filomena; Katsifis, Andrew; Kegeles, Lawrence S.; Laruelle, Marc

    2003-01-01

    The synthesis and evaluation of [ 11 C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [ 11 C] methyl iodide afforded the title compound [ 11 C]zolpidem in a yield of 19.19 ± 3.23% in 41 ± 2 min in specific activities of 0.995-1.19 Ci/μmol (1.115 ± 0.105 Ci/μmol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 ± 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [ 11 C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors

  4. Synthesis and in vivo evaluation of [11C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors.

    Science.gov (United States)

    Dumont, Filip; Waterhouse, Rikki N; Montoya, Julie A; Mattner, Filomena; Katsifis, Andrew; Kegeles, Lawrence S; Laruelle, Marc

    2003-05-01

    The synthesis and evaluation of [(11)C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [(11)C] methyl iodide afforded the title compound [(11)C]zolpidem in a yield of 19.19 +/- 3.23% in 41 +/- 2 min in specific activities of 0.995-1.19 Ci/micromol (1.115 +/- 0.105 Ci/micromol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 +/- 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [(11)C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors.

  5. The synthesis of no-carrier-added [11C]urea from [11C]carbon dioxide and application to [11C]uracil synthesis

    International Nuclear Information System (INIS)

    Chakraborty, P.K.; Mangner, T.J.; Chugani, H.T.

    1997-01-01

    No-carrier-added [ 11 C]urea has been synthesized by bubbling cyclotron-produced [ 11 C]-carbon dioxide directly into a tetrahydrofuran solution of lithium bis(trimethylsilyl)amide, followed by hydrolysis of the C-11 labeled adduct with aqueous ammonium chloride. Using this simple, one-pot method, [ 11 C]urea was produced in 55-70% radiochemical yield (decay-corrected) in 16 min following end-of-bombardment (or in 10 min following the introduction of the [ 11 C]carbon dioxide. The [ 11 C]urea thus produced was converted to [ 11 C]uracil (carrier-added) in 40-75% decay-corrected radiochemical yield by condensation with diethyl malate in presence of fuming sulfuric acid. (author)

  6. Total synthesis of [2-11C]thymidine from [11C]urea: A tracer of choice for measurement of cellular proliferation using PET

    International Nuclear Information System (INIS)

    Labar, D.; Vander Borght, T.

    1990-01-01

    In preliminary studies of cellular proliferation with [methyl- 11 C]thymidine, the labelled degradative products mask the progressive incorporation of the tracer into DNA. The authors have developed a procedure for the synthesis of [2- 11 C]thymidine to circumvent this difficulty, using a [ 11 C]urea precursor

  7. N-[11C]methyl-3,4-methylenedioxyamphetamine (Ecstasy) and 2-methyl-N-[11C]methyl-4,5-methylenedioxyamphetamine. Synthesis and biodistribution studies

    International Nuclear Information System (INIS)

    Patt, M.; Machulla, H.J.; Guendisch, D.; Kovar, K.A.; Wuellner, U.; Blocher, A.

    1999-01-01

    In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA), 2 and 2,N-dimethyl-4,5-methylenedioxyamphetamine (MADAM-6) 4 were prepared for application in in-vivo PET studies by methylation of 3,4-methylenedioxyamphetamine (MDA) 1 and 2-methyl-4,5-methylenedioxyamphetamine 3 with [ 11 C]CH 3 I. The radiochemical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-11 on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors 1 or 3, thus obtaining radiochemical yields of 60% (based on produced [ 11 C]CH 3 I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed for [ 11 C]MDMA in contrast to a ratio of 3.7 for [ 11 C]MADAM-6. (author)

  8. Synthesis of O-[11C]acetyl CoA, O-[11C]acetyl-L-carnitine, and L-[11C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

    International Nuclear Information System (INIS)

    Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

    1997-01-01

    The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with 11 C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1- 11 C]acetyl CoA and O-[2- 11 C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1- 11 C]acetyl-L-carnitine and O-[2- 11 C]acetyl-L-carnitine in 70-80% yield, based on [1- 11 C]acetate or [2- 11 C]acetate, respectively. By an N-methylation reaction with [ 11 C]methyl iodide, L-[methyl- 11 C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl- 11 C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [ 11 C]methyl iodide. Initial data of the kinetics of the different 11 C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented

  9. 2-(2-Methyl-1,3-dioxolan-2-yl-1,1-diphenylethanol

    Directory of Open Access Journals (Sweden)

    Dennis P. Arnold

    2010-01-01

    Full Text Available The molecules of the title compound, C18H20O3, display an intramolecular O—H...O hydrogen bond between the hydroxy donor and a ketal O-atom acceptor. In the crystal, intermolecular C—H...π interactions connect adjacent molecules into chains parallel to the b axis.

  10. Crystal structure of 5-{4'-[(2-{2-[2-(2-ammonio-eth-oxy)eth-oxy]eth-oxy}eth-yl)carbamo-yl]-4-meth-oxy-[1,1'-biphen-yl]-3-yl}-3-oxo-1,2,5-thia-diazo-lidin-2-ide 1,1-dioxide: a potential inhibitor of the enzyme protein tyrosine phosphatase 1B (PTP1B).

    Science.gov (United States)

    Ruddraraju, Kasi Viswanatharaju; Hillebrand, Roman; Barnes, Charles L; Gates, Kent S

    2015-04-01

    The title compound, C24H32N4O8S, (I), crystallizes as a zwitterion. The terminal amine N atom of the [(2-{2-[2-(2-ammonio-eth-oxy)eth-oxy]eth-oxy}eth-yl)carbamo-yl] side chain is protonated, while the 1,2,5-thia-diazo-lidin-3-one 1,1-dioxide N atom is deprotonated. The side chain is turned over on itself with an intra-molecular N-H⋯O hydrogen bond. The 1,2,5-thia-diazo-lidin-3-one 1,1-dioxide ring has an envelope conformation with the aryl-substituted N atom as the flap. Its mean plane is inclined by 62.87 (8)° to the aryl ring to which it is attached, while the aryl rings of the biphenyl unit are inclined to one another by 20.81 (8)°. In the crystal, mol-ecules are linked by N-H⋯O and N-H⋯N hydrogen bonds, forming slabs lying parallel to (010). Within the slabs there are C-H⋯O and C-H⋯N hydrogen bonds and C-H⋯π inter-actions present.

  11. In vivo detection of central dopaminergic processes: studies with 1-C-11-dopa and C-11-labelled N-alkylated ADTN derivatives

    International Nuclear Information System (INIS)

    Werf, J.F. van der; Molen, H.D. Beerling-Van der; Paans, A.M.J.; Wiegman, T.; Korf, J.; Vaalburg, W.

    1982-01-01

    N-alkyl derivatives of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydro-naphthalene were labelled with 11 C by methylation with methyl iodide. They are dopamine agonists and have been found to bind, with high affinity, to dopamine receptors, in vitro and in vivo, after intracerebral administration. These compounds can pass the blood-brain barrier while the non-alkyl compound (ADTN) cannot. (U.K.)

  12. Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging

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    Genchel Tove

    2007-07-01

    Full Text Available Abstract Background The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171. Methods [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethyl-2-phenylpiperidin-3-amine (I and (2S,3S-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethylpiperidin-3-amine (II was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171. Results All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II had no specific binding in striatum. Ligand (I had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171. Conclusion The propyl-analogue (II cannot be used for detecting changes in NK1-ligand levels, while further studies should be

  13. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrapropynyloxy-2,8,14,20-tetrathiacalix[4]arene

    Directory of Open Access Journals (Sweden)

    Xiang-Gao Meng

    2009-12-01

    Full Text Available The title compound [systematic name: 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrapropynyloxy-2,8,14,20-tetrathiacalix[4]arene], C52H56O4S4, is an alkylated product bearing four propyne groups at the lower rim of a 5,11,17,23-tetra-tert-butyl-tetrathiacalix[4]arene. The molecule is located on a crystallographic twofold rotation axis, running through two S atoms and perpendicular to the long axis of the molecule. The four propyne groups, located in an alternate fashion above and below the mean plane of the four S atoms, are almost parallel to the calixarene long axis. The dihedral angle between the two crystallographically independent benzene rings is 86.77 (14°. Two tert-butyl groups are disordered over two positions with site occupancies of 0.59 (2 and 0.41 (2.

  14. Tert-butyl 3-oxo-2,3,4,5,6,7-hexahydro-1H-pyrazolo[4,3-c]pyridine-5-carboxylate

    Directory of Open Access Journals (Sweden)

    Tara Shahani

    2010-01-01

    Full Text Available In the title compound, C11H17N3O3, the pyrazole ring is approximately planar, with a maximum deviation of 0.005 (2 Å, and forms a dihedral angle of 5.69 (13° with the plane through the six atoms of the piperidine ring. In the crystal, pairs of intermolecular N—H...O hydrogen bonds form dimers with neighbouring molecules, generating R22(8 ring motifs. These dimers are further linked into two-dimensional arrays parallel to the bc plane by intermolecular N—H...O and C—H...O hydrogen bonds.

  15. Nido-Carborane building-block reagents. 2. Bulky-substituent (alkyl)2C2B4H6 derivatives and (C6H5)2C2B4H6: synthesis and properties

    International Nuclear Information System (INIS)

    Boyter, H.A. Jr.; Grimes, R.N.

    1988-01-01

    The preparation and chemistry of nido-2,3-R 2 C 2 C 2 B 4 H 6 carboranes in which R is n-butyl, isopentyl, n-hexyl, and phenyl was investigated in order to further assess the steric and electronic influence of the R groups on the properties of the nido-C 2 B 4 cage, especially with respect to metal complexation at the C 2 B 3 face and metal-promoted oxidative fusion. The three dialkyl derivatives were prepared from the corresponding dialkylacetylenes via reaction with B 5 H 9 and triethylamine, but the diphenyl compound could not be prepared in this manner and was obtained instead in a thermal reaction of B 5 H 9 with diphenylacetylene in the absence of amine. All four carboranes are readily bridge-deprotonated by NaH in THF, and the anions of the dialkyl species, on treatment with FeCl 2 and air oxidation, generate the respective R 4 C 4 B 8 H 8 carborane fusion products were R = n-C 4 H 9 , i-C 5 H 11 or n-C 6 H 13 . The diphenylcarborane anion Ph 2 C 2 B 4 H 5 - did not form detectable metal complexes with Fe 2+ , Co 2+ , or Ni 2+ , and no evidence of a Ph 4 C 4 B 8 H 8 fusion product has been found. Treatment of Ph 2 C 2 B 4 H 6 with Cr(CO) 6 did not lead to metal coordination of the phenyl rings, unlike (PhCH 2 ) 2 C 2 B 4 H 6 , which had previously been shown to form mono- and bis(tricarbonylchromium) complexes. However, the reaction of Ph 2 C 2 B 4 H 5 - , CoCl 2 , and (PhPCH 2 ) 2 did give 1,1-(Ph 2 PCH 2 ) 2 -1-Cl-1,2,3-Co(Ph 2 C 2 B 4 H 4 ), the only case in which metal complexation of the diphenylcarborane was observed. 14 references, 3 figures, 3 tables

  16. (E-N-[2-(9-Fluorenylidene-3a,5,7-trimethyl-3,3a-dihydro-2H-indol-3-ylidene]-2,4,6-trimethylaniline

    Directory of Open Access Journals (Sweden)

    Norihiro Tokitoh

    2008-02-01

    Full Text Available The title compound, C33H30N2, has an E configuration at the imine double bond. The angle between the least-squares planes of the imine C=N—C group and the benzene ring of the 2,4,6-trimethylphenyl substituent is 85.38 (11°. The crystal structure is sustained mainly by intermolecular π–π interactions (3.510 Å between the two fluorene rings and some C—H...π interactions.

  17. Synthesis of N1'-([11C]methyl)naltrindole ([11C]MeMNTI): a radioligand for positron emission tomographic studies of delta opioid receptors

    International Nuclear Information System (INIS)

    Lever, J.R.; Dannals, R.F.; Kinter, C.M.; Mathews, W.B.

    1995-01-01

    A delta opioid receptor antagonist, Nl'-methylnaltrindole (MeNTI), has been labeled with carbon-11. The precursor for radiolabeling was prepared in 71% yield by benzylation of the phenolic moiety of naltrindole. Alkylation of the indole nitrogen using [ 11 C]iodomethane and aqueous tetra(n-butyl)ammonium hydroxide at 80 o C in dimethylformamide followed by hydrogenolysis (H 2 , 10% Pd-C) of the benzyl protecting group gave [ 11 C]MeNTI. The average (n = 10) time for radiosynthesis, HPLC purification and formulation was 24 min from end-of-bombardment. [ 11 C]MeNTI of high radiochemical purity was obtained at end-of-synthesis with an average specific activity of 2050 mCi/μmol and radiochemical yield, based on [ 11 C]iodomethane, of 6%. (Author)

  18. Synthesis of [14C]-labelled eicosa-5,8,11-triynoic acid and conversion to anti-inflammatory amides

    International Nuclear Information System (INIS)

    Pilgrim, W.R.; Nedoncelle, P.; Shroot, B.; Maignan, J.; Restle, S.

    1991-01-01

    A four step synthesis of [5,6- 14 C]-eicosa-5,8,11-triynoic acid from [ 14 C]-labelled acetylene is described. [ 14 C 2 ]-acetylene was converted to 5-chloro-[1,2- 14 C]-pentyne via reaction of its monolithium salt with 3-bromo-1-chloropropane. The doubly labelled 5-chloropentyne thus obtained was transformed to [5,6- 14 C]-hex-5-ynoic acid which was then coupled with 1-chloro-tetradeca-2,5-diyne to give the title compound. Using 2-(2-aminoethoxy)ethanol and 1-(2-hydroxyethyl)piperazine, amides which had previously been found to be potent inhibitors of the 5-lipoxygenase enzyme, were prepared from [ 14 C-labelled eicosatriynoic acid by way of acylimidazole chemistry. (author)

  19. C-11 production with MC-50 cyclotron and synthesis of L-[11C-methyl] methionine

    International Nuclear Information System (INIS)

    Kim, Sang Wook; Hur, Min Goo; Yang, Seung Dae; Ahn, Soon Hyuk; Chun, Kweon Soo

    2003-01-01

    L-[ 11 C-methyl] methionine was prepared via no-carrier-added(nca) fast S-alkylation of L-homocysteine with [ 11 C]CH 3 I using solid support (Al 2 O 3 /KF)at room temperature in ethanol. The radiochemical yield of methylation was 90.2%. After reaction, no radiochemical impurity was detected but traces of L-homocysteine precursor were monitored by UV detector. The purification was archived by passing successively through a C 18 and alumina sep-pak. the radiochemical purity of L-[ 11 C-methyl] methionine was over 98% after purification and total elapsed time to prepare was 10min from [ 11 C]CH 3 I delivery

  20. Crystal structure of poly[[μ-1,1′-(butane-1,4-diylbis(1H-benzimidazole-κ2N3:N3′]{μ-4,4′-[1,4-phenylenebis(oxy]dibenzoato-κ4O,O′:O′′,O′′′}cobalt(II

    Directory of Open Access Journals (Sweden)

    Chen Xie

    2015-06-01

    Full Text Available In the title compound, [Co(C20H12O6(C18H18N4]n, the CoII atom, located on a twofold rotation axis, is hexacoordinated to four O from two bis-bidentate 4,4′-[phenylenebis(oxy]dibenzoate (L ligands and two N atoms from two 1,1′-(butane-1,4-diylbis(1H-benzimidazole (bbbm ligands, forming a distorted octahedral cis-N2O4 coordination environment. Polymeric zigzag chains along [102] are built up by the bridging L ligands. These chains are additionally connected by the bbbm ligands to produce a two-dimensional coordination polymer parallel too (010.

  1. (3-Aminophenyldiphenylphosphine oxide–2-propanol (1/1

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    Jafar Attar Gharamaleki

    2008-03-01

    Full Text Available The title compound, C18H16NOP·C3H8O, was synthesized by the reduction of (3-nitrophenyldiphenylphosphine oxide in the presence of 2-propanol as recrystallization solvent. There are two molecules in the asymmetric unit. Each P atom is tetracoordinated by three C and one O atom from two phenyl fragments, one aniline group and one double-bonded O atom in a distorted tetrahedral geometry. C—H...π and N—H...π interactions are present. In the crystal structure, a wide range of non-covalent interactions consisting of hydrogen bonding [of the types of O—H...O, N—H...O and C—H...O, with D...A distances ranging from 2.680 (3 to 3.478 (3 Å] and π–π [centroid–centroid distance of 3.7720 (15 Å] stacking interactions connect the various components into a supramolecular structure.

  2. 5-[(E-(2-Hydroxybenzylideneamino]-1H-1,3-benzimidazole-2(3H-thione

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-01-01

    Full Text Available There are two molecules in the asymmetric unit of the title compound, C14H11N3OS. In each, the benzimidazole ring system is essentially planar, with maximum deviations of 0.010 (2 and 0.006 (2 Å, and makes dihedral angles of 8.70 (9 and 13.75 (8°, respectively, with the hydroxy-substituted benzene rings. Each molecule adopts an E configuration about the central C=N double bond. In the crystal, the two independent molecules are connected via intermolecular N—H...S hydrogen bonds, forming dimers. Furthermore, the dimers are connected by N—H...O hydrogen bonds into molecular ribbons along the c axis. There is an intramolecular O—H...N hydrogen bond in each molecule, which generates an S(6 ring motif.

  3. 5-[(3-Fluorophenyl(2-hydroxy-6-oxocyclohex-1-en-1-ylmethyl]-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H-dione

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    Assem Barakat

    2016-09-01

    Full Text Available 5-[(3-Fluorophenyl(2-hydroxy-6-oxocyclohex-1-en-1-yl-methyl]-6-hydroxy-1,3-di-methylpyrimidine-2,4(1H,3H-dione 3 was synthesized via a multicomponent reaction. The Aldol–Michael addition reactions of N,N-dimethylbarbituric acid, cyclohexane-1,3-dione, and 3-fluorobenzaldehyde in aqueous solution gave the product in high yield. The molecular structure of the compound was confirmed by spectroscopic methods and X-ray crystallography. The title compound (C19H19FN2O5·H2O crystallizes in the Monoclinic form, P21/c, a = 7.8630 (5 Å, b = 20.0308 (13 Å, c = 11.3987 (8 Å, β = 104.274 (3°, V = 1739.9 (2° Å3, Z = 4, Rint = 0.117, wR(F2 = 0.124, T = 100 K.

  4. In vivo evaluation of alpha7 nicotinic acetylcholine receptor agonists [11C]A-582941 and [11C]A-844606 in mice and conscious monkeys.

    Directory of Open Access Journals (Sweden)

    Jun Toyohara

    Full Text Available BACKGROUND: The alpha7 nicotinic acetylcholine receptors (nAChRs play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. The goal of this study was to evaluate the two carbon-11-labeled alpha7 nAChR agonists [(11C]A-582941 and [(11C]A-844606 for their potential as novel positron emission tomography (PET tracers. METHODOLOGY/PRINCIPAL FINDINGS: The two tracers were synthesized by methylation of the corresponding desmethyl precursors using [(11C]methyl triflate. Effects of receptor blockade in mice were determined by coinjection of either tracer along with a carrier or an excess amount of a selective alpha7 nAChR agonist (SSR180711. Metabolic stability was investigated using radio-HPLC. Dynamic PET scans were performed in conscious monkeys with/without SSR180711-treatment. [(11C]A-582941 and [(11C]A-844606 showed high uptake in the mouse brain. Most radioactive compounds in the brain were detected as an unchanged form. However, regional selectivity and selective receptor blockade were not clearly observed for either compound in the mouse brain. On the other hand, the total distribution volume of [(11C]A-582941 and [(11C]A-844606 was high in the hippocampus and thalamus but low in the cerebellum in the conscious monkey brain, and reduced by pretreatment with SSR180711. CONCLUSIONS/SIGNIFICANCE: A nonhuman primate study suggests that [(11C]A-582941 and [(11C]A-844606 would be potential PET ligands for imaging alpha7 nAChRs in the human brain.

  5. Synthesis and in vivo evaluation of [{sup 11}C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dumont, Filip; Waterhouse, Rikki N. E-mail: rnw7@columbia.edu; Montoya, Julie A.; Mattner, Filomena; Katsifis, Andrew; Kegeles, Lawrence S.; Laruelle, Marc

    2003-05-01

    The synthesis and evaluation of [{sup 11}C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [{sup 11}C] methyl iodide afforded the title compound [{sup 11}C]zolpidem in a yield of 19.19 {+-} 3.23% in 41 {+-} 2 min in specific activities of 0.995-1.19 Ci/{mu}mol (1.115 {+-} 0.105 Ci/{mu}mol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 {+-} 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [{sup 11}C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors.

  6. New alkali-metal- and 2-phenethylamine-intercalated superconductors Ax(C8H11N)yFe1-zSe (A = Li, Na) with the largest interlayer spacings and Tc ∼ 40 K

    International Nuclear Information System (INIS)

    Hatakeda, Takehiro; Noji, Takashi; Sato, Kazuki; Kawamata, Takayuki; Kato, Masatsune; Koike, Yoji

    2016-01-01

    New FeSe-based intercalation superconductors, A x (C 8 H 11 N) y Fe 1-z Se (A = Li, Na), with T c = 39-44 K have been successfully synthesized via the intercalation of alkali metals and 2-phenethylamine into FeSe. The interlayer spacings, namely, the distances between neighboring Fe layers, d, of A x (C 8 H 11 N) y Fe 1-z Se (A = Li, Na) are 19.04(6) and 18.0(1) Å, respectively. These d values are the largest among those of the FeSe-based intercalation compounds and are understood to be due to the intercalation of two molecules of 2-phenethylamine in series perpendicular to the FeSe layers. It appears that the relationship between T c and d in the FeSe-based intercalation superconductors is not domic but T c is saturated at ∼45 K, which is comparable to the T c values of single-layer FeSe films, for d ≥ 9 Å. (author)

  7. Semi-automated preparation of a 11C-labelled antibiotic - [N-methyl-11C]erythromycin A lactobionate

    International Nuclear Information System (INIS)

    Pike, V.W.; Palmer, A.J.; Horlock, P.L.; Liss, R.H.

    1984-01-01

    A fast semi-automated method is described for labelling the antibiotic, erythromycin A (1), with the short-lived positron-emitting radionuclide, 11 C(tsub(1/2)=20.4 min), in order to permit the non-invasive study of its tissue uptake in vivo. Labelling was achieved by the fast reductive methylation of N-demethylerythromycin A (2) with [ 11 C]formaldehyde, itself prepared from cyclotron-produced [ 11 C]-carbon dioxide. Rapid chemical and radiochemical purification of the [N-methyl- 11 C]erythromycin A (3) were achieved by HPLC and verified by TLC with autoradiography. The purified material was formulated for human i.v. injection as a sterile apyrogenic solution of the lactobionate salt. The preparation takes 42 min from the end of radionuclide production and from [ 11 C]carbon dioxide produces [N-methyl- 11 C]erythromycin A lactobionate in 4-12% radiochemical yield, corrected for radioactive decay. (author)

  8. 12C(n , 2 n )11C cross section from threshold to 26.5 MeV

    Science.gov (United States)

    Yuly, M.; Eckert, T.; Hartshaw, G.; Padalino, S. J.; Polsin, D. N.; Russ, M.; Simone, A. T.; Brune, C. R.; Massey, T. N.; Parker, C. E.; Fitzgerald, R.; Sangster, T. C.; Regan, S. P.

    2018-02-01

    The 12C(n ,2 n )11C cross section was measured from just below threshold to 26.5 MeV using the Pelletron accelerator at Ohio University. Monoenergetic neutrons, produced via the 3H(d ,n )4He reaction, were allowed to strike targets of polyethylene and graphite. Activation of both targets was measured by counting positron annihilations resulting from the β+ decay of 11C. Annihilation gamma rays were detected, both in coincidence and singly, using back-to-back NaI detectors. The incident neutron flux was determined indirectly via 1H(n ,p ) protons elastically scattered from the polyethylene target. Previous measurements fall into upper and lower bands; the results of the present measurement are consistent with the upper band.

  9. Hardness in high temperature of steels ABNT H11 and ABNT H11 modified with niobium

    International Nuclear Information System (INIS)

    Goncalves, R.A.

    1984-01-01

    A method to measure the hardness of metallic materials was developed. The heating was done by the Joule effect heat dissipation in the sample, that is like an electrical resistor. A diamond penetrator with a revolution paraboloid format was used, that assure a linear relation between the load applyed and the penetration deep. Hardness tests were make in the range of 25 - 600 0 C, in the steels ABNT H11 and ABNT H11 modified with niobium, with the simultaneous register of the applied force, penetration deep and temperature. (E.G.) [pt

  10. 5-Isobutyl-4-phenylsulfonyl-1H-pyrazol-3(2H-one

    Directory of Open Access Journals (Sweden)

    M. Venkatesh

    2010-12-01

    Full Text Available The title compound, C13H16N2O3S, consists of two crystallographically independent molecules with similar geometries and exists in a keto form, the C=O bond lengths being 1.267 (2 and 1.254 (2 Å. In both molecules, the pyrazole rings are approximately planar, with maximum deviations of 0.017 (2 and 0.010 (2 Å, and the dihedral angles between the pyrazole and phenyl rings are 83.63 (11 and 70.07 (12°. In one molecule, an intramolecular C—H...O hydrogen bond with an S(6 ring motif is observed. In the crystal, intermolecular N—H...O and C—H...O hydrogen bonds link the molecules into two-dimensional networks parallel to the ab plane.

  11. The 1:1 co-crystal of triphenyl(2,3,5,6-tetrafluorobenzylphosphonium bromide and 1,1,2,2-tetrafluoro-1,2-diiodoethane

    Directory of Open Access Journals (Sweden)

    Gabriella Cavallo

    2014-01-01

    Full Text Available The title compound, C25H18F4P+·Br−·C2F4I2, is a 1:1 co-crystal of triphenyl(2,3,5,6-tetrafluorobenzylphosphonium (TTPB bromide and 1,1,2,2-tetrafluoro-1,2-diiodoethane (TFDIE. The crystal structure consists of a framework of TTPB cations held together by C—H...Br interactions. In this framework, infinite channels along [100] are filled by TFDIE molecules held together in infinite ribbons by short F...F [2.863 (22.901 (2Å] interactions. The structure contains halogen bonds (XB and hydrogen bonds (HB in the bromide coordination sphere. TFDIE functions as a monodentate XB donor as only one I atom is linked to the Br− anion and forms a short and directional interaction [I...Br− 3.1798 (7 Å and C—I...Br− 177.76 (5°]. The coordination sphere of the bromide anion is completed by two short HBs of about 2.8 Å (for H...Br with the acidic methylene H atoms and two longer HBs of about 3.0 Å with H atoms of the phenyl rings. Surprisingly neither the second iodine atom of TFDIE nor the H atom on the tetrafluorophenyl group make any short contacts.

  12. Cloning of cDNA encoding steroid 11β-hydroxylase (P450c11)

    International Nuclear Information System (INIS)

    Chua, S.C.; Szabo, P.; Vitek, A.; Grzeschik, K.H.; John, M.; White, P.C.

    1987-01-01

    The authors have isolated bovine and human adrenal cDNA clones encoding the adrenal cytochrome P-450 specific for 11β-hydroxylation (P450c11). A bovine adrenal cDNA library constructed in the bacteriophage λ vector gt10 was probed with a previously isolated cDNA clone corresponding to part of the 3' untranslated region of the 4.2-kilobase (kb) mRNA encoding P450c11. Several clones with 3.2-kb cDNA inserts were isolated. Sequence analysis showed that they overlapped the original probe by 300 base pairs (bp). Combined cDNA and RNA sequence data demonstrated a continuous open reading frame of 1509 bases. P450c11 is predicted to contain 479 amino acid residues in the mature protein in addition to a 24-residue amino-terminal mitochondrial signal sequence. A bovine clone was used to isolate a homologous clone with a 3.5-kb insert from a human adrenal cDNA library. A region of 1100 bp was 81% homologous to 769 bp of the coding sequence of the bovine cDNA except for a 400-bp segment presumed to be an unprocessed intron. Hybridization of the human cDNA to DNA from a panel of human-rodent somatic cell hybrid lines and in situ hybridization to metaphase spreads of human chromosomes localized the gene to the middle of the long arm of chromosome 8. These data should be useful in developing reagents for heterozygote detection and prenatal diagnosis of 11β-hydroxylase deficiency, the second most frequent cause of congenital adrenal hyperplasia

  13. Evaluation of in vivo selective binding of [11C]doxepin to histamine H1 receptors in five animal species

    International Nuclear Information System (INIS)

    Ishiwata, Kiichi; Kawamura, Kazunori; Wang Weifang; Tsukada, Hideo; Harada, Norihiro; Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Iwata, Ren; Yanai, Kazuhiko

    2004-01-01

    The specific binding of [ 11 C]doxepin, which has been used as a radioligand for mapping histamine H 1 receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [ 11 C]doxepin uptake was reduced by treatment with cold doxepin and two H 1 receptor antagonists, but not with H 2 /H 3 antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H 1 antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig

  14. Investigation of tautomeric transformations of adducts of 7,8-dicarba-nido-undecaborana(11) with derivatives of pyridine by 11B NMR spectroscopy method

    International Nuclear Information System (INIS)

    Volkov, O.V.; Il'inchik, E.A.; Volkov, V.V.

    1999-01-01

    Tautomeric transformations are investigated in solutions of o-carborane(12) derivatives 7,8-C 2 B 9 H 11 ·Py(X), where Py(X)=4-picoline (4-CH 3 -C 5 H 4 N), 3-picoline (3-CH 3 -C 5 H 4 N), 4-stilbazol (4-C 6 H 5 -C 2 H 2 -C 5 H 4 N), 3-bromopyridine (3-Br-C 5 H 4 N) and 7,8-C 2 B 9 H 10 I·C 5 H 5 N. Uncovered tautomeric transformations are bound with migration of bridge hydrogen of C 2 B 9 H 11 cluster assisting in structure of these compounds. Signal of boron nuclei in 11 B NMR spectra is observed in the region of high field of spectrum if the nearest two atoms of boron are bounded by bridge hydrogen additionally. That permits to fix happening dynamic structural transformations of adducts investigated. The dependence of tautomeric equilibrium on nature of substituents introduced in heterocyclic ligand and carborane cluster. Increase of electron-acceptor properties of substituent induces displacement of equilibrium in the direction of tautomer bridge hydrogen in which is removed from boron atom bounded with substituent [ru

  15. Radiosynthesis of 7-chloro-N, N-dimethyl-5-[11C] methyl-4-oxo-3-phenyl-3, 5-dihydro-4H pyridazino [4, 5-b]indole-1-acetamide, [11C]SSR180575, a novel radioligand for imaging the TSPO (peripheral benzodiazepine receptor) with PET

    International Nuclear Information System (INIS)

    Thominiaux, C.; Damont, A.L.; Kuhnast, B.; Demphel, St.; Le Helleix, St.; Chauveau, F.; Boutin, H.; Van Camp, N.; Boisgard, R.; Tavitian, B.; Dolle, F.; Boisnard, S.; Rivron, L.; Roy, S.; Allen, J.; Chauveau, F.; Boutin, H.; Van Camp, N.; Boisgard, R.; Tavitian, B.; Rooney, T.; Benavides, J.; Hantraye, Ph.

    2010-01-01

    SSR180575 (7-chloro-N, N, 5-trimethyl-4-oxo-3-phenyl-3, 5-dihydro-4H-pyridazino [4, 5-b]indole-1-acetamide) is the lead compound of an original pyridazino-indole series of potent and highly selective TSPO (peripheral benzodiazepine receptor) ligands. Isotopic labeling of SSR180575 with the short-lived positron-emitter carbon-11 (T1/2: 20.38 min) at its 5-methyl-pyridazino[4, 5-b]indole moiety as well as at its N, N-dimethylacetamide function by methylation of the corresponding nor-analogues was investigated. Best results in terms of radiochemical yields and purities were obtained for the preparation of [indole-N-methyl- 11 C]SSR180575, where routine production batches of 4.5-5.0 GBq of radiochemically pure (499%) i.v. injectable solutions (specific radioactivities: 50-90 GBq/μmol) could be prepared within a total synthesis time of 25 min (HPLC purification included) starting from a 55 GBq [ 11 C]CO 2 cyclotron production batch (non decay-corrected overall radiochemical yields: 8-9%). The process comprises (1) trapping at -10 C of [ 11 C]methyl triflate in DMF (300 μl) containing 0.2-0.3 mg of the indole precursor for labeling and 4 mg of K 2 CO 3 (excess); (2) heating at 120 C for 3 min; (3) dilution of the residue with 0.5 ml of the HPLC mobile phase and (4) purification using semi-preparative reversed phase HPLC (Zorbax R SB-C-18). In vivo pharmacological properties of [indole-N-methyl- 11 C]SSR180575 as a candidate for imaging neuro-inflammation with positron emission tomography are currently evaluated. (authors)

  16. Synthesis of ( sup 14 C)-labelled eicosa-5,8,11-triynoic acid and conversion to anti-inflammatory amides

    Energy Technology Data Exchange (ETDEWEB)

    Pilgrim, W R; Nedoncelle, P; Shroot, B [Centre International de Recherches Dermatologiques Galderma, Valbonne (France); Maignan, J; Restle, S [L' Oreal, Lab. de Recherches Fondamentales, Aulnay sous Bois, (France)

    1991-07-01

    A four step synthesis of (5,6-{sup 14}C)-eicosa-5,8,11-triynoic acid from ({sup 14}C)-labelled acetylene is described. ({sup 14}C{sub 2})-acetylene was converted to 5-chloro-(1,2-{sup 14}C)-pentyne via reaction of its monolithium salt with 3-bromo-1-chloropropane. The doubly labelled 5-chloropentyne thus obtained was transformed to (5,6-{sup 14}C)-hex-5-ynoic acid which was then coupled with 1-chloro-tetradeca-2,5-diyne to give the title compound. Using 2-(2-aminoethoxy)ethanol and 1-(2-hydroxyethyl)piperazine, amides which had previously been found to be potent inhibitors of the 5-lipoxygenase enzyme, were prepared from ({sup 14}C)-labelled eicosatriynoic acid by way of acylimidazole chemistry. (author).

  17. The determination of unchanged [11C]diprenorphine, [11C]L-deprenyl and [11C]raclopride in plasma by HPLC

    International Nuclear Information System (INIS)

    Luthra, S.K.; Turton, D.R.; Price, G.; Ahier, R.; Martin, F.; Hume, S.; Cremer, J.

    1990-01-01

    In PET studies a knowledge of the fraction of radioactivity in plasma representing unchanged 11 C-labelled ligand/tracer is essential for correction of the arterial plasma input curve. A number of different approaches (e.g. HPLC and TLC/OPTLC) to the determination of unchanged radio-ligand/tracer have been reported for 11 C-labelled carfentanil, raclopride and L-deprenyl and for 76 Br-labelled bromolisuride. The authors report here how they have applied the simple work-up and analytical procedure, originally reported for [ 11 C]carfentanil, to establish the percentage of unmchanged 11 C-labelled diprenorphine, L-deprenyl and raclopride in human and animal plasma as a function of time

  18. 12-Benzoyl-2-methylnaphtho[2,3-b]indolizine-6,11-dione

    Directory of Open Access Journals (Sweden)

    Yun Liu

    2011-06-01

    Full Text Available In the title compound, C24H15NO3, the fused naphthaquinone–pyrrole unit is approximately planar, the naphthaquinone ring system making a dihedral angle of 2.91 (10° with the pyrrole ring. The plane of the pyrrole ring makes a dihedral angle 61.64 (14° with that of the benzene ring of the benzoylmethylene group. The crystal structure is stablized by intramolecular C—H...O interactions.

  19. 1,1′-(Hexane-1,6-diylbis(indoline-2,3-dione

    Directory of Open Access Journals (Sweden)

    Fatima Zahrae Qachchachi

    2016-04-01

    Full Text Available The molecule of the title compound, C22H20N2O4, is situated on a crystallographic centre of symmetry. The two indoline-2,3-dione fragments are linked by a hexylene group at each N atom. In the crystal, supramolecular layers propagating in the ac plane are formed via C—H...O hydrogen bonds.

  20. Enzymatic synthesis of 11C-pyruvic acid and 11C-L-lactic acid

    International Nuclear Information System (INIS)

    Cohen, M.B.; Spolter, L.; Chang, C.C.; Cook, J.S.; Macdonald, N.S.

    1980-01-01

    L-Lactic acid is formed as the end product of glycolysis under anaerobic conditions in all cells, but this reaction is of special significance in the myocardium. L-Lactic acid is reversibly formed from and is in equilibrium with myocardial pyruvic acid, which is its sole metabolic pathway. 11 C-Pyruvic acid is synthesized from 11 C carbon dioxide using pyruvate-ferredoxin oxidoreductase and coenzymes. The 11 C-pyruvic acid is then converted to 11 -L-lactic acid by lactic acid dehydrogenase. The availability of 11 C-pyruvic acid and 11 C-L-lactic acid will permit the in vivo investigation of lactate metabolism. (author)

  1. Rapid labelling of radiopharmaceuticals using 11CO2 and 11CH4

    International Nuclear Information System (INIS)

    Crouzel, C.

    1988-07-01

    In the past two decades, much effort has been devoted to the development of new molecules, labelled with β+ emitters usable for Positron Emission Tomography. Gaseous forms of 11 C ( 11 CO 2 or 11 CH 4 ) must be converted to a reactive form known as a ''radioactive precursor'': 11 C-methanol, 11 C-formaldehyde, 11 C-acetone, 11 C-phosgene, 11 C-diazomethane, 11 C-methylamine. These precursors are used to label radiopharmaceuticals. Few examples are given: 11 C-prazosin, 11 C-CGP 12177, 11 C-pindolol. Such synthesis procedures require strong initial activity (1.5 Ci). The processes are therefore remotely controlled or automated, and confined to shielded cells. Small laboratory robots have lately been introduced for this type of production

  2. A novel organic–inorganic hybrid with Anderson type polyanions as building blocks: (C{sub 6}H{sub 10}N{sub 3}O{sub 2}){sub 2}Na(H{sub 2}O){sub 2}[Al(OH){sub 6}Mo{sub 6}O{sub 18}]·6H{sub 2}O

    Energy Technology Data Exchange (ETDEWEB)

    Thabet, Safa, E-mail: safathabet@hotmail.fr [Laboratoire de matériaux et cristallochimie, Département de chimie, Institut Supérieur des Sciences Appliquées et Technologier, Avenue El Mourouj, 5111 Mahdia (Tunisia); Ayed, Brahim, E-mail: brahimayed@yahoo.fr [Laboratoire de matériaux et cristallochimie, Département de chimie, Institut Supérieur des Sciences Appliquées et Technologier, Avenue El Mourouj, 5111 Mahdia (Tunisia); Haddad, Amor [Laboratoire de matériaux et cristallochimie, Département de chimie, Institut Supérieur des Sciences Appliquées et Technologier, Avenue El Mourouj, 5111 Mahdia (Tunisia)

    2012-11-15

    Graphical abstract: Display Omitted Highlights: ► Synthesis of a novel inorganic–organic hybrid compound based on Anderson polyoxomolybdates. ► Characterization by X-ray diffraction, IR and UV–Vis spectroscopies of the new compound. ► Potential applications in catalysis, biochemical analysis and electrical conductivity of the organic–inorganic compound. -- Abstract: A new organic–inorganic hybrid compound based on Anderson polyoxomolybdates, (C{sub 6}H{sub 10}N{sub 3}O{sub 2}){sub 2}Na(H{sub 2}O){sub 2}[Al(OH){sub 6}Mo{sub 6}O{sub 18}]·6H{sub 2}O (1) have been isolated by the conventional solution method and characterized by single-crystal X-ray diffraction, infrared, ultraviolet spectroscopy and Thermogravimetric Analysis (TGA). This compound crystallized in the triclinic system, space group P−1, with a = 94.635(1) Å, b = 10.958(1) Å, c = 11.602(1) Å, α = 67.525(1)°, β = 71.049(1)°, γ = 70.124(1)° and Z = 1. The crystal structures of the compounds exhibit three-dimensional supramolecular assembly based on the extensive hydrogen bonding interactions between organic cations, sodium cations, water molecules and Anderson polyoxoanions. The infrared spectrum fully confirms the X-ray crystal structure and the UV spectrum of the title compound exhibits an absorption peak at 210 nm.

  3. Reliable set-up for in-loop 11C-carboxylations using Grignard reactions for the preparation of [carbonyl-11C]WAY-100635 and [11C]-(+)-PHNO

    International Nuclear Information System (INIS)

    Rami-Mark, Christina; Ungersboeck, Johanna; Haeusler, Daniela; Nics, Lukas; Philippe, Cecile; Mitterhauser, Markus; Willeit, Matthaeus; Lanzenberger, Rupert; Karanikas, Georgios; Wadsak, Wolfgang

    2013-01-01

    Aim of this work was the implementation of a generalized in-loop synthesis for 11 C-carboxylations and subsequent 11 C-acylations on the TRACERlab FxC Pro platform. The set-up was tested using [carbonyl- 11 C]WAY-100635 and, for the first time, [ 11 C]-(+)-PHNO. Its general applicability could be demonstrated and both [carbonyl- 11 C]WAY-100635 and [ 11 C]-(+)-PHNO were prepared with high reliability and satisfying outcome. - Highlights: • Generalized method for in-loop 11 C-carboxylations implemented. • Grignard reactions successfully tested. • First in-loop procedure for [ 11 C]-(+)PHNO established. • Satisfactory synthesis outcome for both [carbonyl- 11 C]WAY-100635 and [ 11 C]-(+)PHNO. • No distillation for purification of intermediate required

  4. Effects of Designer Hyper-Interleukin 11 (H11 on Hematopoiesis in Myelosuppressed Mice.

    Directory of Open Access Journals (Sweden)

    Hanna Dams-Kozlowska

    Full Text Available The incidence of cancer is constantly increasing. Chemo/radiotherapy is one of major methods of treating cancer. Although adverse chemo/radiotherapy events, such as anemia and neutropenia, can be successfully cured, thrombocytopenia is still problematic. We constructed the Hyper-IL11 (H11 cytokine by linking soluble interleukin 11 receptor alpha (sIL-11Ralpha with IL-11. In vivo H11 activity was examined in myelosuppressed mice. Myelosuppression was induced by either i sublethal irradiation and carboplatin administration or ii sublethal irradiation. A dose of 100 μg/kg of H11 or IL-11 was administered subcutaneously for 7 days. IL-11 and H11 accelerated leukocyte, hematocrit and platelet recovery. The effect on the attenuation of thrombocytopenia was significant. Moreover, both cytokines increased the cellularity and numbers of megakaryocyte, erythroid, and granulocyte/macrophage progenitors in the bone morrow and spleen compared with the control. Although H11 was administered at a molar concentration that was three times lower, its effects were comparable with or better than those of IL-11; thus, the activity of H11 was superior to that of IL-11. Because no toxicity was observed after the intravenous administration of H11, this hyper-cytokine may be potentially useful for treatment of thrombocytopenia and other IL-11-dependent disorders.

  5. Labeling of 3H11 With 123I and Its Biodistribution

    International Nuclear Information System (INIS)

    Qin Hongbin; Yin Wei; Gao Huibo; Chen Daming; Qi Benzhong; Jin Xiaohai; Bai Hongsheng; Zhang Wenhui; Yang Zhi

    2010-01-01

    3H11 was labeled with 123 I by Iodogen method,and the labeling product were purified with PD-10 column. The labeling yield and the radiochemical purity of the product was determined by paper chromatography. The biodistribution of 123 I-3H11 in normal mice was car ride out as well. The optimal experimental conditions of 123 I-3H11 was as follow: Iodogen 10 μg, 3H11 30 μg, Na 123 I solution 20 μL (13.3 MBq), PBS 100 μL (pH 7.4, 0.2 mol/L), the normal temperature for 8 min. The labeling yield of 123 I-3H11 was 70%-80%. After stored at 4 degree C for 48 h in human serum,the radiochemical purity was more than 92%. The results of biodistribution showed that the clearance of radiolabeled antibody in blood (half time, T 1/2 ) was 12.25±0.25 h, and the radioactivity in the stomach was up taken obviously. The above results indicated that 123 I-3H11 appears to show some potential as gastric cancer imaging diagnostic agent. (authors)

  6. 1-[(1-Methyl-1H-imidazol-5-ylmethyl]-1H-indole-5-carbonitrile

    Directory of Open Access Journals (Sweden)

    Josephus Jacobus de Jager

    2012-12-01

    Full Text Available In the title compound, C14H12N4, the dihedral angle between the indole ring system (r.m.s. deviation = 0.010 Å and the imidazole ring is 77.70 (6°. In the crystal, molecules are linked by C—H...N hydrogen bonds. One set of hydrogen bonds forms an undulating chain running parallel to the b-axis direction, while the other undulating chain is parallel to the c-axis direction. In combination, (100 sheets result.

  7. Synthesis and evaluation of inhaled [11C]butane and intravenously injected [11C]acetone as potential radiotracers for studying inhalant abuse

    International Nuclear Information System (INIS)

    Gerasimov, Madina R.; Ferrieri, Richard A.; Pareto, Deborah; Logan, Jean; Alexoff, David; Ding Yushin

    2005-01-01

    The phenomenon of inhalant abuse is a growing problem in the US and many countries around the world. Yet, relatively little is known about the pharmacokinetic properties of inhalants that underlie their abuse potential. While the synthesis of 11 C-labeled toluene, acetone and butane has been proposed in the literature, none of these compounds has been developed as radiotracers for PET studies. In the present report we extend our previous studies with [ 11 C]toluene to include [ 11 C]acetone and [ 11 C]butane with the goal of comparing the pharmacokinetic profiles of these three volatile abused substances. Both [ 11 C]toluene and [ 11 C]acetone were administered intravenously and [ 11 C]butane was administered via inhalation to anesthesized baboons. Rapid and efficient uptake of radiolabeled toluene and acetone into the brain was followed by fast clearance in the case of toluene and slower kinetics in the case of acetone. [ 11 C]Butane was detected in the blood and brain following inhalation, but the levels of radioactivity in both tissues dropped to half of the maximal values over the period of less than a minute. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled acetone and butane in nonhuman primates. These data provide insight into the pharmacokinetic features possibly associated with the abuse liability of toluene, acetone and butane

  8. {1-[(3,5-Dimethyl-4H-1,2,4-triazol-4-ylimino]ethyl}ferrocene

    Directory of Open Access Journals (Sweden)

    Mao-Ping Song

    2008-10-01

    Full Text Available In the title compound, [Fe(C5H5(C11H13N4], the triazolyl and Cp ring form a dihedral angle of 76.6 (3°. In the crystal structure, there are both intra- and intermolecular C—H...π interactions, forming a one-dimensional chain structure along [010].

  9. (Acetonitrile-κNchloridobis[2-(pyridin-2-ylphenyl-κ2C1,N]iridium(III

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    Florian Blasberg

    2011-12-01

    Full Text Available The IrIII atom of the title compound, [Ir(C11H8N2Cl(CH3CN], displays a distorted octahedral coordination. The pyridyl groups are in trans positions [N—Ir—N = 173.07 (10°], while the phenyl groups are trans with respect to the acetonitrile and chloride groups [C—Ir—N = 178.13 (11 and C—Ir—Cl = 176.22 (9°]. The pyridylphenyl groups only show a small deviation from planarity, with the dihedral angle between the planes of the two six-membered rings in each pyridylphenyl group being 5.6 (2 and 5.8 (1°. The crystal packing shows intermolecular C—H...Cl, C—H...π(acetonitrile and C—H...π(pyridylphenyl contacts.

  10. Synthesis of O-[{sup 11}C]acetyl CoA, O-[{sup 11}C]acetyl-L-carnitine, and L-[{sup 11}C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

    1997-07-01

    The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with {sup 11}C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1-{sup 11}C]acetyl CoA and O-[2-{sup 11}C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1-{sup 11}C]acetyl-L-carnitine and O-[2-{sup 11}C]acetyl-L-carnitine in 70-80% yield, based on [1-{sup 11}C]acetate or [2-{sup 11}C]acetate, respectively. By an N-methylation reaction with [{sup 11}C]methyl iodide, L-[methyl-{sup 11}C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl-{sup 11}C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [{sup 11}C]methyl iodide. Initial data of the kinetics of the different {sup 11}C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented.

  11. 10-(Prop-2-ynyl-10H-phenothiazine

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    Younas Aouine

    2010-11-01

    Full Text Available In the molecule of the title compound, C15H11NS, the butterfly angle between the two planes defined by the two wings of the phenothiazine unit is 33.5 (8°. The dihedral angles between the two benzene rings and the propynyl group are 85 (4 and 63 (4°.

  12. Assessment of cerebral P-glycoprotein expression and function with PET by combined [11C]inhibitor and [11C]substrate scans in rats

    International Nuclear Information System (INIS)

    Müllauer, Julia; Karch, Rudolf; Bankstahl, Jens P.; Bankstahl, Marion; Stanek, Johann; Wanek, Thomas; Mairinger, Severin; Müller, Markus; Löscher, Wolfgang; Langer, Oliver; Kuntner, Claudia

    2013-01-01

    Introduction: The adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (Pgp) protects the brain from accumulation of lipophilic compounds by active efflux transport across the blood–brain barrier. Changes in Pgp function/expression may occur in neurological disorders, such as epilepsy, Alzheimer’s or Parkinson’s disease. In this work we investigated the suitability of the radiolabeled Pgp inhibitors [ 11 C]elacridar and [ 11 C]tariquidar to visualize Pgp density in rat brain with PET. Methods: Rats underwent a first PET scan with [ 11 C]elacridar (n = 5) or [ 11 C]tariquidar (n = 6) followed by a second scan with the Pgp substrate (R)-[ 11 C]verapamil after administration of unlabeled tariquidar at a dose which half-maximally inhibits cerebral Pgp (3 mg/kg). Compartmental modeling using an arterial input function and Logan graphical analysis were used to estimate rate constants and volumes of distribution (V T ) of radiotracers in different brain regions. Results: Brain PET signals of [ 11 C]elacridar and [ 11 C]tariquidar were very low (∼ 0.5 standardized uptake value, SUV). There was a significant negative correlation between V T and K 1 (i.e. influx rate constant from plasma into brain) values of [ 11 C]elacridar or [ 11 C]tariquidar and V T and K 1 values of (R)-[ 11 C]verapamil in different brain regions which was consistent with binding of [ 11 C]inhibitors to Pgp and efflux of (R)-[ 11 C]verapamil by Pgp. Conclusion: The small Pgp binding signals obtained with [ 11 C]elacridar and [ 11 C]tariquidar limit the applicability of these tracers to measure cerebral Pgp density. PET tracers with higher (i.e. subnanomolar) binding affinities will be needed to visualize the low density of Pgp in brain

  13. Radiosynthesis and in vitro evaluation of 2-(N-alkyl-N-1'-11C-propyl)amino-5-hydroxytetralin analogs as high affinity agonists for dopamine D-2 receptors

    International Nuclear Information System (INIS)

    Shi Bingzhi; Narayanan, Tanjore K.; Yang, Z.-Y.; Christian, Bradley T.; Mukherjee, Jogeshwar

    1999-01-01

    We have developed radiotracers based on agonists that may potentially allow the in vivo assessment of the high affinity (HA) state of the dopamine D-2 receptors. The population of HA state, which is likely the functional state of the receptor, may be altered in certain diseases. We carried out radiosyntheses and evaluated the binding affinities, lipophilicity, and in vitro autoradiographic binding characteristics of three dopamine D-2 receptor agonists: (±)-2-(N,N-dipropyl)amino-5-hydroxytetralin (5-OH-DPAT), (±)-2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT), and (±)-2-(N-cyclohexylethyl-N-propyl)amino-5-hydroxytetralin (ZYY-339). In 3 H-spiperone assays using rat striata, ZYY-339 exhibited subnanomolar affinity for D-2 receptor sites ( IC 50 =0.010 nM), PPHT was somewhat weaker ( IC 50 =0.65 nM), and 5-OH-DPAT exhibited the weakest affinity ( IC 50 =2.5 nM) of the three compounds. Radiosynthesis of these derivatives, 2-(N-propyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-5-OH-DPAT), 2-(N-phenethyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-PPHT), and 2-(N-cyclohexylethyl-N-1'- 11 C-propyl)amino-5-hydroxytetralin ( 11 C-ZYY-339) was achieved by first synthesizing 11 C-1-propionyl chloride and subsequent coupling with the appropriate secondary amine precursor to form the respective amide, which was then reduced to provide the desired tertiary amine products. The final products were obtained by reverse-phase high performance liquid chromatography (HPLC) purification in radiochemical yields of 5-10% after 60-75 min from the end of 11 CO 2 trapping and with specific activities in the range of 250-1,000 Ci/mmol. In vitro autoradiographs in rat brain slices with 11 C-5-OH-DPAT, 11 C-PPHT, and 11 C-ZYY-339 revealed selective binding of the three radiotracers to the dopamine D-2 receptors in the striata

  14. Evaluation of [O-methyl-11C]RS-15385-197 as a positron emission tomography radioligand for central α2-adrenoceptors

    International Nuclear Information System (INIS)

    Hume, S.P.; Hirani, E.; Opacka-Juffry, J.; Osman, S.; Myers, R.; Gunn, R.N.; McCarron, J.A.; Pike, V.W.; Clark, R.D.; Melichar, J.; Nutt, D.J.

    2000-01-01

    Carbon-11 labelled RS-15385-197 and its ethylsulphonyl analogue, RS-79948-197, were evaluated in rats as potential radioligands to image central α 2 -adrenoceptors in vivo. The biodistributions of both compounds were comparable with that obtained in an earlier study using tritiated RS-79948-197 and were consistent with the known localisation of α 2 -adrenoceptors. The maximal signals (total to non-specific binding) were, however, reduced, in the order [ 11 C]RS-79948-197 11 C]RS-15385-197 3 H]RS-79948-197, primarily due to the difference in radiolabel position (O-methyl for carbon-11 compared with S-ethyl for tritium). This resulted in the in-growth of radiolabelled metabolites in plasma, which, in turn, contributed to the non-specific component of brain radioactivity. Nonetheless, the signal ratio of ∝5 for a receptor-dense tissue compared with the receptor-sparse cerebellum, at 90-120 min after radioligand injection, encouraged the development of [O-methyl- 11 C]RS-15385-197 for human positron emission tomography (PET). Unfortunately, in two human PET scans (each of 90 min), brain extraction of the radioligand was minimal, with volumes of distribution more than an order of magnitude lower than that measured in rats. Following intravenous injection, radioactivity was retained in plasma and metabolism of the radiolabelled compound was very low. Retrospective measurements of in vitro plasma protein binding and in vivo brain uptake index (BUI) in rats demonstrated a higher protein binding of the radioligand in human compared with rat plasma and a lower BUI in the presence of human plasma. It is feasible that a higher affinity of RS-15385-197 for human plasma protein compared with receptor limited the transport of the radioligand. Although one of the PET scans showed a slight heterogeneity in biodistribution of radioactivity which was consistent with the known localisation of α 2 -adrenoceptors in human brain, it was concluded that [O-methyl- 11 C]RS-15385

  15. Crystal structure of 4-aminobenzoic acid–4-methylpyridine (1/1

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    M. Krishna Kumar

    2015-02-01

    Full Text Available In the title 1:1 adduct, C6H7N·C7H7NO2, the carboxylic acid group is twisted at an angle of 4.32 (18° with respect to the attached benzene ring. In the crystal, the carboxylic acid group is linked to the pyridine ring by an O—H...N hydrogen bond, forming a dimer. The dimers are linked by N—H...O hydrogen bonds, generating (010 sheets.

  16. (+-Chlorido[(1,2,3,4-η;κP2′-2′-diphenylphosphanyl-2-diphenylphosphoryl-1,1′-binaphthyl]rhodium(I methanol monosolvate

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    Hans-Joachim Drexler

    2012-03-01

    Full Text Available In the title complex, [RhCl(C44H32OP2]·CH3OH, the RhI ion is coordinated by a naphthyl group of a partially oxidized 2,2′-bis(diphenylphosphanyl-1,1′-binaphthyl (BINAP ligand in a η4 mode, one P atom of the diphenylphosphanyl group and one Cl atom. The P=O group does not interact with the RhI ion but accepts an O—H...O hydrogen bond from the methanol solvent molecule.

  17. 4-[(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-ylphenylmethyl]-5-methyl-2-phenyl-1H-pyrazol-3(2H-one ethanol hemisolvate

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2009-01-01

    Full Text Available The asymmetric unit of the title compound, C27H24N4O2·0.5C2H6O, comprises two crystallographically independent molecules (A and B with slightly different conformations, and one ethanol molecule of crystallization. Intramolecular C—H...O and O—H...O hydrogen bonds generate six- and eight-membered rings, producing S(6 and S(8 ring motifs, respectively. In molecule A, one of the benzene rings is disordered over two positions, with site-occupancy factors of 0.542 (11 and 0.458 (11. The dihedral angles between the central benzene ring and the two outer benzene rings are 73.88 (9 and 82.6 (2/88.9 (2° in molecule A, and 80.81 (8 and 79.38 (8° in molecule B. In the crystal structure, molecules form infinite one-dimensional chains in the (101 plane. The crystal structure is stabilized by intermolecular O—H...N, N—H...N, N—H...O and C—H...O hydrogen bonds, weak C—H...π and π–π [centroid–centroid = 3.5496 (1 Å] interactions.

  18. The 12C(n, 2n)11C cross section from threshold to 26.5 MeV.

    Science.gov (United States)

    Yuly, M; Eckert, T; Hartshaw, G; Padalino, S J; Polsin, D N; Russ, M; Simone, A T; Brune, C R; Massey, T N; Parker, C E; Fitzgerald, R; Sangster, T C; Regan, S P

    2018-02-01

    The 12 C(n, 2n) 11 C cross section was measured from just below threshold to 26.5 MeV using the Pelletron accelerator at Ohio University. Monoenergetic neutrons, produced via the 3 H(d,n) 4 He reaction, were allowed to strike targets of polyethylene and graphite. Activation of both targets was measured by counting positron annihilations resulting from the β + decay of 11 C. Annihilation gamma rays were detected, both in coincidence and singly, using back-to-back NaI detectors. The incident neutron flux was determined indirectly via 1 H(n,p) protons elastically scattered from the polyethylene target. Previous measurements fall into upper and lower bands; the results of the present measurement are consistent with the upper band.

  19. Conversion of no-carrier-added [11C]carbon dioxide to [11C]carbon monoxide on molybdenum for the synthesis of 11C-labelled aromatic ketones

    International Nuclear Information System (INIS)

    Zeisler, S.K.; Nader, M.; Theobald, A.; Oberdorfer, F.

    1997-01-01

    A new method for the efficient conversion of no-carrier-added [ 11 C]carbon dioxide into [ 11 C]carbon monoxide is described. [ 11 C]Carbon dioxide produced by proton bombardment of ultra high purity nitrogen is pre-concentrated in a cryo trap and then passed through a quartz tube filled with a mesh of thin molybdenum wire heated to 850 o C. [ 11 C]Carbon dioxide readily reacts with molybdenum to form [ 11 C]carbon monoxide and molybdenum(IV) oxide. The latter also reduces carbon dioxide to carbon monoxide and helps improve the performance of the converter. [ 11 C]Carbon monoxide is purified from remaining [ 11 C]carbon dioxide and collected in a small silica trap from which it is eluted into a reaction mixture for the palladium-mediated synthesis of a 11 C-labelled aromatic ketone. Radiochemical yields of up to 81% (decay-corrected) for [ 11 C]carbon monoxide were obtained. Radiochemical purity and specific radioactivity of both [ 11 C]carbon monoxide and the 11 C-labelled ketone are sufficient for nuclear medical studies with PET. (Author)

  20. N-(2-Methylphenyl-1,2-benzoselenazol-3(2H-one

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    Xu Zhu

    2013-10-01

    Full Text Available In the title Ebselen [systematic name: (2-phenyl-1,2-benzoisoselenazol-3-(2H-one] analogue, C14H11NOSe, the benzisoselenazolyl moiety (r.m.s. deviation = 0.0209 Å is nearly perpendicular to the N-arenyl ring, making a dihedral angle of 78.15 (11°. In the crystal, molecules are linked by C—H...O and Se...O interactions into chains along the c-axis direction. The Se...O distance [2.733 (3 Å] is longer than that in Ebselen (2.571 (3 Å].

  1. (Benzyl isocyanide-κC1chlorido(2-chloro-3-dimethylamino-1-phenylprop-1-en-1-yl-κ2C1,Npalladium(II

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    Ana C. Mafud

    2013-01-01

    Full Text Available In the title compound, [Pd(C11H13ClNCl(C8H7N], which crystallized in the chiral space group P212121, the PdII atom is coordinated by two C atoms, a Csp2 atom of the 2-chloro-3-dimethylamino-1-phenylprop-1-en-1-yl ligand and a Csp atom from the benzyl isocyanide ligand, as well as an N atom of the ligand and a Cl atom, in a square-planar geometry. In the complex, there is a short C—H...Cl hydrogen bond and a C—H...π interaction. In the crystal, molecules are linked via C—H...Cl hydrogen bonds, forming chains along the a-axis direction.

  2. 1-[(1R,2S,4R,7S-3,3-Dichloro-4,11,11-trimethyltricyclo[5.4.0.02,4]undecan-7-yl]ethanone

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    Ahmed Benharref

    2017-02-01

    Full Text Available The title compound, C16H24Cl2O, crystallizes with two independent molecules in the asymmetric unit. Each molecule is built up from two fused six-membered rings, one of which is fused to a three-membered ring. The two molecules differ essentially in the orientation of two of the methyl groups. The dihedral angles between the mean planes through the two six-membered rings are 57.98 (13 and 55.29 (13°. The molecular conformation is stabilized by intramolecular C—H...Cl hydrogen bonds.

  3. 1-[5-(2-Chlorophenyl-3-(4-methylphenyl-4,5-dihydro-1H-pyrazol-1-yl]ethan-1-one

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    Farook Adam

    2016-01-01

    Full Text Available The title compound, C18H17ClN2O, crystallized with two independent molecules (the S and R enantiomers in the asymmetric unit. The molecules are V-shaped with the two aromatic rings inclined to one another by 78.78 (11 and 81.23 (11°. In the crystal, molecules are linked via C—H...O hydrogen bonds, forming chains along the c-axis direction. The chains are linked via C—H...π interactions, forming a three-dimensional framework. The crystal structure was refined as a two-component twin.

  4. Tracers development for the PET study of nicotinic receptors: [{sup 11}C]-mecamylamine and [{sup 11}C]-SIB 1553A. Tritium and carbon-11 radiolabelling of a serine proteinase inhibitor: the t-PA{sub stop}; Developpement de traceurs pour l'etude des recepteurs nicotiniques par TEP: la [{sup 11}C]-mecamylamine et le [{sup 11}C]SIB 1553A. Radiomarquages par le tritium et le carbone-11 d'un inhibiteur d'une serine protease: le t-PA{sub stop}

    Energy Technology Data Exchange (ETDEWEB)

    Sobrio, F.

    2002-12-15

    In order to develop radiotracers for the Positron Emission Tomography (PET), we labelled both the mecamylamine and SIB-1553A with carbon-11 to study the nicotinic cholinergic receptors (nAChRs). The radiosynthesis of [{sup 11}C]-t-PA{sub stop} and the labelling with tritium of one analogue were realized for cerebral ischemia PET studies. The [{sup 11}C]-mecamylamine, a non-competitive and non-selective nAChRs antagonist was synthesized in 45 min via a N-[{sup 11}C]-methylation reaction. In the rat brain, the ex vivo studies showed no radio-metabolite 45 min after the injection of [{sup 11}C]-mecamylamine. The uptake kinetics in the rat brain or in vivo by PET in the anesthetized baboon or in the conscious monkey, reached a plateau around 45-50 min after injection. However, the saturation or displacement experiments did not permit to exhibit nor a significant difference of labelling between the different cerebral regions nor a specific uptake. In consequence, the [{sup 11}C]-mecamylamine was not an appropriate radioligand for nAChRs PET study. The labelling of [{sup 11}C]-SIB 1553A, a selective agonist for the nicotinic {beta}4 subunit, required the synthesis in 5 steps (56% overall yield) of precursor for the incorporation of carbon-11. The radiosynthesis was performed in 36 min by a N-[{sup 11}C]-methylation reaction (yield: 75%). The [{sup 11}C]-t-PA{sub stop} was obtained from [{sup 11}C]-KCN with yields from 80 to 90%. For the first time with carbon-11, the formation of an amidine group was realized from a nitrile group. The labelling by isotopic exchange of hydrogen by tritium of the t-PA{sub stop} did not permit to obtain the [{sup 3}H]-t-PA{sub stop} but a tritiated analogue. This compound will be used to study its vectorization by micro-encapsulation. (author)

  5. Crystal structure of ethyl (2S-9-methoxy-2-methyl-4-oxo-3,4,5,6-tetrahydro-2H- 2,6-methanobenzo[g][1,3,5]oxadiazocine-11-carboxylate

    Directory of Open Access Journals (Sweden)

    A. Dhandapani

    2015-02-01

    Full Text Available In the title compound, C15H18N2O5, the methoxyphenyl ring makes a dihedral angle of 84.70 (12° with the mean plane of the tetrahydropyrimidin-2(1H-one ring. Both the pyran and tetrahydropyrimidin-2(1H-one rings have distorted envelope conformations with the carboxylate-substituted C atom as the flap. In the crystal, molecules are linked via pairs of N—H...O hydrogen bonds, forming zigzag chains propagating along [010], which enclose R22(8 ring motifs. The chains are linked by C—H...π interactions, forming a two-dimensional network parallel to (100.

  6. Crystal structure of 4,4′-bis[3-(piperidin-1-ylprop-1-yn-1-yl]-1,1′-biphenyl

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    Anqi Walbaum

    2017-06-01

    Full Text Available The title compound, C28H32N2, (I, is one of a second generation of compounds designed and synthesized based on a very potent and selective α9α10 nicotinic acetylcholine receptor antagonist ZZ161C {1,1′-[[1,1′-biphenyl]-4,4′-diylbis(prop-2-yne-3,1-diyl]bis(3,4-dimethylpyridin-1-ium bromide}, which has shown analgesic effects in a chemotherapy-induced neuropathy animal model. Compound (I was synthesized by the reaction of 4,4′-bis(3-bromoprop-1-yn-1-yl-1,1′-biphenyl with piperidine at room temperature in acetonitrile. The single-crystal used for X-ray analysis was obtained by dissolving (I in a mixture of dichloromethane and methanol, followed by slow evaporation of the solvent. In the crystal of (I, the biphenyl moiety has a twisted conformation, with a dihedral angle of 25.93 (4° between the benzene rings. Both piperidine head groups in (I are in the chair conformation and are oriented so that the N-atom lone pairs of each piperidine group point away from the central biphenyl moiety.

  7. 3-(4-Fluorophenyl-1-[1′-(4-fluorophenyl-2-oxo-5′,6′,7′,7a′-tetrahydro-1H-indole-3(2H-spiro-3′(2H-1H′-pyrrolizin-2′-yl]prop-2-en-1-one

    Directory of Open Access Journals (Sweden)

    S. Sriman Narayanan

    2008-09-01

    Full Text Available In the title compound, C29H24F2N2O2, one of the pyrrolidine rings of the pyrrolizine system is disordered over two sites, with occupancy factors 0.734:0.266 (12. Both components of the disordered pyrrolidine ring adopt envelope conformations, whereas the other pyrrolidine ring adopts a twist conformation. The molecules are linked into centrosymmetric dimers by N—H...O hydrogen bonds and the dimers are connected via C—H...π interactions. The crystal structure is also stabilized by intermolecular C—H...F hydrogen bonds.

  8. Triphenyl{(E-4-[4-(phenyldiazenylphenyl]-4H-1,2,4-triazol-1-yl}boron

    Directory of Open Access Journals (Sweden)

    Daisuke Urakami

    2009-10-01

    Full Text Available In the title compound, C32H26BN5 or [(C14H11N5B(C6H53], the B atom is approximately tetrahedrally coordinated. The diazo unit is in a trans conformation, which is generally more stable than a cis one for aromatic azo compounds. The crystal structure features very weak C—H...π interactions. The dihedral angles between the central benzene ring and the terminal rings in the heterocycle are 62.64, 73.54 and 61.60°.

  9. Carbon-11 labelling of an inhibitor of acetylcholinesterase: [11C]physostigmine

    International Nuclear Information System (INIS)

    Bonnot-Lours, S.; Crouzel, C.; Prenant, C.; Hinnen, F.

    1993-01-01

    Physostigmine, an alkaloid from calabar bean is a strong inhibitor of acetylcholinesterase and has been used clinically in the treatment of glaucoma, atropine intoxication, myasthenia gravis and more recently, in experimental trials in Alzheimer's disease. In order to study the AChE activity in the brain by positron emission tomography, we have undertaken the labelling of physostigmine with carbon-11. The synthesis involves the reaction of [ 11 C]methylisocyanate with eseroline. [ 11 C]Methylisocyanate was obtained by heating [ 11 C]acetylchloride with tetrabutylammonium azide in toluene. The synthesis of [ 11 C]CH 3 COC1 involves the carbonation of methylmagnesium bromide in THF with cyclotron produced [ 11 C]carbon dioxide and the addition of phthaloyl dichloride. The [ 11 C]methylisocyanate is distilled into a solution of eseroline in ether with a small piece of sodium. After 10 minutes at 25 o C, the solution is purified by HPLC and the appropriate fraction collected. Starting with 55.5 GBq (1.5 Ci) of [ 11 C]carbon dioxide, 0.92-1.48 GBq (25-40 mCi) of [ 11 C]Physostigmine are obtained 57 minutes after EOB. (author)

  10. Methyl (9aR*,10S*,11R*,13aS*,13bS*-9-oxo-6,7,9,9a,10,11-hexahydro-5H,13bH-11,13a-epoxypyrrolo[2′,1′:3,4][1,4]diazepino[2,1-a]isoindole-10-carboxylate

    Directory of Open Access Journals (Sweden)

    Flavien A. A. Toze

    2011-11-01

    Full Text Available The title compound, C17H18N2O4, is the methyl ester of the adduct of intramolecular Diels–Alder reaction between maleic anhydride and 1-(2-furyl-2,3,4,5-tetrahydro-1H-pyrrolo[1,2-a][1,4]diazepine. The molecule comprises a fused pentacyclic system containing four five-membered rings (viz. pyrrole, 2-pyrrolidinone, tetrahydrofuran and dihydrofuran and one seven-membered ring (1,4-diazepane. The pyrrole ring is approximately planar (r.m.s. deviation = 0.003 Å while the 2-pyrrolidinone, tetrahydrofuran and dihydrofuran five-membered rings have the usual envelope conformations. The central seven-membered diazepane ring adopts a boat conformation. In the crystal, molecules are bound by weak intermolecular C—H...O hydrogen-bonding interactions into zigzag chains propagating in [010]. In the crystal packing, the chains are stacked along the a axis.

  11. 11-[Bis(trimethylsilylamino]-2,4-bis(trimethylsilyl-7,8,9,10-tetrahydro-6H-cyclohepta[1,2-b]quinoline

    Directory of Open Access Journals (Sweden)

    Ísmail Çelik

    2017-06-01

    Full Text Available In the title compound, C26H48N2Si4, the cycloheptane ring adopts a chair conformation, while the quinolinyl ring system is almost planar [maximum deviation = 0.040 (3 Å for one of the C atoms carrying a Me3Si group]. In the crystal, in the absence of classical hydrogen bonding, the packing is dominated by van der Waals forces. One of the N-bound trimethylsilyl groups is disordered by rotation about the C—SiMe3 bond, and was modelled over two sets of sites in the ratio 0.873 (8:0.127 (8.

  12. Modified synthesis of 11-[14C]-clozapine

    International Nuclear Information System (INIS)

    Matloubi, Hojatollah; Ghandi, Mehdi; Zarrindast, M.-R.; Saemian, Nader

    2001-01-01

    The reported synthetic pathway of 8-chloro-11-(4-methyl-1-piperazinyl)-11-[ 14 C]-5H-dibenzo[b,e][1,4]diazapine (clozapine) was modified in several steps. The synthetic pathway was shortened by 60% and the total yield was increased from 6% to 23%

  13. MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.

    Science.gov (United States)

    Posavec Marjanović, Melanija; Hurtado-Bagès, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Hélène; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M; Ahel, Ivan; Ladurner, Andreas G; Yanes, Oscar; Bouvet, Philippe; Suelves, Mònica; Teperino, Raffaele; Pospisilik, J Andrew; Buschbeck, Marcus

    2017-11-01

    Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD + -derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD + consumption. The resultant accumulation of the NAD + precursor NMN allows for maintenance of mitochondrial NAD + pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD + consumption and establishing a buffer of NAD + precursors in differentiated cells.

  14. Automated radiochemical synthesis and biodistribution of [11C]l-α-acetylmethadol ([11C]LAAM)

    International Nuclear Information System (INIS)

    Sai, Kiran Kumar Solingapuram; Fan, Jinda; Tu, Zhude; Zerkel, Patrick; Mach, Robert H.; Kharasch, Evan D.

    2014-01-01

    Long-acting opioid agonists methadone and l-α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [ 11 C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharmacologic similarities, we aimed to develop [ 11 C]LAAM as a PET ligand to probe the brain exposure of long-lasting opioids in humans. This manuscript describes [ 11 C]LAAM synthesis and its biodistribution in mice. The radiochemical synthetic strategy afforded high radiochemical yield, purity and specific activity, thereby making the synthesis adaptable to automated modules. - Highlights: • Radiochemical synthesis of opioid [ 11 C]l-α-acetylmethadol (LAAM) described for the first time. • High radiochemical yield, purity and specific activity. • Easily reproducible and adaptable synthesis to any C-11 automated modules. • [ 11 C]LAAM utility as a PET radiopharmaceutical for assessing brain penetration

  15. Synthesis of 9H-Indeno [1, 2-b] Pyrazine and 11H-Indeno [1, 2-b ...

    African Journals Online (AJOL)

    NICO

    Synthesis of 9H-Indeno [1, 2-b] Pyrazine and. 11H-Indeno [1, 2-b] Quinoxaline Derivatives in. One-step Reaction from 2-Bromo-4-chloro-1-indanone. S. Jasouri1,2, J. Khalafy1,*, M. Badali2 and R.H. Prager3. 1Department of Chemistry, Urmia University, Urmia 57154, Iran. 2Daana Pharmaceutical Co., P.O. Box 5181, Tabriz ...

  16. Evidence and detailed study of a second-order phase transition in the (C6H11NH3)2[PbI4] organic-inorganic hybrid material

    International Nuclear Information System (INIS)

    Yangui, A.; Pillet, S.; Garrot, D.; Boukheddaden, K.; Triki, S.; Abid, Y.

    2015-01-01

    The thermal properties of the organic-inorganic hybrid material (C 6 H 11 NH 3 ) 2 [PbI 4 ] are investigated using diffuse reflectivity, spectroscopic ellipsometry, differential scanning calorimetry, Raman spectroscopy, and X-ray diffraction. The diffuse reflectivity, performed in heating mode, clearly evidences the presence of a singularity at 336 K. This is confirmed by the temperature dependence of the spectroscopic ellipsometry spectra, which points out a second-order phase transition at 336 K with a critical exponent ∼0.5. Differential scanning calorimetry measurements on a polycrystalline powder of (C 6 H 11 NH 3 ) 2 [PbI 4 ] show a reversible phase transition detected at T C  = 336 K without hysteresis. Raman spectroscopy data suggest that this transition arises from a change in the interactions between inorganic sheets (([PbI 4 ] 2− ) ∞ ) and organic protonated molecules ([C 6 H 11 NH 3 ] + ). The structural analysis from power X-ray diffraction reveals an incomplete order-disorder transition of the cyclohexylammonium cation, causing a subtle contraction of the inter-plane distance. The transition results from repulsive close contacts between the organic molecules in the interlayer spacing

  17. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H., E-mail: shapirob@vet.upenn.edu

    2015-04-01

    Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2

  18. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    International Nuclear Information System (INIS)

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H.

    2015-01-01

    Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2

  19. Synthesis, characterization, electrochemical investigation and antioxidant activities of a new hybrid cyclohexaphosphate: Cu1.5Li(C2H10N2)P6O18·7H2O

    Science.gov (United States)

    Sleymi, Samira; Lahbib, Karima; Rahmouni, Nihed; Rzaigui, Mohamed; Besbes-Hentati, Salma; Abid, Sonia

    2017-09-01

    A new organic-inorganic hybrid transition metal phosphate, Cu1.5Li(C2H10N2)P6O18·7H2O, has been prepared and characterized by X-ray diffraction, spectroscopy (infrared, Raman, diffuse reflectance and UV-Vis) and thermal analysis (TG). In addition, its electrochemical behaviors, as well as its antioxidant and antibacterial activities, have been investigated. Its structure is built up by the alternate linkages between copper and phosphate polyhedra, forming puckered layers with intersecting 12-membered rings, in which the ethylenediammonium cations reside. This compound is the first framework structure constructed from cyclohexaphosphates and three distinct copper cations. Cyclic voltammetry study in an acetonitrile solution reveals the facile anodic oxidation of its organic part on a platinum disk and a progressive growing of a thin film, though the repetitive cycling of potential. The title compound was tested for its in vitro antioxidant activities by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2‧-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Ferrous chelating ability (FIC) and Ferric Reducing Power (FRP) methods. The antioxidant activity of Cu1.5Li(C2H10N2)P6O18·7H2O was analyzed simultaneously with its antibacterial capacity against Escherichia coli, Salmonella typhimurium, Staphylococus aureus, Enterococcus feacium, Streptococcus agalactiae and Candida albicans. The tested compound showed significant antioxidant activities with low antibacterial properties.

  20. Sandwich iridium complexes with the monoanionic carborane ligand [9-SMe2-7,8-C2B9H10]-

    International Nuclear Information System (INIS)

    Loginov, D.A.; Vinogradov, M.M.; Perekalin, D.S.; Starikova, Z.A.; Lysenko, K.A.; Petrovskij, P.V.; Kudinov, A.R.

    2006-01-01

    The reaction of the [(η-9-SMe 2 -7,8-C 2 B 9 H 10 )IrBr 2 ] 2 complex with Tl[Tl(η-7,8-C 2 B 9 H 11 )] afforded the iridacarborane compound (η-9-SMe 2 -7,8-C 2 B 9 H 10 )Ir(η-7,8-C 2 B 9 H 11 ). The cationic complex [Cp*Ir(η-9-SMe 2 -7,8-C 2 B 9 H 10 )] + PF 6 - (Cp* is pentamethylcyclopentadienyl) was synthesized by the reaction of [Cp*IrCl 2 ] 2 with Na[9-SMe 2 -7,8-C 2 B 9 H 10 ]. The structures of (η-9-SMe 2 -7,8-C 2 B 9 H 10 )Ir(η-cod) (cod is 1,5-cyclooctadiene) and [Cp*Ir(η-9-SMe 2 -7,8-C 2 B 9 H 10 ]PF 6 were established by X-ray diffraction [ru

  1. New Approaches for the Synthesis, Cytotoxicity and Toxicity of Heterocyclic Compounds Derived from 2-Cyanomethylbenzo[c]imidazole.

    Science.gov (United States)

    Mohareb, Rafat M; Mohamed, Abeer A; Abdallah, Amira E M

    2016-01-01

    The reaction of ethyl cyanoacetate with o-phenylenediamine gave the 2-cyanomethylbenzo[c]imidazole (1). The latter compound was used as the key starting material to synthesise biologically active heterocyclic derivatives. Thus, the reaction of 1 with cyclohexanone and either of benzaldehyde, 4-methoxybenzaldehyde or 4-chlorobenzaldehyde gave the annulated derivatives 2a-c, respectively. The antitumor evaluations of the newly synthesized products against the three cancer cell lines MCF-7 (breast adeno-carcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) showed that compounds 2b, 6, 11b, 11c, 12b, 16a, 16b and 18a exhibited optimal cytotoxic effect against cancer cell lines, with IC50 values in the nM range. Bioactive compounds are often toxic to shrimp larvae. Thus, in order to monitor these chemicals in vivo lethality to shrimp larvae (Artemia salina), Brine-Shrimp Lethality Assay was used. Compounds 11b, 12b and 16b showed no toxicity against the tested organisms.

  2. Subcellullar localization of tumor-associated antigen 3H11Ag

    International Nuclear Information System (INIS)

    Guo Jianhui; Jin Genglin; Meng Lin; Ma Hong; Nie Dezhi; Wu Jian; Yuan Lan; Shou Chengchao

    2004-01-01

    3H11Ag, a tumor-associated antigen defined by the monoclonal antibody 3H11 that specifically recognizes cancer cells in various tumor tissues, was successfully cloned recently, but its function is unknown. To explore the potential roles it plays in tumors, we analyzed its subcellular localization in the present study. By expressing 3H11Ag fused with fluorescent protein in COS-7 cells, we found that 3H11Ag localizes to both cytoplasm and nucleus, which was confirmed by subcellular fractionation. And sequentially extracting the nuclei of COS-7 cells transfected with 3H11Ag showed that it is a DNA- and nuclear matrix-associated protein. Moreover, by expressing a series of red fluorescent protein-tagged truncated forms of 3H11Ag, it was demonstrated that the 150 amino acid residues at its C-terminal are fully responsible for the subcellular localization. In addition, the results of the computational analysis of 3H11Ag were in accordance with those of the experimental analysis. All these data would be helpful to elucidate the functions of 3H11Ag

  3. Propyl 3-oxo-2,3-dihydro-1,2-benzothia-zole-2-carboxyl-ate.

    Science.gov (United States)

    Wang, Xiang-Hui; Yang, Jian-Xin; You, Cheng-Hang; Lin, Qiang

    2011-09-01

    The title compound, C(11)H(11)NO(3)S, was synthesized by the reaction of benzo[d]isothia-zol-3(2H)-one with propyl carbono-chloridate in toluene. The benzoisothiazolone ring system is approximately planar with a maximum deviation from the mean plane of 0.0226 (14) Å for the N atom. Weak inter-molecular C-H⋯O hydrogen bonding occurs in the crystal structure.

  4. [11C] Methionine as PET radiopharmaceutical produced at CDTN/CNEN

    International Nuclear Information System (INIS)

    Silveira, Marina B.; Ferreira, Soraya Z.; Carvalho, Tiago F.; Silva, Juliana B. da

    2013-01-01

    Carbon-11 ( 11 C) is an attractive radionuclide used in positron emission tomography (PET) since carbon is a ubiquitous element in biomolecules. Positron emitter-labeled amino acids are being widely used as indicators of tumor activity due to enhanced expression of amino acid transporter systems in cancer cells. L-[Methyl-( 11 C)] Methionine or [ 11 C]Methionine is being used in neuro-oncology and, unlike 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 FDG), gives more contrast images and improves brain tumor diagnosis. The aim of this work was to develop the synthesis and quality control of [ 11 C]Methionine at the Radiopharmaceuticals Research and Production Facility (UPPR) of CDTN/CNEN. The synthesis of [ 11 C] Methionine was performed using two Sep-Pak tC18 plus cartridges one as solid support for the 11 C-methylation of the precursor L-homocysteine thiolactone hydrochloride and another for purification. The pH, radionuclidic identity and purity, residual solvents, radiochemical and chemical purity of the final product were evaluated as described on the European Pharmacopoeia 7.0 monograph. Total synthesis time was 18 minutes, the radiochemical yield was approximately 15% (non-decay corrected) and radiochemical purity was greater than 95%. [ 11 C]Methionine was successfully synthesized at CDTN using the described procedures and complied with quality requirements. Due to the rapid growth of oncologic PET scans in last decade, 11 C labelling holds great promises in the next few years with the application of other tracers beyond 18 FDG. This pioneering work of UPPR/CDTN represents a response to the demands of a growing nuclear medicine in the country focused on achieving better diagnostic imaging. (author)

  5. Evaluation of in vivo selective binding of [{sup 11}C]doxepin to histamine H{sub 1} receptors in five animal species

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi E-mail: ishiwata@pet.tmig.or.jp; Kawamura, Kazunori; Wang Weifang; Tsukada, Hideo; Harada, Norihiro; Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Iwata, Ren; Yanai, Kazuhiko

    2004-05-01

    The specific binding of [{sup 11}C]doxepin, which has been used as a radioligand for mapping histamine H{sub 1} receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [{sup 11}C]doxepin uptake was reduced by treatment with cold doxepin and two H{sub 1} receptor antagonists, but not with H{sub 2}/H{sub 3} antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H{sub 1} antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig.

  6. Synthesis of[11C]LY186126, an inhibitor of phosphodiesterase

    International Nuclear Information System (INIS)

    Prenant, C.; Crouzel, C.; Comar, D.; Robertson, D.W.

    1992-01-01

    LY186126 [1,3-dihydro-1,3,3-trimethyl-5-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyriddazinyl)-2H-indol-2-one ], an analogue of the cardiotonic agent indolidan, is a potent, selective and competitive inhibitor of an isozymic form of cyclic AMP phosphodiesterase. LY186126 was labelled with carbon-11 to permit pharmacological studies in the dog myocardium by positron emission tomography. Alkylation with [ 11 C]methyl iodide of N-norLY186126 (LY-197055) allowed the production of 1.7 GBq (50mCi) of [ 11 C]LY-186126 in 40 min. The product, was purified by HPLC. (author)

  7. Solvothermal synthesis and characterisation of new one-dimensional indium and gallium sulphides: [C1N4H26]0.5[InS2] and [C1N4H26]0.5[GaS2

    International Nuclear Information System (INIS)

    Vaqueiro, Paz

    2006-01-01

    Two new main group metal sulphides, [C 1 N 4 H 26 ] 0.5 [InS 2 ] (1) and [C 1 N 4 H 26 ] 0.5 [GaS 2 ] (2) have been prepared solvothermally in the presence of 1,4-bis(3-aminopropyl)piperazine and their crystal structures determined by single-crystal X-ray diffraction. Both compounds are isostructural and crystallise in the monoclinic space group P2 1 /n (Z=4), with a=6.5628(5), b=11.2008(9), c=12.6611(9) A and β=94.410(4) o (wR=0.035) for compound (1) and a=6.1094(5), b=11.2469(9), c=12.7064(10) A and β=94.313(4) o (wR=0.021) for compound (2). The structure of [C 1 N 4 H 26 ] 0.5 [MS 2 ] (M=In,Ga) consists of one-dimensional [MS 2 ] - chains which run parallel to the crystallographic a axis and are separated by diprotonated amine molecules. These materials represent the first example of solvothermally prepared one-dimensional gallium and indium sulphides. -- Graphical abstract: [C 1 N 4 H 26 ] 0.5 [InS 2 ] and [C 1 N 4 H 26 ] 0.5 [GaS 2 ], prepared under solvothermal conditions, consist of one-dimensional [MS 2 ] - chains separated by diprotonated 1,4-bis(3-aminopropyl)piperazine molecules

  8. Et2NH2C6H3(CO23SnBr2.4H2O: SYNTHESIS AND INFRARED STUDY

    Directory of Open Access Journals (Sweden)

    DAOUDA NDOYE

    2014-01-01

    Full Text Available The title compound has been obtained on allowing [C6H3(CO23(Et2NH23] to react with SnBr4. The molecular structure of Et2NH2C6H3(CO23SnBr2.4H2O has been determined on the basis of the infrared data. The suggested structure is a dimer in which each tin atom is hexacoordinated by two chelating C6H3(CO233- anions and two Br atoms. Cy2NH2+cations are involved through hydrogen bonds with non-coordinating CO2 groups. The suggested structure is a cage.

  9. Synthesis procedure for routine production of [carbonyl-{sup 11}C]desmethyl-WAY-100635

    Energy Technology Data Exchange (ETDEWEB)

    Maiti, Dilip K. [Department of Pediatrics, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Chakraborty, Pulak K. [Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States)]. E-mail: pulak@pet.wayne.edu; Chugani, Diane C. [Department of Pediatrics, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Muzik, Otto [Department of Pediatrics, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Mangner, Thomas J. [Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Chugani, Harry T. [Department of Pediatrics, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Department of Radiology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States); Department of Neurology, School of Medicine, PET Center, Children' s Hospital of Michigan, Wayne State University, 3901 Beaubien Blvd., Detroit, MI 48201 (United States)

    2005-05-01

    An improved one-pot synthesis procedure for routine production of [carbonyl-{sup 11}C]desmethyl-WAY-100635 ([{sup 11}C]DWAY) is described. An efficient purification of the crude product has also been developed and was accomplished by C-18 reversed-phase semi-preparative HPLC using 55/45 EtOH-NaH{sub 2}PO{sub 4} buffer (20mM, pH=6.5) as the eluent. The desired product fraction was collected in a 2.0-2.5mL volume and formulated with 11mL of 0.9% saline. The radioligand was ready for human use in 45min (EOB). The product was obtained with a radiochemical yield of 11.1+/-1.8% (EOB, n=15) with a radiochemical purity of >99%. Specific activity was 133.2-185.0GBq/{mu}mol (3.6-5.0Ci/{mu}mol, EOS, n=2) when ca. 37.0GBq (ca. 1.0Ci) of starting [{sup 11}C]CO{sub 2} was used. Unlabeled mass of [{sup 11}C]DWAY was found to be 0.15-0.24{mu}g/mL and the precursor was present in less than 50ng/mL in final production solution.

  10. Carbon-11 labelling of an inhibitor of acetylcholinesterase: [[sup 11]C]physostigmine

    Energy Technology Data Exchange (ETDEWEB)

    Bonnot-Lours, S.; Crouzel, C.; Prenant, C.; Hinnen, F. (CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot)

    1993-01-01

    Physostigmine, an alkaloid from calabar bean is a strong inhibitor of acetylcholinesterase and has been used clinically in the treatment of glaucoma, atropine intoxication, myasthenia gravis and more recently, in experimental trials in Alzheimer's disease. In order to study the AChE activity in the brain by positron emission tomography, we have undertaken the labelling of physostigmine with carbon-11. The synthesis involves the reaction of [[sup 11]C]methylisocyanate with eseroline. [[sup 11]C]Methylisocyanate was obtained by heating [[sup 11]C]acetylchloride with tetrabutylammonium azide in toluene. The synthesis of [[sup 11]C]CH[sub 3]COC1 involves the carbonation of methylmagnesium bromide in THF with cyclotron produced [[sup 11]C]carbon dioxide and the addition of phthaloyl dichloride. The [[sup 11]C]methylisocyanate is distilled into a solution of eseroline in ether with a small piece of sodium. After 10 minutes at 25[sup o]C, the solution is purified by HPLC and the appropriate fraction collected. Starting with 55.5 GBq (1.5 Ci) of [[sup 11]C]carbon dioxide, 0.92-1.48 GBq (25-40 mCi) of [[sup 11]C]Physostigmine are obtained 57 minutes after EOB. (author).

  11. Preclinical Evaluation of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 as Novel PET Radiotracers for Imaging Tau Aggregates in Alzheimer Disease.

    Science.gov (United States)

    Honer, Michael; Gobbi, Luca; Knust, Henner; Kuwabara, Hiroto; Muri, Dieter; Koerner, Matthias; Valentine, Heather; Dannals, Robert F; Wong, Dean F; Borroni, Edilio

    2018-04-01

    Tau aggregates and amyloid-β (Aβ) plaques are key histopathologic features in Alzheimer disease (AD) and are considered targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. This article describes the preclinical in vitro and in vivo characterization of 3 novel compounds-RO6958948, RO6931643, and RO6924963-that bind specifically to tau aggregates and have the potential to become PET tracers for future human use. Methods: RO6958948, RO6931643, and RO6924963 were identified as high-affinity competitors at the 3 H-T808 binding site on native tau aggregates in human late-stage AD brain tissue. Binding of tritiated compounds to brain tissue sections of AD patients and healthy controls was analyzed by macro- and microautoradiography and by costaining of tau aggregates and Aβ plaques on the same tissue section using specific antibodies. All 3 tracer candidates were radiolabeled with a PET nuclide and tested in vivo in tau-naïve baboons to assess brain uptake, distribution, clearance, and metabolism. Results: 3 H-RO6958948, 3 H-RO6931643, and 3 H-RO6924963 bound with high affinity and specificity to tau aggregates, clearly lacking affinity for concomitant Aβ plaques in human AD Braak V tissue sections. The specificity of all 3 radioligands for tau aggregates was supported, first, by binding patterns in AD sections comparable to the tau-specific radioligand 3 H-T808; second, by very low nonspecific binding in brain tissue devoid of tau pathology, excluding significant radioligand binding to any other central nervous system target; and third, by macroscopic and microscopic colocalization and quantitative correlation of radioligand binding and tau antibody staining on the same tissue section. RO6958948, RO6931643, and RO6924963 were successfully radiolabeled with a PET nuclide at high specific activity, radiochemical purity, and yield. After intravenous administration of 18 F-RO6958948, 11 C-RO6931643, and 11 C-RO6924963 to

  12. Radiosynthesis of 6-[C-11]-D-glucose

    International Nuclear Information System (INIS)

    Grierson, J.R.; Biskupiak, J.E.; Link, J.M.; Krohn, K.A.

    1993-01-01

    Availability of 6-[C-11]-D-glucose will permit positron emission tomography (PET) investigations of glucose utilization derived from the pentose shunt which supports biosynthesis in tissues. The first radiosynthesis of 6-[C-11]-D-glucose is described. As much as 1 mCi of 6-[C-11]-D-glucose, sufficient for animal studies, is obtained from [C-11]CO 2 after 100 min with a 16% radiochemical yield (EOB). The radiosynthesis has many attractive features. The method uses [C-11]CH 3 I and combines a Wittig reaction and a stereoselective OsO 4 catalyzed alkene hydroxylation. The OsO 4 hydroxylation of the [C-11]-labeled alkene (9) is accomplished in less than 10 min with high stereoselectivity (94:6) in favor of the 6-[C-11]-D-gluco-isomer. HPLC purification (C-18) of the protected labeled sugar removes the undesired 6-[C-11]-L-ido-sugar at an early stage and avoids the use of an expensive low-capacity ion-exchange HPLC column. OsO 4 , a highly toxic reagent, is removed in the process by adsorption and inactivation on polymer-bound triphenylphosphine. (Author)

  13. Plant uptake of bicarbonate as measured with the 11C isotope

    International Nuclear Information System (INIS)

    Wallace, A.; Mueller, R.T.; Wood, R.A.; Soufi, S.M.

    1979-01-01

    11 C which is cyclotron produced by 14 N(P, α) 11 C(half-life 20.1 M) was used as a tracer of bicarbonate to determine its movements from a nutrient solution through roots to stems and leaves of bush bean plants (Phaseolus vulgaris L. var Improved Tendergreen). The short time involved and the high solution pH minimized the need for use of the Henderson Hasselbach equation for activity correction. Quantities of 11 C did move into roots, stems and leaves with a sharp decreasing gradient (root/stem = 14.5, stems/leaves = 11.7) More 11 C moved into plants with KHCO 3 than with NaHCO 3 . The (NH 4 ) 2 SO 4 enhanced 11 C uptake and KNO 3 decreased it. This enhancement and competition indicated possibility of some uptake of HCO 3 - . In an experiment with Galenia pubescens (Eckl. and Zeyh.) Druce, the 11 C was more readily moved to stems and leaves than in bush bean indicating substantial uptake of HCO 3 - . (Auth.)

  14. [11C] Methionine as PET radiopharmaceutical produced at CDTN/CNEN

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina B.; Ferreira, Soraya Z.; Carvalho, Tiago F.; Silva, Juliana B. da, E-mail: mbs@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos

    2013-07-01

    Carbon-11 ({sup 11}C) is an attractive radionuclide used in positron emission tomography (PET) since carbon is a ubiquitous element in biomolecules. Positron emitter-labeled amino acids are being widely used as indicators of tumor activity due to enhanced expression of amino acid transporter systems in cancer cells. L-[Methyl-({sup 11}C)] Methionine or [{sup 11}C]Methionine is being used in neuro-oncology and, unlike 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ({sup 18}FDG), gives more contrast images and improves brain tumor diagnosis. The aim of this work was to develop the synthesis and quality control of [{sup 11}C]Methionine at the Radiopharmaceuticals Research and Production Facility (UPPR) of CDTN/CNEN. The synthesis of [{sup 11}C] Methionine was performed using two Sep-Pak tC18 plus cartridges one as solid support for the {sup 11}C-methylation of the precursor L-homocysteine thiolactone hydrochloride and another for purification. The pH, radionuclidic identity and purity, residual solvents, radiochemical and chemical purity of the final product were evaluated as described on the European Pharmacopoeia 7.0 monograph. Total synthesis time was 18 minutes, the radiochemical yield was approximately 15% (non-decay corrected) and radiochemical purity was greater than 95%. [{sup 11}C]Methionine was successfully synthesized at CDTN using the described procedures and complied with quality requirements. Due to the rapid growth of oncologic PET scans in last decade, {sup 11}C labelling holds great promises in the next few years with the application of other tracers beyond {sup 18}FDG. This pioneering work of UPPR/CDTN represents a response to the demands of a growing nuclear medicine in the country focused on achieving better diagnostic imaging. (author)

  15. Synthesis and evaluation of racemic [11C]NS2456 and its enantiomers as selective serotonin reuptake radiotracers for PET

    International Nuclear Information System (INIS)

    Smith, D.F.; Bender, D.; Marthi, K.; Cumming, P.; Hansen, S.B.; Peters, D.; Oestergaard Nielsen, E.; Scheel-Krueger, J.; Gjedde, A.

    2001-01-01

    Positron emission tomography (PET) radiotracers are needed for quantifying serotonin uptake sites in the living brain. Therefore, we evaluated a new selective serotonin reuptake inhibitor, NS2456, to determine whether it is suited for use in PET. Racemic NS2456 [(1RS,5SR)-8-methyl-3-[4-trifluoromethoxyphenyl]-8-azabicyclo [3.2.1]oct-2-ene] and its N-demethylated analog, racemic NS2463, selectively inhibited serotonin uptake in rat brain synaptosomes; their IC 50 values were 3000-fold lower for [ 3 H]serotonin than for either [ 3 H]dopamine or [ 3 H]noradrenaline. The enantiomers of NS2463 were also potent inhibitors of serotonin uptake in vitro, but they failed to show stereoselectivity. Racemic NS2463 as well as its enantiomers were radiolabelled by N-methylation with C-11, yielding [ 11 C]NS2456 for use in PET of the living porcine brain. The compounds crossed the blood-brain barrier rapidly and accumulated preferentially in regions rich in serotonin uptake sites (e.g., brainstem, subthalamus and thalamus). However, their binding potentials were relatively low and no stereoselectivity was found. Thus, neither racemic [ 11 C]NS2456 nor its [ 11 C]-labelled enantiomers are ideal for PET neuroimaging of neuronal serotonin uptake sites

  16. Crystal structure of 2-amino-1,3-dibromo-6-oxo-5,6-dihydropyrido[1,2-a]quinoxalin-11-ium bromide monohydrate

    Directory of Open Access Journals (Sweden)

    Md. Serajul Haque Faizi

    2015-11-01

    Full Text Available In the title hydrated salt, C12H8Br2N3O+·Br−·H2O, which was synthesized by the reaction of the pyridine derivative Schiff base N1,N4-bis(pyridine-2-ylmethylenebenzene-1,4-diamine with bromine, the asymmetric unit contains a 2-amino-1,3-dibromo-6-oxo-5,6-dihydropyrido[1,2-a]quinoxalin-11-ium cation, with a protonated pyridine moiety, a bromide anion and a water molecule of solvation. The cation is non-planar with the dibromo-substituted benzene ring, forming dihedral angles of 24.3 (4 and 11.5 (4° with the fused pyridine and pyrazine ring moieties, respectively. In the crystal, the cations are linked through a centrosymmetric hydrogen-bonded cyclic R42(8 Br2(H2O2 unit by N—H...Br, N—H...O and O—H...Br hydrogen bonds, forming one-dimensional ribbons extending along b, with the planes of the cations lying parallel to (100.

  17. Mild synthesis of [N-methyl-11C]-isovaleroyl-(L)-carnitine. The usefulness of a tritium approach

    International Nuclear Information System (INIS)

    Angelini, G.; Carnevaletti, F.; Margonelli, A.; Corsi, G.; Ragni, P.; Fazio, F.; Todde, S.; Tinti, O.

    1999-01-01

    The title carnitine derivative was labelled both with [ 11 C]methyl iodide and [ 3 H]methyl iodide. The former was synthesized in order to improve the knowledge of the acyl carnitines fate in humans. The latter was synthesized, at approximately the same concentration level as that of the former, in order to optimize its radiosynthesis, taking advantage from the long half-life of the tritium

  18. Chemical Behaviour of C{sup 11} in Liquid Hydrocarbons; Comportement Chimique de {sup 11}C dans les Hydrocarbures Liquides; Khimicheskaya kharakteristika ugleroda-11 v zhidkikh uglevodorodakh; Comportamiento Quimico del {sup 11}C en Hidrocarburos Liquidos

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, A. F.; Clark, D. E.; Mesich, F. G. [Institute of Atomic Research and Department of Chemistry, Iowa State University, Ames, IA (United States)

    1965-04-15

    Carbon-11 is produced by the C{sup 12} ({gamma}, n)Cu{sup 11} reaction in the Bremsstrahlung beam of a 70 MeV electron synchrotron. As target materials, liquid hydrocarbons with 5 and 6 carbons have been used, including normal, branched and alicyclic pentanes and hexanes as well as benzene. The behaviour of Cu{sup 11} has been studied by gas chromatographic separation of the products, counting the Cu{sup 11} in the gas stream in a cell placed in a well-type scintillation counter. In each experiment yields of different products were compared to the yield of acetylene as an internal standard and either to a tantalum monitor or to the total Cu{sup 11} produced as measured in the entire sample before separation. The flow counters were calibrated in terms of total Cu{sup 11} produced in experiments in which the complete sample was burned to CO{sub 2} and passed through a flow counter. Our earlier experiments were concerned only with the gaseous products that have now been well characterized for the various target molecules under different dosage conditions. Current experiments on product molecules similar in size to the target have proved very helpful in deciding on mechanisms for recombination of recoil atoms. Of particular interest is the yield of product with one carbon more than the target,the result of an addition reaction. The location of the additional atom on a target molecule having several types of addition sites gives information regarding the process itself. When the recoil atom is slowed to an energy at which it is possible for a bond to be formed, at least temporarily, the extra energy which the Cu{sup 11} atom brings into the system may cause bond rupture elsewhere within the activated complex usually leading to a two-carbon product. If the complex is able to hold together without rupturing, an additional product will result. Thus comparison of the yields of two-carbon compounds, acetylene, ethylene and ethane, and the additional products provides

  19. Elastic enhancement factor in the 11B(p,n0)11C reaction at Ep=14.3 MeV

    International Nuclear Information System (INIS)

    Hussein, M.S.; Pessoa, E.F.; Schelin, H.R.; Carlson, B.V.; Douglas, R.A.

    1985-01-01

    The elastic enhancement factor in charge exchange reactions proceeding via the compound nucleus, predicted to attain the value of 2 in the weak isospin mixing regime by Harney, Weidenmuller and Richter five years ago, is tested here in the system 11 B(p,n) 11 C at = 14.3 MeV. Both the DWBA and Hauser-Feshbach calculations employed in the analysis are used in a way which physically simulates a two coupled-channels model. Our results show an enhancement factor larger than 1 indicating that isospin is mainly conserved in this reaction. (Author) [pt

  20. Crystallization and Characterization of a New Magnesium Sulfate Hydrate MgSO4.11H2O

    NARCIS (Netherlands)

    Genceli, F.E.; Lutz, M.; Spek, A.L.; Witkamp, G.J.

    2007-01-01

    The MgSO4 crystal hydrate formed below approximately 0 °C was proven to be the undecahydrate, MgSO4 • 11H2O (meridianiite) instead of the reported dodecahydrate MgSO4 • 12H2O. The crystals were grown from solution by eutectic freeze and by cooling crystallization. The crystal structure analysis and

  1. Improved synthesis and application of [(11) C]benzyl iodide in positron emission tomography radiotracer production.

    Science.gov (United States)

    Pekošak, Aleksandra; Filp, Ulrike; Rotteveel, Lonneke; Poot, Alex J; Windhorst, Albert D

    2015-06-30

    Positron emission tomography has increased the demand for new carbon-11 radiolabeled tracers and building blocks. A promising radiolabeling synthon is [(11) C]benzyl iodide ([(11) C]BnI), because the benzyl group is a widely present functionality in biologically active compounds. Unfortunately, synthesis of [(11) C]BnI has received little attention, resulting in limited application. Therefore, we investigated the synthesis in order to significantly improve, automate, and apply it for labeling of the dopamine D2 antagonist [(11) C]clebopride as a proof of concept. [(11) C]BnI was synthesized from [(11) C]CO2 via a Grignard reaction and purified prior the reaction with desbenzyl clebopride. According to a one-pot procedure, [(11) C]BnI was synthesized in 11 min from [(11) C]CO2 with high yield, purity, and specific activity, 52 ± 3% (end of the cyclotron bombardment), 95 ± 3%, and 123 ± 17 GBq/µmol (end of the synthesis), respectively. Changes in the [(11) C]BnI synthesis are reduced amounts of reagents, a lower temperature in the Grignard reaction, and the introduction of a solid-phase intermediate purification. [(11) C]Clebopride was synthesized within 28 min from [(11) C]CO2 in an isolated decay-corrected yield of 11 ± 3% (end of the cyclotron bombardment) with a purity of >98% and specific activity (SA) of 54 ± 4 GBq/µmol (n = 3) at the end of the synthesis. Conversion of [(11) C]BnI to product was 82 ± 11%. The reliable synthesis of [(11) C]BnI allows the broad application of this synthon in positron emission tomography radiopharmaceutical development. Copyright © 2015 John Wiley & Sons, Ltd.

  2. (1-Phenyl-1H-1,2,3-triazol-4-ylmethyl pyridine-3-carboxylate

    Directory of Open Access Journals (Sweden)

    Zakirjon Karimov

    2010-07-01

    Full Text Available In the title compound, C15H12N4O2, the dihedral angle between the planes of the nicotinoyloxy fragment and triazole ring is 88.61 (5°. The dihedral angle between the planes of triazole and benzene rings is 16.54 (11°. The crystal structure is stabilized by intermolecular C—H...N, C—H...O and C—H...π(triazole hydrogen bonds and aromatic π–π stacking interactions between the benzene and triazole rings [centroid–centroid distance = 3.895 (1 Å

  3. 1-[(6-Chloro-3-pyridylmethyl]-N-(4-ethoxyphenyl-3-phenyl-1H-pyrazole-5-carboxamide

    Directory of Open Access Journals (Sweden)

    Zheng Tang

    2009-04-01

    Full Text Available In the title compound, C24H21ClN4O2, the pyrazole ring makes dihedral angles of 7.70 (11, 89.17 (11 and 40.68 (11° with the phenyl, pyridine and ethoxyphenyl rings, respectively. There are some intramolecular C—H...O and C—H...π bonds giving rigidity to the molecule, while weak intermolecular N—H...N and C—H...π hydrogen bonds link the molecules into a two-dimensional structure.

  4. 3-[4-(10H-Indolo[3,2-b]quinolin-11-ylpiperazin-1-yl]propan-1-ol

    Directory of Open Access Journals (Sweden)

    Gary S. Nichol

    2011-12-01

    Full Text Available In the title compound, C22H24N4O, the aromatic moiety is essentially planar (r.m.s. deviation of a least-squares plane fitted through all non-H atoms = 0.0386 Å and is rotated by 89.98 (4° from the piperazine ring, which adopts the expected chair conformation. The propanol chain is not fully extended away from the piperazine ring. In the crystal, there are two unique hydrogen-bonding interactions. One is an O—H...N interaction which, together with an inversion-related symmetry equivalent, forms a ring motif. The second is an N—H...N interaction which links adjacent molecules by means of a chain motif which propagates in the c-axis direction. Overall, a two-dimensional hydrogen-bonded structure is formed.

  5. (2R,3aR,4S,7R,7aS,9R,10aR,11S,14R,14aS-rel-3a,4,7,7a,10a,11,14,14a-Octahydro-4,14:7,11-diepoxy-2,9-propanonaphtho[1,2-f:5,6-f′]diisoindole-1,3,8,10-tetrone (9CI: a cyclophane derived from naphtho[1,2-c:5,6-c]difuran

    Directory of Open Access Journals (Sweden)

    Peter W. Dibble

    2008-09-01

    Full Text Available The title compound, C25H18N2O6, is a naphthalenophane styled in the manner of Warrener's alicyclic cyclophanes or molecular racks wherein a trimethylene tether is perfectly staggered between the two N atoms such that the central methylene H atoms point toward the naphthalene π-system. The dihedral angle between the mean planes of the two benzene rings is 7.61 (7°.

  6. (5S-4-(2,2-Dimethylpropyl-5-isopropyl-1,3,4-oxadiazinan-2-one

    Directory of Open Access Journals (Sweden)

    Kate L. Edler

    2010-12-01

    Full Text Available The title compound, C11H22N2O2, has one chiral center and packs in the monoclinic space group P21. The asymmetric unit has five crystallographically independent molecules, four of which engage in intermolecular N—H...O hydrogen bonding.

  7. Synthesis of n. c. a. PET-radiotracers with carbon-11. Zur Synthese traegerarme PET-Radiotracer mit Kohlenstoff-11

    Energy Technology Data Exchange (ETDEWEB)

    Schirbel, A.

    1998-11-01

    Carbon-11 offers the unique possibility of authentic labelling of molecules as radioindicators for non invasive and quantitative determination of physiological functions via positron emission tomography (PET). Therefore, the goal of this thesis was to synthesize of different n.c.a. [sup 11]C-labelled pharmaceuticals for in vivo distribution studies with PET. For the determination of the pharmacokinetics of [1-[sup 11]C]acetate in porcine myocardium during prolonged ischemia, n.c.a. [1-[sup 11]C]acetate was synthesized via carboxylation of methylmagnesium bromide with in target produced n.c.a. [[sup 11]C]CO[sub 2] with a radiochemical yield (RCY) of 68 [+-] 7%. The fast (18 min) and reliable radiosynthesis allowed for repeated tracer administration at short intervals (<20 min). In order to study the pharmacokinetics and metabolism of acetylsalicylic acid (Aspirin[sup R]c) in humans, [1-[sup 11]C]acetylsalicylic acid, acetyl-[carboxy-[sup 11]C]salicylic acid and [carboxy-[sup 11]C]salicylic acid were prepared. N.c.a. [1-[sup 11]C]acetylsalicylic acid was synthesized via the reaction of [1-[sup 11]C]acetylchloride with salicylic acid salts. The use of the silver salt proved to be superior to the sodium salt and resulted in radiochemical yields of 32 [+-] 5%. Base-line (clean) separation of the labelled product was achieved using radio-HPLC. With regard to the preparation of n.c.a. [carboxy-[sup 11]C]salicylic acid, several protected and unprotected phenol derivates were metallated and subsequently carboxylated using n.c.a. [[sup 11]C]CO[sub 2]. Best results (87 [+-] 3% RCY) could be achieved with 2-(methoxymethoxy)-phenylmagnesium iodide as a precursor and subsequent quantitative cleavage of the MOM-group. Acetylation of n.c.a. [carboxy-[sup 11]C]salicylic acid to acetyl-[carboxy-[sup 11]C]salicylic acid was performed using acetylchloride in CH[sub 2]Cl[sub 2] with a radiochemical yield of 65 [+-] 4%. (orig.)

  8. Structure of poly[diaqua[μ-1,2-bis(pyridin-4-ylethane-κ2N:N′]bis(μ3-cyclobutane-1,1-dicarboxylato-κ3O,O′:O′′:O′′′dimanganese(II

    Directory of Open Access Journals (Sweden)

    Do Nam Lee

    2015-08-01

    Full Text Available In the title compound, [Mn(C6H6O4(C12H12N2(H2O]n, the cyclobutane-1,1-dicarboxylate (cbdc ligands bridge three MnII ions, forming layers parallel to the ac plane. These layers are additionally connected by 1,2-bis(pyridin-4-ylethane ligands to form a three-dimensional polymeric framework. An inversion centre is located at the mid-point of the central C—C bond of the 1,2-bis(pyridin-4-ylethane ligand. The coordination geometry of the MnII ion is distorted octahedral and is built up by four carboxylate O atoms, one water O atom and a pyridyl N atom. The pyridine ligand and the coordinating water molecule are in a trans configuration. One carboxylate group of the cbdc ligand acts as a chelating ligand towards one MnII atom, whereas the second carboxylate group coordinates two different MnII atoms.

  9. Modified synthesis of 11-[{sup 14}C]-clozapine

    Energy Technology Data Exchange (ETDEWEB)

    Matloubi, Hojatollah E-mail: hmatloubi@seai.neda.net.ir; Ghandi, Mehdi; Zarrindast, M.-R.; Saemian, Nader

    2001-11-01

    The reported synthetic pathway of 8-chloro-11-(4-methyl-1-piperazinyl)-11-[{sup 14}C]-5H-dibenzo[b,e][1,4]diazapine (clozapine) was modified in several steps. The synthetic pathway was shortened by 60% and the total yield was increased from 6% to 23%.

  10. Amyloid imaging in cognitively normal older adults: comparison between 18F-flutemetamol and 11C-Pittsburgh compound B

    International Nuclear Information System (INIS)

    Adamczuk, Katarzyna; Schaeverbeke, Jolien; Neyens, Veerle; Dupont, Patrick; Nelissen, Natalie; Vandenbulcke, Mathieu; Goffin, Karolien; Lilja, Johan; Hilven, Kelly; Laere, Koen van; Vandenberghe, Rik

    2016-01-01

    Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: 18 F-flutemetamol and 11 C-Pittsburgh compound B (PIB). In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on 18 F-flutemetamol versus 11 C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVR comp ) and, alternatively, according to visual reads. We also determined the correlation between 18 F-flutemetamol and 11 C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. Binary classification based on semiquantitative assessment was concordant between 18 F-flutemetamol and 11 C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between 18 F-flutemetamol and 11 C-PIB SUVR comp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. For the definition of preclinical AD based on 18 F-flutemetamol, concordance with 11 C-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region. (orig.)

  11. (11-Methylpyrido[2,3-b][1,4]benzodiazepin-6-yl(phenylmethanone

    Directory of Open Access Journals (Sweden)

    Fuqiang Shi

    2010-09-01

    Full Text Available In the title compound, C20H15N3O, the diazepine ring adopts a boat conformation. The dihedral angle between pyridine and benzene rings is 55.2 (1°. The benzoyl phenyl ring forms dihedral angles of 49.4 (1 and 75.9 (1°, respectively, with the pyridine and benzene rings. In the crystal, molecules are linked into centrosymmetric dimers by pairs of C—H...N hydrogen bonds.

  12. Avocado roots treated with salicylic acid produce phenol-2,4-bis (1,1-dimethylethyl), a compound with antifungal activity.

    Science.gov (United States)

    Rangel-Sánchez, Gerardo; Castro-Mercado, Elda; García-Pineda, Ernesto

    2014-02-15

    We demonstrated the ability of salicylic acid (SA) to induce a compound in avocado roots that strengthens their defense against Phytophthora cinnamomi. The SA content of avocado roots, before and after the application of exogenous SA, was determined by High-Performance Liquid Chromatography (HPLC). After 4h of SA feeding, the endogenous level in the roots increased to 223 μg g(-1) FW, which was 15 times the amount found in control roots. The methanolic extract obtained from SA-treated avocado roots inhibited the radial growth of P. cinnamomi. A thin layer chromatographic bioassay with the methanolic extract and spores of Aspergillus showed a distinct inhibition zone. The compound responsible for the inhibition was identified as phenol-2,4-bis (1,1-dimethylethyl) by gas chromatography and mass spectrometry. At a concentration of 100 μg/mL, the substance reduced germinative tube length in Aspergillus and radial growth of P. cinnamomi. A commercial preparation of phenol-2,4-bis (1,1-dimethylethyl) caused the same effects on mycelium morphology and radial growth as our isolate, confirming the presence of this compound in the root extracts. This is the first report of the induction of this compound in plants by SA, and the results suggest that it plays an important role in the defense response of avocado. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. Positioning of the carboxamide side chain in 11-oxo-11H-indeno[1,2-b]quinolinecarboxamide anticancer agents: effects on cytotoxicity.

    Science.gov (United States)

    Deady, L W; Desneves, J; Kaye, A J; Finlay, G J; Baguley, B C; Denny, W A

    2001-02-01

    A series of 11-oxo-11H-indeno[1,2-b]quinolines bearing a carboxamide-linked cationic side chain at various positions on the chromophore was studied to determine structure-activity relationships between cytotoxicity and the position of the side chain. The compounds were prepared by Pfitzinger synthesis from an appropriate isatin and 1-indanone, followed by various oxidative steps, to generate the required carboxylic acids. The 4- and 6-carboxamides (with the side chain on a terminal ring, off the short axis of the chromophore) were effective cytotoxins. The dimeric 4- and 6-linked analogues were considerably more cytotoxic than the parent monomers, but had broadly similar activities. In contrast, analogues with side chains at the 8-position (on a terminal ring but off the long axis of the chromophore) or 10-position (off the short axis of the chromophore but in a central ring) were drastically less effective. The 4,10- and 6,10-biscarboxamides had activities between those of the corresponding parent monocarboxamides. The first of these showed good activity against advanced subcutaneous colon 38 tumours in mice.

  14. A study of the 10, 11B(p,n)10, 11C reactions between Ep=13,7 and 14,7 MeV

    International Nuclear Information System (INIS)

    Schelin, H.R.

    1985-01-01

    Using time-of-flight facilities of the Sao Paulo 8UD Pelletron Accelerator, absolute differential cross sections for the n 0 , n 1 , n 2 , n 3 , (n 4 +n 5 ), n 6 and n 7 groups for the reaction 11 B(p,n) 11 C and the n 0 and n 1 neutron groups for the reaction 10 B(p,n) 10 C have been measured at incident proton energies of 14.0, 14.3 and 14.6 MeV in the angular interval of 20 to 160 degrees. Excitation functions at θ lab =20 deg from Ep=13.7 to 14.7 MeV in intervals of 100 KeV were also measured. The theoretical analysis was conducted to determine relative contributions of the diret and compound nucleus processes in the differential cross sections. To this end, a two couple channel model model for the reactions was assumed. The DWBA model for the direct and the Hauser-Feshbch for the compound nucleus processes were in such a way as to simulate the exact coupled channels calculation through an appropriate choice of the absorption term W in the optical potential. The results indicate that about half of the cross section is due to the compound nucleus mechanism. The theoretical analysis aimed at obtaining the elastic enhancement factor for the channel 11 B(p,n 0 ) 11 C at Ep=14.3 MeV. This has been demonstrated to appear in compound nucleus charge reactions by Harney, Weidemueller and Richter and predicted to attain the value 2 when isospin is conserved. Our results show an enhancement factor larger than 1 indicating that isospin mixing is weak in this reaction. (Author) [pt

  15. Synthesis of some 11C-labelled alkaloids

    International Nuclear Information System (INIS)

    Laangstroem, B.; Antoni, G.; Halldin, H.; Svaerd, H.; Bergson, G.

    1982-01-01

    Using ( 11 C)-methyl iodide in N-alkylation reactions in dimethylformamide (DMF), the alkaloids N-( 11 C-methyl)-morphine, N-( 11 C-methyl)-codeine, 6-N(methyl)-9, 10-dihydroergotamine, 6-N-( 11 C-methyl)-bromocriptine and N-( 11 C-methyl)-nicotine have been synthesized in radiochemical yields of 50-95%, within 5-10 min of introducing ( 11 C)-methyl iodide into the reaction vial. ( 11 C)-Methyl iodide was obtained within 4-7 min from ( 11 C)-carbon dioxide prepared by the 14 N(p,α) 11 C reaction. (Authors)

  16. 5-(4-Methylphenylsulfonyl-1,3-dithiolo[4,5-c]pyrrole-2-thione

    Directory of Open Access Journals (Sweden)

    Ning-Juan Zheng

    2012-04-01

    Full Text Available The asymmetric unit of the title compound, C12H9NO2S4, contains one half-molecule with the N, two S amd four C atoms lying on a mirror plane. The molecule exhibits a V-shaped conformation, with a dihedral angle of 87.00 (7° between the benzene and dithiolopyrrole rings. The methyl group was treated as rotationally disordered between two orientations in a 1:1 ratio. In the crystal, weak C—H...O hydrogen bonds link the molecules into chains in [010].

  17. Production of [11C]CO2 with gas target at low proton energies

    International Nuclear Information System (INIS)

    Sansaloni, Francesc; Lagares, Juan Ignacio; Llop, Jordi; Arce, Pedro; Díaz, Carlos; Pérez-Morales, José Manuel

    2013-01-01

    Nowadays the demand and the installation of self-shielded low-energy cyclotrons is growing, allowing the use of 11 C in many more centers. The aim of this study was the design of a new target and the evaluation of the production of 11 C as [ 11 C]CO 2 at low proton energies. The target was coupled to an IBA Cyclone-18/9 and the energy was decreased to 4–16 MeV. The newly designed target allowed the production of [ 11 C]CO 2 at different proton energies, and the results suggest that the cyclotron energy of Cyclone-18/9 is slightly higher than the nominal 18 MeV

  18. Automated photosynthesis of 11C-glucose

    International Nuclear Information System (INIS)

    Ishiwata, K.; Monma, M.; Iwata, R.; Ido, T.

    1982-01-01

    Glucose and fructose, labelled with 11 C, were produced by passing 11 CO 2 into an evacuated chamber containing spinach leaves. Photosynthesis was carried out by day light lamp illumination. 75-95% of the 11 CO 2 was absorbed by the leaves and the radioactivity in the leaves was extracted in ethanol as sugars. Radiochemical purity was determined by HPLC. The automated system was controlled by timers. (U.K.)

  19. Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain

    International Nuclear Information System (INIS)

    Ishiwata, K.; Senda, M.; Saitoh, T.; Taguchi, K.; Toda, J.; Sano, T.; Koyanagi, Y.

    2001-01-01

    We investigated the effects of intraperitoneal injection of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the binding of [ 11 C]raclopride to striatal dopamine D 2 receptors in mice. The binding of [ 11 C]raclopride, but not of [ 11 C]N-methylspiperone or [ 11 C]nemonapride with higher affinity, to the receptors was significantly decreased immediately after TIQ injection. Neither a dopamine transporter blocker induced such effect nor TIQ affected the dopamine transporter-radioligand binding. Among the compounds investigated, including parkinsonism-inducing TIQ and (R/S)-1-benzyl-TIQ, parkinsonism-preventing (R)- and (S)-1-methyl-TIQ, and probable N-methylated metabolites of TIQ and 1-methyl-TIQ, TIQ and (S)-1-methyl-TIQ had the strongest effect on the binding of [ 11 C]raclopride, and N-methylated derivatives showed less of an effect than the respective parent compounds. The decrease in the binding of [ 11 C]raclopride continued for 7 hours and was followed by an increase until 10 days after the single and subchronic administration of TIQ. These findings suggest that TIQ analogs profoundly stimulated dopamine release which resulted in the competitive inhibition of the binding of [ 11 C]raclopride to dopamine D 2 receptors, but did not induce degeneration of the receptors. (author)

  20. (3-Benzoyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-olato-κ2O,Obis[2-(2-pyridylphenyl-κ2C1,N]iridium(III

    Directory of Open Access Journals (Sweden)

    Kaijun Luo

    2011-11-01

    Full Text Available The title compound, [Ir(C11H8N2(C17H19O2], has an octahedral coordination geometry around the IrIII atom, retaining the cis-C,C,trans–N,N chelate disposition of the two 2-phenylpyridine ligands. The chelate rings are nearly mutually perpendicular [the interplanar angles range from 85.48 (17 to 89.17 (19°]. The two 2-(2-pyridylphenyl ligands are approximately planar, with the plane of the phenyl ring being inclined to that of the pyridine ring by 2.3 (3 and 5.1 (3° in the two ligands. The interplanar angle between the phenyl ring in 3-benzoyl-camphor and the IrO2C3 chelate ring is 35.5 (2°.

  1. Osseous associated cervical spondylomyelopathy at the C2-C3 articular facet joint in 11 dogs.

    Science.gov (United States)

    Cooper, C; Gutierrez-Quintana, R; Penderis, J; Gonçalves, R

    2015-11-21

    In dogs, vertebral canal stenosis at C2-C3 due to articular facet joint degeneration is only sporadically identified. The authors' aims were to review the clinical presentation, MRI characteristics, treatment and outcome of dogs presenting with this condition. Eleven cases were eligible for inclusion. Neurological examination revealed tetraparesis and proprioceptive ataxia in all 4 limbs in 3/11, proprioceptive tetra-ataxia only in 4/11, pelvic limb proprioceptive ataxia in 2/11 and no gait abnormalities in 2/11 dogs. Cervical hyperaesthesia was present in 7/11 dogs. MRI revealed bilateral articular facet joint degeneration in 10/11 cases and unilateral degeneration in one. Surgery was performed in six cases and medical management elected in five. Long-term follow-up information was available for 11 animals. Four of the surgical cases are alive and have no neurological deficits, one was euthanased for an unrelated condition and one lost to follow-up. Of the cases managed medically, three are alive showing no neurological deficits, one is alive still displaying neurological deficits and one euthanased for an unrelated condition whilst still ataxic. This study shows that both medical and surgical management can result in good outcomes in dogs with vertebral canal stenosis resulting from articular facet joint degeneration at the level of C2-C3. British Veterinary Association.

  2. 2,2′-Dimethyl-1,1′-[2,2-bis(bromomethylpropane-1,3-diyl]dibenzimidazole hemihydrate

    Directory of Open Access Journals (Sweden)

    Yong-Sheng Yan

    2012-03-01

    Full Text Available The title compound, C21H22Br2N4·0.5H2O, contains two benzimidazole groups which may provide two potential coordination nodes for the construction of metal–organic frameworks. The mean planes of the two imidazole groups are almost perpendicular, with a dihedral angle of 83.05 (2°, and adjacent molecules are linked into a one-dimensional chain by π–π stacking interactions between imidazole groups of different molecules [centroid-to-centroid distances of 3.834 (2 and 3.522 (2 Å].

  3. 2,2′-[1,1′-(Heptane-1,7-diyldioxydinitrilodiethylidyne]di-1-naphthol

    Directory of Open Access Journals (Sweden)

    Wen-Kui Dong

    2009-07-01

    Full Text Available The molecule of the title compound, C31H34N2O4, adopts an L-shaped configuration, in which the naphthalene units are approximately perpendicular, making a dihedral angle of 87.89 (3°. Intramolecular H-bonds are formed between the OH substituents and the N atoms at each end of the molecule. In the crystal structure, each molecule links six other molecules into an infinite three-dimensional network supramolecular structure, which is built from one-dimensional zigzag chains via weak C—H...π stacking and intermolecular C—H...O hydrogen bonds.

  4. Low temperature synthesis of no-carrier-added [{sup 11}C]formaldehyde with metal hydrides and preparation of [1-{sup 11}C]1,2,3,4-Tetrahydro-{beta}-Carboline Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Nader, M.W.; Zeisler, S.K.; Theobald, A.; Oberdorfer, F

    1998-12-01

    A comparative study has been performed on the selective reduction of cyclotron-produced [{sup 11}C]carbon dioxide to [{sup 11}C]formaldehyde with solutions of various complex metal hydrides at temperatures between -52 and +25 deg. C. Under optimal reaction conditions, lithium tetrahydridoaluminate gave the highest yield of [{sup 11}C]formaldehyde (58%, decay-corrected), followed by lithium triethylhydridoborate (34%) and sodium tetrahydridoborate (22%). Radiochemically pure [{sup 11}C]formaldehyde could be obtained with lithium tetrahydridoaluminate and sodium tetrahydridoborate, but not with lithium triethyl hydridoborate. The produced [{sup 11}C]formaldehyde was used for the synthesis of [1-{sup 11}C]1,2,3,4-tetrahydro-{beta}-carboline derivatives by the Pictet-Spengler reaction.

  5. Poly[[μ2-2,2′-diethyl-1,1′-(butane-1,4-diyldiimidazole-κ2N3:N3′](μ2-5-hydroxyisophthalato-κ2O1:O3zinc

    Directory of Open Access Journals (Sweden)

    Ying-Ying Liu

    2011-11-01

    Full Text Available In the title coordination polymer, [Zn(C8H4O5(C14H22N4]n, the ZnII cation is coordinated by an O2N2 donor set in a distorted tetrahedral geometry. The ZnII ions are linked by μ2-OH-bdc (OH-H2bdc = 5-hydroxyisophthalic acid and bbie ligands [bbie = 2,2′-diethyl-1,1′-(butane-1,4-diyldiimidazole], forming a two-dimensional layer parallel to the ab plane. The layers are further connected through intermolecular C—H...O and O—H...O hydrogen bonds, forming a three-dimensional supramolecular structure. In the bbie ligand, the two C atoms in the ethyl group are each disordered over two positions with a site-occupancy ratio of 0.69:0.31.

  6. 11 CFR 110.11 - Communications; advertising; disclaimers (2 U.S.C 441d).

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Communications; advertising; disclaimers (2 U.S... AND EXPENDITURE LIMITATIONS AND PROHIBITIONS § 110.11 Communications; advertising; disclaimers (2 U.S... through radio or television, or through any broadcast, cable, or satellite transmission, must comply with...

  7. 1,1′-[Imidazolidine-1,3-diylbis(methylene]bis(1H-benzotriazole

    Directory of Open Access Journals (Sweden)

    Augusto Rivera

    2012-02-01

    Full Text Available In the title compound, C17H18N8, the imidazolidine ring adopts an envelope conformation with the substituents at the N atoms in trans positions with respect to the central ring. The dihedral angle between the two benzotriazole rings is 71.65 (10°. In the crystal, non-classical C—H...N interactions link the molecules into helical chains along the b axis. The crystal packing is further stabilized by weak C—H...π interactions.

  8. Crystal structure of 2,2′′-bis(2,7-dichloro-9-hydroxy-9H-fluoren-9-yl-1,1′:4′,1′′-terphenyl triethylamine trisolvate

    Directory of Open Access Journals (Sweden)

    Henrik Klien

    2015-12-01

    Full Text Available In the title solvate, C44H26Cl4O2·3C6H15N, the asymmetric part of the unit cell comprises two halves of the diol molecules, 2,2′′-bis(2,7-dichloro-9-hydroxy-9H-fluoren-9-yl-1,1′:4′,1′′-terphenyl, and three molecules of triethylamine, i. e. the diol molecules are located on crystallographic symmetry centres. Two of the solvent molecules are disordered over two positions [occupancy ratios of 0.567 (3:0.433 (3 and 0.503 (3:0.497 (3]. In the diol molecules, the outer rings of the 1,1′:4′,1′′-terphenyl elements are twisted with reference to their central arene ring and the mean planes of the fluorenyl moieties are inclined with respect to the terphenyl ring to which they are connected, the latter making dihedral angles of 82.05 (8 and 82.28 (8°. The presence of two 9-fluoren-9-ol units attached at positions 2 and 2′′ of the terphenyl moiety induces a `folded' geometry which is stabilized by intramolecular C—H...O hydrogen bonds and π–π stacking interactions, the latter formed between the fluorenyl units and the central ring of the terphenyl unit [centroid–centroid distances = 3.559 (1 and 3.562 (1 Å]. The crystal is composed of 1:2 complex units, in which the solvent molecules are associated with the diol molecules via O—H...N hydrogen bonds, while the remaining solvent molecule is linked to the host by a C—H...N hydrogen bond. The given pattern of intermolecular interactions results in formation of chain structures extending along [010].

  9. Mild synthesis of [N-methyl-{sup 11}C]-isovaleroyl-(L)-carnitine. The usefulness of a tritium approach

    Energy Technology Data Exchange (ETDEWEB)

    Angelini, G.; Carnevaletti, F.; Margonelli, A.; Corsi, G. [Istituto di Chimica Nucleare - C.N.R., C.P. 10, Rome (Italy); Ragni, P. [Istituto di Chimica Nucleare -- C.N.R., C.P. 10 -- 00016 Monterotondo Stazione, Roma, (Italy); Fazio, F.; Todde, S. [Istituto di Neuroscienze e Bioimmagini - C.N.R., H.S. Raffaele, Milan (Italy); Tinti, O. [Sigma-Tau, Industrie Farmaceutiche Riunite S.p.A., Pomezia, Rome (Italy)

    1999-02-01

    The title carnitine derivative was labelled both with [{sup 11}C]methyl iodide and [{sup 3}H]methyl iodide. The former was synthesized in order to improve the knowledge of the acyl carnitines fate in humans. The latter was synthesized, at approximately the same concentration level as that of the former, in order to optimize its radiosynthesis, taking advantage from the long half-life of the tritium.

  10. Synthesis of n.c.a. PET-radiotracers with carbon-11

    International Nuclear Information System (INIS)

    Schirbel, A.

    1998-11-01

    Carbon-11 offers the unique possibility of authentic labelling of molecules as radioindicators for non invasive and quantitative determination of physiological functions via positron emission tomography (PET). Therefore, the goal of this thesis was to synthesize of different n.c.a. 11 C-labelled pharmaceuticals for in vivo distribution studies with PET. For the determination of the pharmacokinetics of [1- 11 C]acetate in porcine myocardium during prolonged ischemia, n.c.a. [1- 11 C]acetate was synthesized via carboxylation of methylmagnesium bromide with in target produced n.c.a. [ 11 C]CO 2 with a radiochemical yield (RCY) of 68 ± 7%. The fast (18 min) and reliable radiosynthesis allowed for repeated tracer administration at short intervals ( R c) in humans, [1- 11 C]acetylsalicylic acid, acetyl-[carboxy- 11 C]salicylic acid and [carboxy- 11 C]salicylic acid were prepared. N.c.a. [1- 11 C]acetylsalicylic acid was synthesized via the reaction of [1- 11 C]acetylchloride with salicylic acid salts. The use of the silver salt proved to be superior to the sodium salt and resulted in radiochemical yields of 32 ± 5%. Base-line (clean) separation of the labelled product was achieved using radio-HPLC. With regard to the preparation of n.c.a. [carboxy- 11 C]salicylic acid, several protected and unprotected phenol derivates were metallated and subsequently carboxylated using n.c.a. [ 11 C]CO 2 . Best results (87 ± 3% RCY) could be achieved with 2-(methoxymethoxy)-phenylmagnesium iodide as a precursor and subsequent quantitative cleavage of the MOM-group. Acetylation of n.c.a. [carboxy- 11 C]salicylic acid to acetyl-[carboxy- 11 C]salicylic acid was performed using acetylchloride in CH 2 Cl 2 with a radiochemical yield of 65 ± 4%. (orig.)

  11. Chemical Properties of Dialkyl Halonium Ions (R2Hal+) and Their Neutral Analogues, Methyl Carboranes, CH3-(CHB11Hal11), Where Hal = F, Cl.

    Science.gov (United States)

    Stoyanov, Evgenii S

    2017-04-20

    Chloronium cations in their salts (C n H 2n+1 ) 2 Cl + {CHB 11 Cl 11 - }, with n = 1 to 3 and exceptionally stable carborane anions, are stable at ambient and elevated temperatures. The temperature at which they decompose to carbocations with HCl elimination (below 150 °C) decreases with the increasing n from 1 to 3 because of increasing ionicity of C-Cl bonds in the C-Cl + -C bridge. At room temperature, the salts of cations with n ≥ 4 [starting from t-Bu 2 Cl + or (cyclo-C 5 H 11 ) 2 Cl + ] are unstable and decompose. With decreasing chloronium ion stability, their ability to interact with chloroalkanes to form oligomeric cations increases. It was shown indirectly that unstable salt of fluoronium ions (CH 3 ) 2 F + (CHB 11 F 11 - ) must exist at low temperatures. The proposed (CH 3 ) 2 F + cation is much more reactive than the corresponding chloronium, showing at room temperature chemical properties expected of (CH 3 ) 2 Cl + at elevated temperatures.

  12. [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    International Nuclear Information System (INIS)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars; Guilloteau, Denis; Emond, Patrick

    2003-01-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [ 11 C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [ 11 C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [ 11 C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [ 11 C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [ 11 C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  13. Vibrational spectroscopy investigation using ab initio and density functional theory analysis on the structure of 3-(6-benzoyl-2-oxobenzo[ d]oxazol-3(2 H)-yl)propanoic acid

    Science.gov (United States)

    Arslan, Hakan; Algül, Öztekin; Önkol, Tijen

    2008-08-01

    The molecular structure, vibrational frequencies and infrared intensities of the 3-(6-benzoyl-2-oxobenzo[ d]oxazol-3(2 H)-yl)propanoic acid were calculated by the HF and DFT methods using 6-31G(d) basis set. The FT-infrared spectra have been measured for the title compound in the solid state. We obtained 11 stable conformers for the title compound, however the Conformer 1 is approximately 3.88 kcal/mol more stable than the Conformer 11. The comparison of the theoretical and experimental geometry of the title compound shows that the X-ray parameters fairly well reproduce the geometry of the Conformer 1. The harmonic vibrations computed of this compound by the B3LYP/6-31G(d) method are in a good agreement with the observed IR spectral data. Theoretical vibrational spectra of the title compound were interpreted by means of PEDs using VEDA 4 program.

  14. meso-4,4′-Difluoro-2,2′-{[(3aR,7aS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene}diphenol

    Directory of Open Access Journals (Sweden)

    Augusto Rivera

    2013-02-01

    Full Text Available In the crystal structure of the title compound, C21H24F2N2O2, there are two intramolecular O—H...N hydrogen bonds involving the N atoms of the imidazolidine ring and the hydroxy groups. The crystal studied was a meso compound obtained by the reaction of the aminal (2S,7R,11S,16R-1,8,10,17-tetraazapentacyclo[8.8.1.18,17.02,7.011,16]cosane with 4-fluorophenol. The imidazolidine ring has a twisted conformation with a CH—CH—N—CH2 torsion angle of 44.99 (14° and, surprisingly, the lone pairs of the N atoms are disposed in a syn isomerism, making the title compound an exception to the typical `rabbit-ear effect' in 1,2-diamines. In the crystal, molecules are linked via C—H...F hydrogen bonds, forming chains along the c-axis direction. These chains are linked via another C—H...F hydrogen bond, forming a three-dimensional network.

  15. F/Cl + C2H2 reactions: Are the addition and hydrogen abstraction direct processes?

    International Nuclear Information System (INIS)

    Li Jilai; Geng Caiyun; Huang Xuri; Zhan Jinhui; Sun Chiachung

    2006-01-01

    The reactions of atomic radical F and Cl with acetylene have been studied theoretically using ab initio quantum chemistry methods and transition state theory. The doublet potential energy surfaces were calculated at the CCSD(T)/aug-cc-pVDZ//CCSD/6-31G(d,p), CCSD(T)/aug-cc-pVDZ//UMP2/6-311++G(d,p) and compound method Gaussian-3 levels. Two reaction mechanisms including the addition-elimination and the hydrogen abstraction reaction mechanisms are considered. In the addition-elimination reactions, the halogen atoms approach C 2 H 2 , perpendicular to the C≡C triple bond, forming the pre-reactive complex C1 at the reaction entrance. C1 transforms to intermediate isomer I1 via transition state TSC1/1 with a negative/small barrier for C 2 H 2 F/C 2 H 2 Cl system, which can proceed by further eliminating H atom endothermally. While the hydrogen abstraction reactions also involve C1 for the fluorine atom abstraction of hydrogen, yet the hydrogen abstraction by chlorine atom first forms a collinear hydrogen-bonded complex C2. The other reaction pathways on the doublet PES are less competitive due to thermodynamical or kinetic factors. According to our results, the presence of pre-reactive complexes indicates that the simple hydrogen abstraction and addition in the halogen atoms reaction with unsaturated hydrocarbon should be more complex. Furthermore, based on the analysis of the kinetics of all channels through which the addition and abstraction reactions proceed, we expect that the actual feasibility of the reaction channels may depend on the reaction conditions in the experiment. The present study may be helpful for probing the mechanisms of the title reactions and understanding the halogen chemistry

  16. Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH. I. pH changes measured in states of altered PCO2

    International Nuclear Information System (INIS)

    Buxton, R.B.; Alpert, N.M.; Babikian, V.; Weise, S.; Correia, J.A.; Ackerman, R.H.

    1987-01-01

    The 11 CO 2 method for measuring local brain pH with positron emission tomography (PET) has been experimentally evaluated, testing the adequacy of the kinetic model and the ability of the method to measure changes in brain pH. Plasma and tissue time/activity curves measured during and following continuous inhalation of 11 CO 2 were fit with a kinetic model that includes effects of tissue pH, blood flow, and fixation of CO 2 into compounds other than dissolved gas and bicarbonate ions. For each of ten dogs, brain pH was measured with PET at two values of PaCO 2 (range 21-67 mm Hg). The kinetic model fit the data well during both inhalation and washout of the label, with residual root mean square (RMS) deviations of the model from the measurements consistent with the statistical quality of the PET data. Brain pH calculated from the PET data shows a linear variation with log(PaCO 2 ). These results were in good agreement with previously reported measurements of brain pH, both in absolute value and in variation with PCO 2 . The interpretation of these pH values in normal and pathological states is discussed

  17. On the synthesis of 11C-labelled aromatic amino acids

    International Nuclear Information System (INIS)

    Halldin, C.

    1984-01-01

    The use of 11 C-labelled aromatic amino acids in positron emission tomography (PET) and their importance in physiological studies, especially cerebral protein synthesis or their role as precursors of neurotransmitters, is discussed. The synthesis of 11 -C-labelled aromatic amino acids by various routes is presented and new 11 C-labelled precursors, aromatic and aliphatic 11 C-aldehydes, are reported. The 11 C-aldehydes were obtained in 60-95% radiochemical yield and reaction times were of the order of 5 min. The 11 C-aldehydes have been used in condensation reactions with 2-aryl-5-oxazolones in the presence of a tertiary amine, diazabicyclooctane (DABCO), to produce the corresponding [α- 11 C]-4-arylene-2-aryl-5-oxazolones. Ring opening, hydrogenation and removal of protecting groups were carried out in one step to produce the racemic [3- 11 C]-labelled aromatic amino acids in 8-30% radiochemical yield. The total reaction time was 52-60 min. L-[3- 11 C]Phenylalanine was obtained by a seven-step synthesis in 80% e.e. (enantiomeric excess) and 60% e.e., respectively, in 10-15% radiochemical yield within 60 min, by use of the chiral rhodium complex of (R)-1,2-bis(diphenylphosphino)propane ((R)-PROPHOS) or (+)-2,3-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane ((+)-DIOP) in the hydrogenation reaction. Racemic [2- 11 C]-labelled aromatic amino acids were produced by a high-pressure, high-temperature modification of the Buechere-Strecker synthesis. [2- 11 C]Phenylglycine was obtained in 20% radiochemical yield within 50 min. [3- 11 C]Phenylpyruvic acid was prepared via the aldehyde-oxyzolone condensation reaction in 40% radiochemical yield within 40 min (not including LC separation). Its use in the synthesis of [3- 11 C]-phenylalanine by enzymatic transamination is also discussed. With 32 refs.(Author)

  18. Synthesis and H-1 NMR structural analysis of 11-aryl/heteroarylnaphtha[2,1-b]furans : X-ray crystal structure of 11-(4 '-pyridyl)naphtho[2,1-b]furan

    NARCIS (Netherlands)

    Mashraqui, S.H.; Patil, M.B.; Sangvikar, Y.; Ashraf, M.; Mistry, H.D.; Daub, E.T.H.; Meetsma, A.

    2005-01-01

    Synthesis of biaryl type systems, 11-aryl/heteroarylnaphtho[2,1-b]furans 8-11 has been described with a view to studying the conformational orientation of C-11 aryl/heteroaryl groups. Synthesis of 8-11 was accomplished by a two-step sequence involving O-alkylation of 2-naphthol with appropriate

  19. Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC2-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone.

    Science.gov (United States)

    du Toit, Therina; Bloem, Liezl M; Quanson, Jonathan L; Ehlers, Riaan; Serafin, Antonio M; Swart, Amanda C

    2017-02-01

    Adrenal C 19 steroids serve as precursors to active androgens in the prostate. Androstenedione (A4), 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) are metabolised to potent androgen receptor (AR) agonists, dihydrotestosterone (DHT), 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). The identification of 11OHA4 metabolites, 11KT and 11KDHT, as active androgens has placed a new perspective on adrenal C11-oxy C 19 steroids and their contribution to prostate cancer (PCa). We investigated adrenal androgen metabolism in normal epithelial prostate (PNT2) cells and in androgen-dependent prostate cancer (LNCaP) cells. We also analysed steroid profiles in PCa tissue and plasma, determining the presence of the C 19 steroids and their derivatives using ultra-performance liquid chromatography (UHPLC)- and ultra-performance convergence chromatography tandem mass spectrometry (UPC 2 -MS/MS). In PNT2 cells, sixty percent A4 (60%) was primarily metabolised to 5α-androstanedione (5αDIONE) (40%), testosterone (T) (10%), and androsterone (AST) (10%). T (30%) was primarily metabolised to DHT (10%) while low levels of A4, 5αDIONE and 3αADIOL (≈20%) were detected. Conjugated steroids were not detected and downstream products were present at <0.05μM. Only 20% of 11OHA4 and 11OHT were metabolised with the former yielding 11keto-androstenedione (11KA4), 11KDHT and 11β-hydroxy-5α-androstanedione (11OH-5αDIONE) and the latter yielding 11OHA4, 11KT and 11KDHT with downstream products <0.03μM. In LNCaP cells, A4 (90%) was metabolised to AST-glucuronide via the alternative pathway while T was detected as T-glucuronide with negligible conversion to downstream products. 11OHA4 (80%) and 11OHT (60%) were predominantly metabolised to 11KA4 and 11KT and in both assays more than 50% of 11KT was detected in the unconjugated form. In tissue, we detected C11-oxy C 19 metabolites at significantly higher levels than the C 19 steroids, with

  20. The crystal structure of Cs{sub 2}S{sub 2}O{sub 3}.H{sub 2}O

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, Verena; Schlosser, Marc; Pfitzner, Arno [Regensburg Univ. (Germany). Inst. fuer Anorganische Chemie

    2016-08-01

    A reinvestigation of the alkali metal thiosulfates has led to the new phase Cs{sub 2}S{sub 2}O{sub 3}.H{sub 2}O. At first cesium thiosulfate monohydrate was obtained as a byproduct of the synthesis of Cs{sub 4}In{sub 2}S{sub 5}. Further investigations were carried out using the traditional synthesis reported by J. Meyer and H. Eggeling. Cs{sub 2}S{sub 2}O{sub 3}.H{sub 2}O crystallizes in transparent, colorless needles. The crystal structure of the title compound was determined by single crystal X-ray diffraction at room temperature: space group C2/m (No. 12), unit cell dimensions: a = 11.229(4), b = 5.851(2), c = 11.260(5) Aa, β = 95.89(2) , with Z = 4 and a cell volume of V = 735.9(5) Aa{sup 3}. The positions of all atoms including the hydrogen atoms were located in the structure refinement. Cs{sub 2}S{sub 2}O{sub 3}.H{sub 2}O is isotypic with Rb{sub 2}S{sub 2}O{sub 3}.H{sub 2}O. Isolated tetrahedra [S{sub 2}O{sub 3}]{sup 2-} are coordinated by the alkali metal cations, and in addition they serve as acceptors for hydrogen bonding. For both Cs atoms the shortest distances are observed to oxygen atoms of the S{sub 2}O{sub 3}{sup 2-} anions whereas the terminating sulfur atom has its shortest contacts to the water hydrogen atoms. Thus, an extended hydrogen bonding network is formed. The title compound has also been characterized by IR spectroscopy. IR spectroscopy reveals the vibrational bands of the water molecules at 3385 cm{sup -1}. They show a red shift in the OH stretching and bending modes as compared to free water. This is due both to the S..H hydrogen bonding and to the coordination of H{sub 2}O molecules to the cesium atoms.

  1. (11)C-MK-8278 PET as a tool for pharmacodynamic brain occupancy of histamine 3 receptor inverse agonists.

    Science.gov (United States)

    Van Laere, Koenraad J; Sanabria-Bohórquez, Sandra M; Mozley, David P; Burns, Donald H; Hamill, Terence G; Van Hecken, Anne; De Lepeleire, Inge; Koole, Michel; Bormans, Guy; de Hoon, Jan; Depré, Marleen; Cerchio, Kristine; Plalcza, John; Han, Lingling; Renger, John; Hargreaves, Richard J; Iannone, Robert

    2014-01-01

    The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity. Using PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y). The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further investigated in 15 healthy male volunteers (age, 18-40 y) with up to 3 PET scans and 3 subjects per dose level. The mean effective dose for (11)C-MK-8278 was 5.4 ± 1.1 μSv/MBq. Human brain kinetics showed rapid high uptake and fast washout. Binding potential values can be assessed using the pons as a reference region, with a test-retest repeatability of 7%. Drug RO data showed low interindividual variability per dose (mean RO SD, 2.1%), and a targeted 90% RO can be reached for both IAs at clinically feasible doses. (11)C-MK-8278 is a useful novel PET radioligand for determination of human cerebral H3 receptor binding and allows highly reproducible in vivo brain occupancy of H3-targeting drugs, hereby enabling the evaluation of novel compounds in early development to select doses and schedules.

  2. Crystal structure of (E-3-(2,4-dimethoxyphenyl-1-(1-hydroxynaphthalen-2-ylprop-2-en-1-one

    Directory of Open Access Journals (Sweden)

    Dongsoo Koh

    2014-09-01

    Full Text Available In the title compound, C21H18O4, the C=C bond of the central enone group adopts an E conformation. The dihedral angle formed by the benzene ring and the naphthalene ring system is 6.60 (2°. The methoxy groups on the benzene ring are essentially coplanar with the ring; the C—C—O—C torsion angles being 1.6 (2 and −177.1 (1°. The hydroxy group attached to the naphthalene ring is involved in an intramolecular O—H...O hydrogen bond. The relative conformation of the two double bonds in the enone group is s-cisoid. In the crystal, weak C—H...O hydrogen bonds link the molecules into chains propagating along [010].

  3. Synthesis and preclinical evaluation of [11C]D617, a metabolite of (R)-[11C]verapamil

    NARCIS (Netherlands)

    Verbeek, Joost; Syvänen, Stina; Schuit, Robert C.; Eriksson, Jonas; de Lange, Elizabeth C M; Windhorst, Albert D.; Luurtsema, Gert; Lammertsma, Adriaan A.

    2012-01-01

    OBJECTIVES: (R)-[(11)C]verapamil is widely used as a positron emission tomography (PET) tracer to evaluate P-glycoprotein (P-gp) functionality at the blood-brain barrier in man. A disadvantage of (R)-[(11)C]verapamil is the fact that its main metabolite, [(11)C]D617, also enters the brain. For

  4. Radiosynthesis and in vivo evaluation of a series of substituted {sup 11}C-phenethylamines as 5-HT{sub 2A} agonist PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Ettrup, Anders; Santini, Martin A.; Palner, Mikael; Knudsen, Gitte M. [Copenhagen University Hospital, Neurobiology Research Unit, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Hansen, Martin; Paine, James; Kristensen, Jesper; Begtrup, Mikael [University of Copenhagen, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Gillings, Nic; Herth, Matthias M.; Madsen, Jacob [Copenhagen University Hospital, Rigshospitalet, PET and Cyclotron Unit, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Lehel, Szabolcs [Copenhagen University Hospital, Rigshospitalet, PET and Cyclotron Unit, Copenhagen (Denmark)

    2011-04-15

    Positron emission tomography (PET) imaging of serotonin 2A (5-HT{sub 2A}) receptors with agonist tracers holds promise for the selective labelling of 5-HT{sub 2A} receptors in their high-affinity state. We have previously validated [{sup 11}C]Cimbi-5 and found that it is a 5-HT{sub 2A} receptor agonist PET tracer. In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [{sup 11}C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT{sub 2A} receptor agonist PET tracers in the pig brain. Each radiotracer was injected intravenously into anaesthetized Danish Landrace pigs, and the pigs were subsequently scanned for 90 min in a high-resolution research tomography scanner. To evaluate 5-HT{sub 2A} receptor binding, cortical nondisplaceable binding potentials (BP{sub ND}) were calculated using the simplified reference tissue model with the cerebellum as a reference region. After intravenous injection, all compounds entered the brain and distributed preferentially into the cortical areas, in accordance with the known 5-HT{sub 2A} receptor distribution. The largest target-to-background binding ratio was found for [{sup 11}C]Cimbi-36 which also had a high brain uptake compared to its analogues. The cortical binding of [{sup 11}C]Cimbi-36 was decreased by pretreatment with ketanserin, supporting 5-HT{sub 2A} receptor selectivity in vivo. [{sup 11}C]Cimbi-82 and [{sup 11}C]Cimbi-21 showed lower cortical BP{sub ND}, while [{sup 11}C]Cimbi-27, [{sup 11}C]Cimbi-29, [{sup 11}C]Cimbi-31 and [{sup 11}C]Cimbi-88 gave rise to cortical BP{sub ND} similar to that of [{sup 11}C]Cimbi-5. [{sup 11}C]Cimbi-36 is currently the most promising candidate for investigation of 5-HT{sub 2A} receptor agonist binding in the living human brain with PET. (orig.)

  5. Molecular structure and infrared spectra of the monomeric 3-(methoxy)-1,2-benzisothiazole 1,1-dioxide (methyl pseudosaccharyl ether)

    Science.gov (United States)

    Kaczor, Agnieszka; Almeida, Rui; Gómez-Zavaglia, Andrea; Cristiano, Maria de Lurdes S.; Fausto, Rui

    2008-03-01

    The computational description of saccharin (1,2-benzisothiazol-3(2 H)-one-1,1-dioxide) and its derivatives is difficult due to the presence of hypervalent S dbnd O bonds in their structures. Therefore, in this investigation, the HF, DFT/B3LYP and MP2 methods were used to predict the geometry and the infrared spectrum of the saccharyl derivative 3-(methoxy)-1,2-benzisothiazole 1,1-dioxide (MBID). Their relative predictive capabilities were then evaluated by comparing the obtained results with experimentally available data, namely the newly obtained IR spectra of MBID isolated in low-temperature inert matrices. For each method, different basis sets [6-31++G(d,p), 6-31++G(3df,3pd), 6-311++G(d,p), 6-311++G(2df,2pd), 6-311++G(3df,3pd), aug-cc-pVDZ and aug-cc-pVTZ] were considered. The best overall agreement has been achieved at the B3LYP/6-311++G(3df,3pd) and B3LYP/6-31++G(3df,3pd) levels of theory, showing the adequacy of the B3LYP functional to describe the investigated properties in this type of compounds and stressing the relevance of including high-order polarization functions in the basis set. The chosen level of theory [B3LYP/6-311++G(3df,3pd)] was applied to analyze the vibrational spectra and the geometry of the title molecule. In agreement with the experiment, the C sbnd O sbnd C linkage in MBID is predicted by these calculations to exhibit considerably short (1.320 Å) and long (1.442 Å) (N dbnd )C sbnd O and (H 3)C sbnd O bonds, respectively, and a hybridization of the central oxygen atom close to sp 2 (the C sbnd O sbnd C angle is predicted to be ca. 117°). This C sbnd O sbnd C bonding pattern fits the well-known high reactivity of MBID upon thermal rearrangement, which has been shown to result in easy selective [1,3']-isomerization of the compound.

  6. Test-retest repeatability of myocardial blood flow and infarct size using 11C-acetate micro-PET imaging in mice

    International Nuclear Information System (INIS)

    Croteau, Etienne; Renaud, Jennifer M.; McDonald, Matthew; Klein, Ran; DaSilva, Jean N.; Beanlands, Rob S.B.; DeKemp, Robert A.

    2015-01-01

    Global and regional responses of absolute myocardial blood flow index (iMBF) are used as surrogate markers to assess response to therapies in coronary artery disease. In this study, we assessed the test-retest repeatability of iMBF imaging, and the accuracy of infarct sizing in mice using 11 C-acetate PET. 11 C-Acetate cardiac PET images were acquired in healthy controls, endothelial nitric oxide synthase (eNOS) knockout transgenic mice, and mice after myocardial infarction (MI) to estimate global and regional iMBF, and myocardial infarct size compared to 18 F-FDG PET and ex-vivo histology results. Global test-retest iMBF values had good coefficients of repeatability (CR) in healthy mice, eNOS knockout mice and normally perfused regions in MI mice (CR = 1.6, 2.0 and 1.5 mL/min/g, respectively). Infarct size measured on 11 C-acetate iMBF images was also repeatable (CR = 17 %) and showed a good correlation with the infarct sizes found on 18 F-FDG PET and histopathology (r 2 > 0.77; p < 0.05). 11 C-Acetate micro-PET assessment of iMBF and infarct size is repeatable and suitable for serial investigation of coronary artery disease progression and therapy. (orig.)

  7. Coordination compounds of the nitrate salts of oxycation uranyl (UO22+) and praseodymium(III), neodymium(III) and erbium(III) with 2,2'-bipyridine-1,1'-dioxide

    International Nuclear Information System (INIS)

    Madan, S.; Chan, K.S.

    1977-01-01

    Coordination compounds with 2,2'-bipyridine-1,1'-dioxide (bipyO 2 ) having the composition [UO 2 (bipyO 2 ) 2 (NO 3 ) 2 ].4H 2 O, [Pr(bipyO 2 ) 4 (NO 3 ) 2 ]NO 3 .2H 2 O, [Dy(bipyO 2 ) 4 (NO 3 ) 2 ]NO 3 .4H 2 O and [Er(bipyO 2 ) 4 (NO 3 ) 2 ]NO 3 .4H 2 O have been synthesized. These new complexes have been characterized by electrical conductance, X-ray powder patterns and IR spectral measurements. (author)

  8. Crystal structure of methyl 2-(2H-1,3-benzodioxol-5-yl-7,9-dibromo-8-oxo-1-oxaspiro[4.5]deca-2,6,9-triene-3-carboxylate

    Directory of Open Access Journals (Sweden)

    Lucimara Julio Martins

    2014-12-01

    Full Text Available The title compound, C18H12Br2O6, was synthesized from Morita–Baylis–Hillman adducts. It incorporates the brominated spiro-hexadienone moiety typically exhibited by compounds of this class that exhibit biological activity. Both the brominated cyclohexadienone and the central five-membered rings are nearly planar (r.m.s. deviations of 0.044 and 0.016 Å, respectively, being almost perpendicularly oriented [interplanar angle = 89.47 (5°]. With respect to the central five-membered ring, the brominated cyclohexadienone ring, the benzodioxol ring and the carboxylate fragment make C—O—C—C, O—C—C—C and C—C—C—O dihedral angles of −122.11 (8, −27.20 (11 and −8.40 (12°, respectively. An intramolecular C—H...O hydrogen bond occurs. In the crystal, molecules are linked by non-classical C—H...O and C—H...Br hydrogen bonds resulting in a molecular packing in which the brominated rings are in a head-to-head orientation, forming well marked planes parallel to the b axis.

  9. Structurally characterized 1,1,3,3-tetramethylguanidine solvated magnesium aryloxide complexes: [Mg(mu-OEt)(DBP)(H-TMG)]2, [Mg(mu-OBc)(DBP)(H-TMG)]2, [Mg(mu-TMBA)(DBP)(H-TMG)]2, [Mg(mu-DPP)(DBP)(H-TMG)]2, [Mg(BMP)2(H-TMG)2], [Mg(O-2,6-Ph2C6H3)2 (H-TMG)2].

    Science.gov (United States)

    Monegan, Jessie D; Bunge, Scott D

    2009-04-06

    The synthesis and structural characterization of several 1,1,3,3-tetramethylguanidine (H-TMG) solvated magnesium aryloxide complexes are reported. Bu(2)Mg was successfully reacted with H-TMG, HOC(6)H(3)(CMe(3))(2)-2,6 (H-DBP), and either ethanol, a carboxylic acid, or diphenyl phosphate in a 1:1 ratio to yield the corresponding [Mg(mu-L)(DBP)(H-TMG)](2) where L = OCH(2)CH(3) (OEt, 1), O(2)CC(CH(3))(3) (OBc, 2), O(2)C(C(6)H(2)-2,4,6-(CH(3))(3)) (TMBA, 3), or O(2)P(OC(6)H(5))(2) (DPP, 4). Bu(2)Mg was also reacted with two equivalents of H-TMG and HOC(6)H(3)(CMe(3))-2-(CH(3))-6 (BMP) or HO-2,6-Ph(2)C(6)H(3) to yield [Mg(BMP)(2)(H-TMG)(2)] (5) and [Mg(O-2,6-Ph(2)C(6)H(3))(2)(H-TMG)(2)] (6). Compounds 1-6 were characterized by single-crystal X-ray diffraction. Polymerization of l- and rac-lactide with 1 was found to generate polylactide (PLA). A discussion concerning the relevance of compounds 2 - 4 to the structure of Mg-activated phosphatase enzymes is also provided. The bulk powders for all complexes were found to be in agreement with the crystal structures based on elemental analyses, FT-IR spectroscopy, and (1)H, (13)C and (31)P NMR studies.

  10. Carbon-11 labelled ketamine-synthesis, distribution in mice and PET studies in baboons

    International Nuclear Information System (INIS)

    Shiue, C.-Y.; Vallabhahosula, Shankar; Wolf, Alfred P.; Dewey, Stephen L.; Fowler, Joanna S.; Schlyer, David J.; Arnett, Carroll D.; Zhou Yiguo

    1997-01-01

    No-carrier-added (NCA)[ 11 C](±)-ketamine (2a) and its enantiomers (+)-2b and (-)-2c were synthesized by methylation of the corresponding norketamine (1a-c) with [ 11 C]H 3 I in an overall radiochemical yield of 20% (EOB) with specific activities of 0.35-0.45 Ci/μmole at EOB in a synthesis time of 40 min from EOB. Compound 2a was metabolized rapidly in mouse brain and labeled metabolites appeared in baboon plasma. PET studies of compounds 2a-c in a baboon showed that influx of compounds 2a-c into the brain was high for the first few min but radioactivity then declined rapidly. Although the retention of radioactivity in the baboon striatum was not significantly different for 2a-c 20 min post-injection, graphical analysis of time-activity data for each enantiomer and for the racemate in baboon striatum suggested that (+)-ketamine may interact with receptors slightly more effectively than its (-)-enantiomer or racemate. However, due to its rapid metabolism in the brain and a similar uptake in the striatum and cerebellum, [ 11 C]ketamine may not be an ideal tracer for studying NMDA receptor with PET

  11. Bis[2-(2-aminoethyl-1H-benzimidazole-κ2N2,N3](nitrato-κ2O,O′cobalt(II chloride trihydrate

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    2012-06-01

    Full Text Available In the title compound, [Co(NO3(C9H11N32]Cl·3H2O, the CoII atom is coordinated by four N atoms from two chelating 2-(2-aminoethyl-1H-benzimidazole ligands and two O atoms from one nitrate anion in a distorted octahedral coordination environment. In the crystal, N—H...Cl, N—H...O, O—H...Cl and O—H...O hydrogen bonds link the complex cations, chloride anions and solvent water molecules into a three-dimensional network. π–π interactions between the imidazole and benzene rings and between the benzene rings are observed [centroid–centroid distances = 3.903 (3, 3.720 (3, 3.774 (3 and 3.926 (3 Å].

  12. Synthesis, Biodistribution and In vitro Evaluation of Brain Permeable High Affinity Type 2 Cannabinoid Receptor Agonists [11C]MA2 and [18F]MA3.

    Science.gov (United States)

    Ahamed, Muneer; van Veghel, Daisy; Ullmer, Christoph; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy M

    2016-01-01

    The type 2 cannabinoid receptor (CB2) is a member of the endocannabinoid system and is known for its important role in (neuro)inflammation. A PET-imaging agent that allows in vivo visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and in vitro evaluation of a carbon-11 ([ 11 C]MA2) and a fluorine-18 ([ 18 F]MA3) labeled analog of a highly potent N -arylamide oxadiazole CB2 agonist (EC 50 = 0.015 nM). MA2 and MA3 behaved as potent CB2 agonist (EC 50 : 3 nM and 0.1 nM, respectively) and their in vitro binding affinity for h CB2 was found to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl group) was found to have higher binding affinity and EC 50 values when compared to the originally reported trifluoromethyl analog 12 . [ 11 C]MA2 and [ 18 F]MA3 were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [ 11 C]MA2 and [ 18 F]MA3 are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for in vivo imaging of brain CB2 receptors. However, in view of its higher affinity and selectivity, further detailed evaluation of MA3 as a PET tracer for CB2 is warranted.

  13. Experimental and semi-empirical and DFT calculational studies on (e)-2-(1-(2-(4-methylphenylsulfonamido) ethyliminio) ethyl) phenolate

    International Nuclear Information System (INIS)

    Alpaslan, G.; Agar, E.; Ersahin, F.; Isik, S.; Erdoenmez, A.

    2010-01-01

    The molecular and crystal structure of the title compound, C 1 7H 2 0N 2 O 3 S, has been determined by X-ray single crystal diffraction technique. The compound crystallizes in the monoclinic, space group P2 1 /n with unit cell dimensions a=11.4472(6), b=11.1176(4), c=13.4873(7)A 0 , M r =332.41, V=1639.36(13)A 03 , Z=4, R 1 =0.034 and wR 2 =0.097. The molecule adopts a zwitterionic form, stabilized by an intramolecular N + -H 2 O - type ionic weak hydrogen bond. The molecule pack via intermolecular N-H 2 O hydrogen bonds which, together with an intramolecular N + -H 2 O - bond, form an S(6)R 2 4 (4)S(6) motif. Calculational studies were performed by using AM1, PM3 semi-empirical and DFT methods. Geometry optimizations of compound have been carried out by using three semi-empirical methods and DFT method and bond lengths, bond and torsion angles of title compound have been determined. Atomic charge distribution have been obtained from AM1, PM3 and DFT. In order to determine conformational flexibility on the molecule, molecular energy profile of the title compound was obtained with respect to the selected torsion angle T(N1-C9-C10-N2), which is varied from -180 degrees to +180 degrees in every 10 via PM3 semi-empirical method.

  14. Radiosynthesis of (S)-5-methoxymethyl-3- 6-(4,4,4-trifluoro-butoxy)benzo dis-oxazol-3-yl ox azolidin-2- C-11 one (C-11 SL25.1188), a novel radioligand for imaging monoamine oxidase-B with PET

    International Nuclear Information System (INIS)

    Bramoulle, Y.; Saba, W.; Valette, H.; Bottlaender, M.; Dolle, F.; Puech, F.; George, P.

    2008-01-01

    Within a novel series of 2-oxazolidinones developed in the past by Sanofi-Synthelabo, SL25.1188 ((S)-5-methoxymethyl-3-[6-(4,4,4-trifluoro-butoxy)benzo[d]isoxazol-3-yl]o xazolidin-2-one), a compound that inhibits selectively and competitively MAO-B in human and rat brain (Ki values of 2.9 and 8.5 nM for MAO-B, respectively, and ED 50 (rat): 0.6 mg/kg p.o.), was considered an appropriate candidate for imaging this enzyme with positron emission tomography.SL25.1188 was labelled with carbon-11 (T 1/2 : 20.38 min) in one chemical step using the following process: (i) reaction of [ 11 C]phosgene with the corresponding ring-opened precursor (1.2-2.5 mg) at 100 degrees C for 2 min in dichloromethane (0.5 ml) followed by (ii) concentration to dryness of the reaction mixture and finally (iii) semi-preparative HPLC purification on a Waters Symmetry (R) C18. A total of 300-500 MBq of [ 11 C]SL25.1188 (≥95% chemically and radiochemically pure) could be obtained within 30-32 min (Sep-pak-based formulation included) with specific radioactivities ranging from 50 to 70 GBq/μmol (3.5-7% decay-corrected radiochemical yield, based on starting [ 11 C]CH 4 ). (authors)

  15. Radiosynthesis of (S)-5-methoxymethyl-3- 6-(4,4,4-trifluoro-butoxy)benzo dis-oxazol-3-yl ox azolidin-2- C-11 one (C-11 SL25.1188), a novel radioligand for imaging monoamine oxidase-B with PET

    Energy Technology Data Exchange (ETDEWEB)

    Bramoulle, Y.; Saba, W.; Valette, H.; Bottlaender, M.; Dolle, F. [CEA, Serv Hosp Frederic Joliot, Inst dImagerie BioMed, F-91401 Orsay (France); Puech, F.; George, P. [Sanofi Aventis, F-92200 Bagneux (France)

    2008-07-01

    Within a novel series of 2-oxazolidinones developed in the past by Sanofi-Synthelabo, SL25.1188 ((S)-5-methoxymethyl-3-[6-(4,4,4-trifluoro-butoxy)benzo[d]isoxazol-3-yl]o xazolidin-2-one), a compound that inhibits selectively and competitively MAO-B in human and rat brain (Ki values of 2.9 and 8.5 nM for MAO-B, respectively, and ED{sub 50} (rat): 0.6 mg/kg p.o.), was considered an appropriate candidate for imaging this enzyme with positron emission tomography.SL25.1188 was labelled with carbon-11 (T{sub 1/2}: 20.38 min) in one chemical step using the following process: (i) reaction of [{sup 11}C]phosgene with the corresponding ring-opened precursor (1.2-2.5 mg) at 100 degrees C for 2 min in dichloromethane (0.5 ml) followed by (ii) concentration to dryness of the reaction mixture and finally (iii) semi-preparative HPLC purification on a Waters Symmetry (R) C18. A total of 300-500 MBq of [{sup 11}C]SL25.1188 ({>=}95% chemically and radiochemically pure) could be obtained within 30-32 min (Sep-pak-based formulation included) with specific radioactivities ranging from 50 to 70 GBq/{mu}mol (3.5-7% decay-corrected radiochemical yield, based on starting [{sup 11}C]CH{sub 4}). (authors)

  16. 2,2′-{1,1′-[Butane-1,4-diylbis(oxynitrilo]diethylidyne}di-1-naphthol

    Directory of Open Access Journals (Sweden)

    Wen-Kui Dong

    2009-06-01

    Full Text Available The title compound, C28H28N2O4, was synthesized by the reaction of 2-acetyl-1-naphthol with 1,4-bis(aminooxybutane in ethanol. The molecule, which lies about an inversion centre, adopts a linear structure, in which the oxime groups and naphthalene ring systems assume an anti conformation. The intramolecular interplanar distance between parallel naphthalene rings is 1.054 (3 Å. Intramolecular O—H...N hydrogen bonds are formed between the oxime nitrogen and hydroxy groups.

  17. Synthesis and Molecular Structure of 6-Amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H-one

    Directory of Open Access Journals (Sweden)

    Gene-Hsiang Lee

    2006-03-01

    Full Text Available The title compound 6-amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]-triazin-8(7H-one (4, molecular formula C11H10N6OS, was obtained by the reaction of3-amino-2-benzyl-6-hydrazino-1,2,4-triazin-5(2H-one (3 with carbon disulfide in awater/pyridine mixture. Compound 4 can also be synthesized by reacting6-amino-3(2Hmercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H-one (7 with benzylbromide in methanolic ammonia water. The compound crystallizes in the monoclinicspace group P21/c with a = 7.2926(15, b = 14.456(2, c = 11.436(2 å, β = 105.30(2°, V= 1162.9(4 å3 and Z = 4, resulting in a density Dcalc of 1.567 g/cm3. Molecules of 4 arelinked by extensive intermolecular N-H···N and N-H···O hydrogen bonding [graph set R22 (9]. The structure is further stabilized by π-π stacking interactions. 2

  18. Mapping a2 Adrenoceptors of the Human Brain with 11C-Yohimbine

    DEFF Research Database (Denmark)

    Nahimi, Adjmal; Jakobsen, Steen; Munk, Ole

    2015-01-01

    A previous study from this laboratory suggested that 11C-yohimbine, a selective α2-adrenoceptor antagonist, is an appropriate ligand for PET of α2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood–brain...... values of VT ranged from 0.82 mL cm−3 in the right frontal cortex to 0.46 mL cm−3 in the corpus callosum, with intermediate VT values in subcortical structures. Binding potentials averaged 0.6–0.8 in the cortex and 0.2–0.5 in subcortical regions. Conclusion: The maps of 11C-yohimbine binding to α2...... adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer 11C-yohimbine for mapping α2 adrenoceptors in human brain in vivo....

  19. Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11.

    Science.gov (United States)

    Morici, Paola; Fais, Roberta; Rizzato, Cosmeri; Tavanti, Arianna; Lupetti, Antonella

    2016-01-01

    The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP) was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans.

  20. Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11

    Science.gov (United States)

    Morici, Paola; Fais, Roberta; Rizzato, Cosmeri

    2016-01-01

    The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP) was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans. PMID:27902776

  1. Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11.

    Directory of Open Access Journals (Sweden)

    Paola Morici

    Full Text Available The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans.

  2. trans-Bis(perchlorato-κOtetrakis(1H-pyrazole-κN2copper(II

    Directory of Open Access Journals (Sweden)

    Viktor Zapol'skii

    2008-10-01

    Full Text Available The title compound, [Cu(ClO42(C3H4N24], was obtained unexpectedly by the reaction of copper(II perchlorate hexahydrate with equimolar amounts of 1-chloro-1-nitro-2,2,2-tripyrazolylethane in methanol solution. The crystal structure comprises octahedrally coordinated Cu2+ ions, located on an inversion centre, with four pyrazole ligands in the equatorial plane. The average Cu—N distance is 2.000 (1 Å. Two perchlorate ions are coordinated to copper in trans positions [Cu—O = 2.4163 (11 Å].

  3. Structure elucidation of 3-[1-(6-methoxy-2-naphtyl)ethyl]-6-(2,4-dichlorophenyl)-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine, C23H18Cl2N4OS from synchrotron X-ray powder diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Gündoğdu, Gülsüm; Aytaç, Sevim Peri; Müller, Melanie; Tozkoparan, Birsen; Kaynak, Filiz Betül

    2017-12-01

    The 3-[1-(6-methoxy-2-naphtyl)ethyl]-6-(2,4-dichlorophenyl)-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine, C23H18Cl2N4OS compound was synthesized, as a member of the family of novel potential anticancer agents. The structure of the title compound was characterized by IR,1H-NMR, mass spectroscopy, and elemental analysis, previously. In this study, the crystal structure of this compound has been determined from synchrotron X-ray powder diffraction data. The crystal structure was solved by simulated annealing and the final structure was achieved by Rietveld refinement method using soft restrains on all interatomic bond lengths and angles. This compound crystallizes in space groupP21,Z= 2, with the unit-cell parametersa= 15.55645(11) Å,b= 8.61693(6) Å,c= 8.56702(6) Å,β= 104.3270(4)°, andV= 1112.68(1) Å3. In the crystal structure, strong C-H∙∙∙πand weak intermolecular hydrogen-bonding interactions link the molecules into a three-dimensional network. The molecules are in a head-to-head arrangement in the unit cell.

  4. PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [{sup 11}C]MeDAS, [{sup 11}C]CIC and [{sup 11}C]PIB

    Energy Technology Data Exchange (ETDEWEB)

    Paula Faria, Daniele de [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, Department of Neuroscience, Groningen (Netherlands); University of Sao Paulo Medical School, Center of Nuclear Medicine, Sao Paulo (Brazil); Copray, Sjef [University of Groningen, University Medical Center Groningen, Department of Neuroscience, Groningen (Netherlands); Sijbesma, Jurgen W.A.; Willemsen, Antoon T.M.; Dierckx, Rudi A.J.O.; Vries, Erik F.J. de [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Buchpiguel, Carlos A. [University of Sao Paulo Medical School, Center of Nuclear Medicine, Sao Paulo (Brazil)

    2014-05-15

    In this study, we compared the ability of [{sup 11}C]CIC, [{sup 11}C]MeDAS and [{sup 11}C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake. Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group). The kinetics of [{sup 11}C]CIC, [{sup 11}C]MeDAS and [{sup 11}C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [{sup 11}C]CIC make this tracer less suitable for in vivo PET imaging. [{sup 11}C]PIB showed good uptake in the white matter in the cerebrum, but [{sup 11}C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [{sup 11}C]MeDAS distribution correlated well with myelin density in different brain regions. This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [{sup 11}C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [{sup 11}C]CIC and [{sup 11}C]PIB. (orig.)

  5. [{sup 11}C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 17176, Stockholm (Sweden); Guilloteau, Denis; Emond, Patrick [INSERM U316 Universite Francois Rabelais, Tours (France)

    2003-09-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2{beta}-carbomethoxy-3{beta}-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [{sup 11}C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/{mu}mol). [{sup 11}C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled {beta}-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [{sup 11}C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [{sup 11}C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [{sup 11}C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  6. N-[7-Ethoxy-1-(prop-2-en-1-yl-1H-indazol-4-yl]-4-methylbenzenesulfonamide

    Directory of Open Access Journals (Sweden)

    Najat Abbassi

    2011-07-01

    Full Text Available In the title compound, C19H21N3O3S, the C—SO2—NH—C torsion angle is 103.72 (11°. The almost planar indazole ring [r.m.s. deviation = 0.0202 (14 Å] is twisted away from the methylbenzene ring by 76.87 (7°. The vinyl group is disordered over two orientations with site occupancies of 0.622 (10 and 0.378 (10. The S atom has a distorted tetrahedral geometry [maximum deviation: O—S—O = 119.18 (11°]. An intramolecular C—H...O hydrogen bond occurs. In the crystal, two molecules are linked about a center of inversion by pairs of N—H...O hydrogen bonds, generating a dimer. C—H...π interactions are also observed.

  7. Evaluation of clinial usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging

    International Nuclear Information System (INIS)

    Enomoto, Kazuo; Matsui, Yoshifumi; Okazumi, Shinichi

    1994-01-01

    We studied 11 C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11 C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3 H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection of 11 C-MET, the increase in rate of radioactivity of 11 C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11 C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates. (author)

  8. Radiosynthesis and radiopharmacological evaluation of [N-methyl-11C]Org 34850 as a glucocorticoid receptor (GR)-binding radiotracer

    International Nuclear Information System (INIS)

    Wuest, Frank; Kniess, Torsten; Henry, Brian; Peeters, Bernardus W.M.M.; Wiegerinck, Peter H.G.; Pietzsch, Jens; Bergmann, Ralf

    2009-01-01

    The radiosynthesis of [N-methyl- 11 C]Org 34850 as a potential brain glucocorticoid receptor (GR)-binding radiotracer is described. The radiosynthesis was accomplished via N-methylation of the corresponding desmethyl precursor with [ 11 C]methyl triflate in a remotely controlled synthesis module to give the desired compound in a radiochemical yield of 23±5% (decay-corrected, based upon [ 11 C]CO 2 ) at a specific activity of 47±12 GBq/μmol (n=15) at the end-of-synthesis (EOS). The radiochemical purity after semi-preparative HPLC purification exceeded 95%. The total synthesis time was 35-40 min after end-of-bombardment (EOB). The radiotracer is rapidly metabolized in rat plasma leading to the formation of two more hydrophilic metabolites as the major metabolites. Radiopharmacological evaluation involving biodistribution and small animal PET imaging in normal Wistar rats showed that the compound [N-methyl- 11 C]Org 34850 is not able to sufficiently penetrate the blood-brain barrier. Therefore, compound [N-methyl- 11 C]Org 34850 seems not to be a suitable PET radiotracer for imaging rat brain GRs. However, involvement of Pgp or species differences requires further clarification to establish whether the radiotracer [N-methyl- 11 C]Org 34850 may still represent a suitable candidate for imaging GRs in humans

  9. Radiosynthesis and radiopharmacological evaluation of [N-methyl-11C]Org 34850 as a glucocorticoid receptor (GR)-binding radiotracer.

    Science.gov (United States)

    Wuest, Frank; Kniess, Torsten; Henry, Brian; Peeters, Bernardus W M M; Wiegerinck, Peter H G; Pietzsch, Jens; Bergmann, Ralf

    2009-02-01

    The radiosynthesis of [N-methyl-(11)C]Org 34850 as a potential brain glucocorticoid receptor (GR)-binding radiotracer is described. The radiosynthesis was accomplished via N-methylation of the corresponding desmethyl precursor with [(11)C]methyl triflate in a remotely controlled synthesis module to give the desired compound in a radiochemical yield of 23+/-5% (decay-corrected, based upon [(11)C]CO(2)) at a specific activity of 47+/-12 GBq/micromol (n=15) at the end-of-synthesis (EOS). The radiochemical purity after semi-preparative HPLC purification exceeded 95%. The total synthesis time was 35-40 min after end-of-bombardment (EOB). The radiotracer is rapidly metabolized in rat plasma leading to the formation of two more hydrophilic metabolites as the major metabolites. Radiopharmacological evaluation involving biodistribution and small animal PET imaging in normal Wistar rats showed that the compound [N-methyl-(11)C]Org 34850 is not able to sufficiently penetrate the blood-brain barrier. Therefore, compound [N-methyl-(11)C]Org 34850 seems not to be a suitable PET radiotracer for imaging rat brain GRs. However, involvement of Pgp or species differences requires further clarification to establish whether the radiotracer [N-methyl-(11)C]Org 34850 may still represent a suitable candidate for imaging GRs in humans.

  10. Radiosynthesis and in vivo evaluation of N-[11C]methylated imidazopyridineacetamides as PET tracers for peripheral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Sekimata, Katsuhiko; Hatano, Kentaro; Ogawa, Mikako; Abe, Junichiro; Magata, Yasuhiro; Biggio, Giovanni; Serra, Mariangela; Laquintana, Valentino; Denora, Nunzio; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano; Ito, Kengo

    2008-01-01

    Imidazopyridineacetoamide 5-8, a series of novel and potentially selective peripheral benzodiazepine receptor (PBR) ligands with affinities comparable to those of known PBR ligands, was investigated. Radiosyntheses of [ 11 C]5, 6, 7 or 8 was accomplished by N-methylation of the corresponding desmethyl precursors with [ 11 C]methyl iodide in the presence of NaH in dimethylformamide (DMF), resulting in 25% to 77% radiochemical yield and specific activitiy of 20 to 150 MBq/nmol. Each of the labeled compounds was injected in ddY mice, and the radioactivity and weight of dissected peripheral organs and brain regions were measured. Organ distribution of [ 11 C]7 was consistent with the known PBR distribution. Moreover, [ 11 C]7 showed the best combination of brain uptake and PBR binding, leading to its high retention in the olfactory bulb and cerebellum, areas where PBR density is high in mouse brain. Coinjection of PK11195 or unlabeled 7 significantly reduced the brain uptake of [ 11 C]7. These results suggest that [ 11 C]7 could be a useful radioligand for positron emission tomography imaging of PBRs

  11. Crystal structure of 3-{5-[3-(4-fluorophenyl-1-isopropyl-1H-indol-2-yl]-1H-pyrazol-1-yl}indolin-2-one ethanol monosolvate

    Directory of Open Access Journals (Sweden)

    Md. Lutfor Rahman

    2016-03-01

    Full Text Available The title indolin-2-one compound, C28H23FN4O·C2H6O, crystallizes as a 1:1 ethanol solvate. The ethanol molecule is disordered over two positions with refined site occupancies of 0.560 (14 and 0.440 (14. The pyrazole ring makes dihedral angles of 84.16 (10 and 85.33 (9° with the indolin-2-one and indole rings, respectively, whereas the dihedral angle between indolin-2-one and indole rings is 57.30 (7°. In the crystal, the components are linked by N—H...O and O—H...O hydrogen bonds, forming an inversion molecule–solvate 2:2 dimer with R44(12 ring motifs. The crystal structure is consolidated by π–π interaction between pairs of inversion-related indolin-2-one rings [interplanar spacing = 3.599 (2 Å].

  12. Magnetic measurements and neutron diffraction study of the layered hybrid compounds Mn(C8H4O4)(H2O)2 and Mn2(OH)2(C8H4O4)

    International Nuclear Information System (INIS)

    Sibille, Romain; Mesbah, Adel; Mazet, Thomas; Malaman, Bernard; Capelli, Silvia; François, Michel

    2012-01-01

    Mn(C 8 H 4 O 4 )(H 2 O) 2 and Mn 2 (OH) 2 (C 8 H 4 O 4 ) layered organic–inorganic compounds based on manganese(II) and terephthalate molecules (C 8 H 4 O 4 2− ) have been studied by DC and AC magnetic measurements and powder neutron diffraction. The dihydrated compound behaves as a 3D antiferromagnet below 6.5 K. The temperature dependence of its χT product is typical of a 2D Heisenberg system and allows determining the in-plane exchange constant J≈−7.4 K through the carboxylate bridges. The magnetic structure confirms the in-plane nearest neighbor antiferromagnetic interactions and the 3D ordering. The hydroxide based compound also orders as a 3D antiferromagnet with a higher Néel temperature (38.5 K). Its magnetic structure is described from two antiferromagnetically coupled ferromagnetic sublattices, in relation with the two independent metallic sites. The isothermal magnetization data at 2 K are consistent with the antiferromagnetic ground-state of these compounds. However, in both cases, a slope change points to field-induced modification of the magnetic structure. - Graphical abstract: The macroscopic magnetic properties and magnetic structures of two metal-organic frameworks based on manganese (II) and terephthalate molecules are presented. Highlights: ► Magnetic study of Mn(C 8 H 4 O 4 )(H 2 O) 2 and Mn 2 (OH) 2 (C 8 H 4 O 4 ). ► Two compounds with common features (interlayer linker/distance, S=5/2 spin). ► Magnetic measurements quantitatively analyzed to deduce exchange constants. ► Magnetic structures determined from neutron powder diffraction experiments.

  13. Reproducibility of repeated measures of deuterium substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) binding in the human brain

    International Nuclear Information System (INIS)

    Logan, Jean; Fowler, Joanna S.; Volkow, Nora D.; Wang, Gene-Jack; MacGregor, Robert R.; Shea, Colleen

    2000-01-01

    The purpose of this study was to assess the reproducibility of repeated positron emission tomography (PET) measures of brain monoamine oxidase B (MAO B) using deuterium-substituted [ 11 C]L-deprenyl ([ 11 C]L-deprenyl-D2) in normal subjects and to validate the method used for estimating the kinetic constants from the irreversible 3-compartment model applied to the tracer binding. Five normal healthy subjects (age range 23-73 years) each received two PET scans with [ 11 C]L-deprenyl-D2. The time interval between scans was 7-27 days. Time-activity data from eight regions of interest and an arterial plasma input function was used to calculate λk 3 , a model term proportional to MAO B, and K 1 , the plasma to brain transfer constant that is related to blood flow. Linear (LIN) and nonlinear least-squares (NLLSQ) estimation methods were used to calculate the optimum model constants. A comparison of time-activity curves for scan 1 and scan 2 showed that the percent of change for peak uptake varied from -18.5 to 15.0% and that increases and decreases in uptake on scan 2 were associated with increases and decreases in the value of the arterial input of the tracer. Calculation of λk 3 showed a difference between scan 1 and scan 2 in the global value ranging between -6.97 and 4.5% (average -2.1±4.7%). The average percent change for eight brain regions for the five subjects was -2.84±7.07%. Values of λk 3 for scan 1 and scan 2 were highly correlated (r 2 =0.98; p 1 showed a significant correlation between scan 1 and scan 2 (r 2 =0.61; p 11 C]L-deprenyl-D2 varied between scan 1 and scan 2, driven by the differences in arterial tracer input. Application of a 3-compartment model to regional time-activity data and arterial input function yielded λk 3 values for scan 1 and scan 2 with an average difference of -2.84 ± 7.07%. Linear regression applied to values of λk 3 from the LIN and NLLSQ methods validated the use of the linear method for calculating λk 3

  14. One carbon metabolism in SAR11 pelagic marine bacteria.

    Directory of Open Access Journals (Sweden)

    Jing Sun

    Full Text Available The SAR11 Alphaproteobacteria are the most abundant heterotrophs in the oceans and are believed to play a major role in mineralizing marine dissolved organic carbon. Their genomes are among the smallest known for free-living heterotrophic cells, raising questions about how they successfully utilize complex organic matter with a limited metabolic repertoire. Here we show that conserved genes in SAR11 subgroup Ia (Candidatus Pelagibacter ubique genomes encode pathways for the oxidation of a variety of one-carbon compounds and methyl functional groups from methylated compounds. These pathways were predicted to produce energy by tetrahydrofolate (THF-mediated oxidation, but not to support the net assimilation of biomass from C1 compounds. Measurements of cellular ATP content and the oxidation of (14C-labeled compounds to (14CO(2 indicated that methanol, formaldehyde, methylamine, and methyl groups from glycine betaine (GBT, trimethylamine (TMA, trimethylamine N-oxide (TMAO, and dimethylsulfoniopropionate (DMSP were oxidized by axenic cultures of the SAR11 strain Ca. P. ubique HTCC1062. Analyses of metagenomic data showed that genes for C1 metabolism occur at a high frequency in natural SAR11 populations. In short term incubations, natural communities of Sargasso Sea microbial plankton expressed a potential for the oxidation of (14C-labeled formate, formaldehyde, methanol and TMAO that was similar to cultured SAR11 cells and, like cultured SAR11 cells, incorporated a much larger percentage of pyruvate and glucose (27-35% than of C1 compounds (2-6% into biomass. Collectively, these genomic, cellular and environmental data show a surprising capacity for demethylation and C1 oxidation in SAR11 cultures and in natural microbial communities dominated by SAR11, and support the conclusion that C1 oxidation might be a significant conduit by which dissolved organic carbon is recycled to CO(2 in the upper ocean.

  15. N-(2,6-Dimethyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl-2-hydroxy-2,2-diphenylacetamide

    Directory of Open Access Journals (Sweden)

    Eser Ihan

    2008-10-01

    Full Text Available In the title compound, C24H28N2O3S, the pendant methyl C atom bonded to the cyclohexane ring is disordered over two sites in a 0.580 (11:0.420 (11 ratio. The cyclohexane ring adopts a distorted chair conformation while the thiazolidine ring has an envelope conformation. The two phenyl rings make a dihedral angle of 71.8 (2° with each other. The conformation is stabilized by an intramolecular N—H...O hydrogen bond. In the crystal structure, an intermolecular hydrogen bond O—H...O occurs.

  16. Strategy for improved [11C]DAA1106 radiosynthesis and in vivo peripheral benzodiazepine receptor imaging using microPET, evaluation of [11C]DAA1106

    International Nuclear Information System (INIS)

    Probst, Katrin C.; Izquierdo, David; Bird, Joseph L.E.; Brichard, Laurent; Franck, Dominic; Davies, John R.; Fryer, Tim D.; Richards, Hugh K.; Clark, John C.; Davenport, Anthony P.; Weissberg, Peter L.; Warburton, Elizabeth A.

    2007-01-01

    Introduction: The peripheral benzodiazepine receptor (PBR) has shown considerable potential as a clinical marker of neuroinflammation and tumour progression. [ 11 C]DAA1106 ([ 11 C]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)-acetamide) is a promising positron emission tomography (PET) radioligand for imaging PBRs. Methods: A four-step synthetic route was devised to prepare DAA1123, the precursor for [ 11 C]DAA1106. Two robust, high yielding methods for radiosynthesis based on [ 11 C]-O-methylation of DAA1123 were developed and implemented on a nuclear interface methylation module, producing [ 11 C]DAA1106 with up to 25% radiochemical yields at end-of-synthesis based on [ 11 C]CH 3 I trapped. Evaluation of [ 11 C]DAA1106 for in vivo imaging was performed in a rabbit model with microPET, and the presence of PBR receptor in the target organ was further corroborated by immunohistochemistry. Results: The standard solution method produced 2.6-5.2 GBq (n=19) of [ 11 C]DAA1106, whilst the captive solvent method produced 1.6-6.3 GBq (n=10) of [ 11 C]DAA1106. Radiochemical purities obtained were 99% and specific radioactivity at end-of-synthesis was up to 200 GBq/μmol for both methods. Based on radiochemical product, shorter preparation times and simplicity of synthesis, the captive solvent method was chosen for routine productions of [ 11 C]DAA1106. In vivo microPET [ 11 C]DAA1106 scans of rabbit kidney demonstrated high levels of binding in the cortex. The subsequent introduction of nonradioactive DAA1106 (0.2 μmol) produced considerable displacement of the radioactive signal in this region. The presence of PBR in kidney cortex was further corroborated by immunohistochemistry. Conclusions: A robust, high yielding captive solvent method of [ 11 C]DAA1106 production was developed which enabled efficacious in vivo imaging of PBR expressing tissues in an animal model

  17. Effect of introduction atoms on effective exchange field in ferrimagnetic rare earth compounds and 3d-transition metal compounds such as R2Fe17 and RFe11Ti

    International Nuclear Information System (INIS)

    Nikitin, S.A.; Tereshina, I.S

    2003-01-01

    The magnetic properties of the ferrimagnetic compounds R 2 Fe 17 and RFe 11 Ti, as well as their hydrides and nitrides are studied. The change in the exchange fields, effecting the rare earth (RE) ions both from the side of the Fe sublattice and from the side of other RE ions in the process of hydrogenation and nitration is determined and Curie temperature dependence of the source compounds, their hydrides and nitrides on the de Genes factor is identified. It is established that in the course of the light atoms (H and N) introduction into the crystalline lattice of the R 2 Fe 17 and RFe 11 Ti compounds there takes place significant increase in the Curie temperature, in the Fe-Fe exchange interactions and decrease in the R-R interactions. This may be interpreted as the result of the oc curing changes in the electron structures of such compounds and indirect exchange interactions [ru

  18. (E-3-Hydroxy-13-methyl-16-[4-(methylsulfanylbenzylidene]-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H-one

    Directory of Open Access Journals (Sweden)

    R. Murugan

    2009-01-01

    Full Text Available In the title compound, C26H28O2S, the dihedral angles between the mean plane of the five membered ring and the 4-(methylsulfanylbenzylidine ring in the two crystallographically independent molecules are 34.05 (10 and 40.53 (15°. The packing is stabilized by intermolecular O—H...O and C—H...O interactions.

  19. Magnetic properties and tunable magneto-caloric effect in La0.8Ce0.2Fe11.5-xCoxSi1.5C0.2 (x = 0.3, 0.5, and 0.7) compounds

    Science.gov (United States)

    Wu, Qiming; Wang, Xiangjie; Ding, Zan; Li, Lingwei

    2018-05-01

    The magnetic and magneto-caloric properties in the ternary elementals doped La0.8Ce0.2Fe11.5-xCoxSi1.5C0.2 (x = 0.3, 0.5, and 0.7) compounds were studied. With the increases of Co content x, the Curie temperature TC increases and the thermal hysteresis decreases. All the compounds undergo a second-order magnetic phase transition and exhibit a considerable reversible tunable magneto-caloric effect. The values of maximum magnetic entropy change (-ΔSMmax) and the Relative Cooling Power (RCP) are kept at same high level with different Co content. Under a magnetic field change of 0-5 T, the values of -ΔSMmax for La0.8Ce0.2Fe11.5-xCoxSi1.5C0.2 are 10.5, 10.7, and 9.8 J/kg K for x = 0.3, 0.5, and 0.7, respectively. The corresponding values of RCP are 267.1, 289.9, and 290.2 J/kg.

  20. 18F- and 11C-labelling of quantum dots with n.c.a. [18F]fluoroethyltosylate and [11C]methyliodide. A feasibility study

    International Nuclear Information System (INIS)

    Patt, M.; Schildan, A.; Habermann, B.; Mishchenko, O.; Patt, J.T.; Sabri, O.

    2010-01-01

    Quantum dots functionalized on the outer surface with either amino- or carboxyl functions were labelled with [ 18 F]fluoroethyltosylate and [ 11 C]methyliodide in order to use the positron emitter-labelled fluorescence agents for multimodality imaging techniques, i.e. fluorescence imaging and positron emission tomography. 18 F-Labelling of both compounds was realized with yields up to 5% as determined by size exclusion chromatography, which is twice as much as reported in literature before [1]. 11 C-Labelling of amino- and carboxyl-QDs proceeded with good yields (up to 45 and 35%, respectively) under optimized reaction conditions. In general for both QD-types and both labelling agents the labelling yield increased with the amount of QDs used in the reaction as well as with reaction time and reaction temperature. (author)

  1. Test-retest repeatability of myocardial blood flow and infarct size using {sup 11}C-acetate micro-PET imaging in mice

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, Etienne; Renaud, Jennifer M.; McDonald, Matthew; Klein, Ran; DaSilva, Jean N.; Beanlands, Rob S.B.; DeKemp, Robert A. [University of Ottawa Heart Institute, National Cardiac PET Centre, Ottawa, Ontario (Canada)

    2015-09-15

    Global and regional responses of absolute myocardial blood flow index (iMBF) are used as surrogate markers to assess response to therapies in coronary artery disease. In this study, we assessed the test-retest repeatability of iMBF imaging, and the accuracy of infarct sizing in mice using {sup 11}C-acetate PET. {sup 11}C-Acetate cardiac PET images were acquired in healthy controls, endothelial nitric oxide synthase (eNOS) knockout transgenic mice, and mice after myocardial infarction (MI) to estimate global and regional iMBF, and myocardial infarct size compared to {sup 18}F-FDG PET and ex-vivo histology results. Global test-retest iMBF values had good coefficients of repeatability (CR) in healthy mice, eNOS knockout mice and normally perfused regions in MI mice (CR = 1.6, 2.0 and 1.5 mL/min/g, respectively). Infarct size measured on {sup 11}C-acetate iMBF images was also repeatable (CR = 17 %) and showed a good correlation with the infarct sizes found on {sup 18}F-FDG PET and histopathology (r{sup 2} > 0.77; p < 0.05). {sup 11}C-Acetate micro-PET assessment of iMBF and infarct size is repeatable and suitable for serial investigation of coronary artery disease progression and therapy. (orig.)

  2. Synthesis, biodistribution and in vitro evaluation of brain permeable high affinity type 2 cannabinoid receptor agonists [11C]MA2 and [18F]MA3

    Directory of Open Access Journals (Sweden)

    Muneer Ahamed

    2016-09-01

    Full Text Available Abstract The type 2 cannabinoid receptor (CB2 is a member of the endocannabinoid system and is known for its important role in (neuroinflammation. A PET-imaging agent that allows in vivo visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and in vitro evaluation of a carbon-11 ([11C]MA2 and a fluorine-18 ([18F]MA3 labeled analogue of a highly potent N-arylamide oxadiazole CB2 agonist (EC50 = 0.015 nM. MA2 and MA3 behaved as potent CB2 agonist (EC50: 3 nM and 0.1 nM, respectively and their in vitro binding affinity for hCB2 was found to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl group was found to have higher binding affinity and EC50 values when compared to the originally reported trifluoromethyl analogue 12. [11C]MA2 and [18F]MA3 were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [11C]MA2 and [18F]MA3 are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for in vivo imaging of brain CB2 receptors. However in view of its higher affinity and selectivity, further detailed evaluation of MA3 as a PET tracer for CB2 is warranted.

  3. The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11 C]-raclopride and [11 C]-(+)-PHNO PET.

    Science.gov (United States)

    Caravaggio, Fernando; Ku Chung, Jun; Plitman, Eric; Boileau, Isabelle; Gerretsen, Philip; Kim, Julia; Iwata, Yusuke; Patel, Raihaan; Chakravarty, M Mallar; Remington, Gary; Graff-Guerrero, Ariel

    2017-11-01

    Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D 2/3 receptors (D 2/3 R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D 2/3 R availability measured with an antagonist radiotracer ([ 11 C]-raclopride) versus an agonist radiotracer ([ 11 C]-(+)-PHNO) were examined. Data from 62 subjects scanned with [ 11 C]-raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [ 11 C]-(+)-PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1-weighted images using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume. For [ 11 C]-(+)-PHNO, ventral caudate volumes were positively correlated with BP ND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BP ND in the VS. With [ 11 C]-raclopride, BP ND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BP ND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus. Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D 2/3 R and brain morphology are observed. Hum Brain Mapp 38:5519-5534, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. (E-2,2′-[3-(2-Nitrophenylprop-2-ene-1,1-diyl]bis(3-hydroxycyclohex-2-en-1-one

    Directory of Open Access Journals (Sweden)

    Joo Hwan Cha

    2012-01-01

    Full Text Available In the title compound, C21H21NO6, each of the cyclohexenone rings adopts a half-chair conformation. Each of the pairs of hydroxy and carbonyl O atoms are oriented to allow for the formation of intramolecular O—H...O hydrogen bonds, which are typical of xanthene derivatives.

  5. Improved sensitivity of human brain MAO B measurement using deuterium substituted [{sup 11}C]L-deprenyl ([{sup 11}C]L-deprenyl-D2)

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Volkow, N.D.; Wang, G.J. [Brookhaven National Laboratory, Upton, NY (United States)] [and others

    1995-05-01

    Post-mortem reports that human brain monoamine oxidase B (MAO B) increases in normal aging and neurodegenerative disorders due to the proliferation of MAO B-rich glial cells suggest that PET measures of MAO B may track gliosis. We have recently shown that the MAO B tracer [{sup 11}C]L-deprenyl has limited sensitivity in regions of high MAO B due to its rapid rate of trapping. This limits its utility for measuring MAO B in brain regions where MAO B is higher and/or where blood flow is low. We have recently demonstrated that [{sup 11}C]L-deprenyl-D2 has improved sensitivity in regions of high MAO B due to the deuterium isotope effect which reduces the rate of trapping. We report studies [{sup 11}C]L-deprenyl-D2 in normal human brain in 16 healthy men and women (age range 23-73) to assess tracer sensitivity, regional distribution, and reproducibility. Graphical analysis for irreversible systems was used to calculate Ki (influx constant) as an index of MAO B concentration in different brain regions. The uptake of carbon-11 in different brain regions was rapid, peaking at 5 minutes and plateauing from 30-60 minutes after an initial clearance. MAO B was highest in subcortical regions: thalamus{ge}basal ganglia>cingulate gyrus>frontal cortex=occipital cortex=cerebellum in agreement with post-mortem measurements. Ki values were highly correlated within an individual. Repeated measures at 1-4 week intervals were highly correlated (r=0.9; p=0.0001). In women (n=8: age range 23-73), Ki increased with increasing age for 8 brain regions (p < 0.04). Though men (N=8; age range 34-70) showed no correlation with age, a larger sample size is needed to adequately assess trends. In summary, the use of [{sup 11}C]L-deprenyl-D2 improves the measurement of MAO B in the human brain permitting its investigation as a positive tracer for glial cell proliferation in neurodegenerative disorders.

  6. Structural and theoretical study of 1-[1-oxo-3-phenyl-(2-benzosulfonamide)-propyl amido] - anthracene-9,10-dione to be i-motif inhibitor

    Science.gov (United States)

    Vatsal, Manu; Devi, Vandna; Awasthi, Pamita

    2018-04-01

    The 1-[1-oxo-3-phenyl-(2-benzosulfonamide)-propyl amido] - anthracene-9,10-dione (BPAQ) an analogue of anthracenedione class of antibiotic has been synthesized. To characterize molecular functional groups FT-IR and FT-Raman spectrum were recorded and vibrational frequencies were assigned accordingly. The optimized geometrical parameters, vibrational assignments, chemical shifts and thermodynamic properties of title compound were computed by ab initio calculations at Density Functional Theory (DFT) method with 6-31G(d,p) as basis set. The calculated harmonic vibrational frequencies of molecule were then analysed in comparison to experimental FT-IR and Raman spectrum. Gauge independent atomic orbital (GIAO) method was used for determining, (1H) and carbon (13C) nuclear magnetic resonance (NMR) spectra of the molecule. Molecular parameters were calculated along with its periodic boundary conditions calculation (PBC) analysis supported by X-ray diffraction studies. The frontier molecular orbital (HOMO, LUMO) analysis describes charge distribution and stability of the molecule which concluded that nucleophilic substitution is more preferred and the mullikan charge analysis also confirmed the same. Further the title compound showed an inhibitory action at d(TCCCCC), an intermolecular i-motif sequence, hence molecular docking study suggested the inhibitory activity of the compound at these junction.

  7. New metal-organic frameworks of [M(C6H5O7)(C6H6O7)(C6H7O7)(H2O)] . H2O (M=La, Ce) and [Ce2(C2O4)(C6H6O7)2] . 4H2O

    International Nuclear Information System (INIS)

    Weng Shengfeng; Wang, Yun-Hsin; Lee, Chi-Shen

    2012-01-01

    Two novel materials, [M(C 6 H 5 O 7 )(C 6 H 6 O 7 )(C 6 H 7 O 7 )(H 2 O)] . H 2 O (M=La(1a), Ce(1b)) and [Ce 2 (C 2 O 4 )(C 6 H 6 O 7 ) 2 ] . 4H 2 O (2), with a metal-organic framework (MOF) were prepared with hydrothermal reactions and characterized with photoluminescence, magnetic susceptibility, thermogravimetric analysis and X-ray powder diffraction in situ. The crystal structures were determined by single-crystal X-ray diffraction. Compound 1 crystallized in triclinic space group P1-bar (No. 2); compound 2 crystallized in monoclinic space group P2 1 /c (No. 14). The structure of 1 is built from a 1D MOF, composed of deprotonated citric ligands of three kinds. Compound 2 contains a 2D MOF structure consisting of citrate and oxalate ligands; the oxalate ligand arose from the decomposition in situ of citric acid in the presence of Cu II ions. Photoluminescence spectra of compounds 1b and 2 revealed transitions between the 5d 1 excited state and two levels of the 4f 1 ground state ( 2 F 5/2 and 2 F 7/2 ). Compounds 1b and 2 containing Ce III ion exhibit a paramagnetic property with weak antiferromagnetic interactions between the two adjacent magnetic centers. - Graphical Abstract: [M(C 6 H 5 O 7 )(C 6 H 6 O 7 )(C 6 H 7 O 7 )(H 2 O)] . H 2 O (M=La(1a), Ce(1b)) and [Ce 2 (C 2 O 4 )(C 6 H 6 O 7 ) 2 ] . 4H 2 O (2)—with 1D and 2D structures were synthesized and characterized. Highlights: ► Two MOF – [M(C 6 H 5 O 7 )(C 6 H 6 O 7 )(C 6 H 7 O 7 )(H 2 O)] . H 2 O (M=La(1a), Ce(1b)) and [Ce 2 (C 2 O 4 )(C 6 H 6 O 7 ) 2 ] . 4H 2 O (2) – with 1D and 2D structures. ► The adjacent chains of the 1D framework were correlated with each other through an oxalate ligand to form a 2D layer structure. ► The source of the oxalate ligand was the decomposition in situ of citric acid oxidized in the presence of Cu II ions.

  8. Crystallographic characterization of divalent organosamarium compound (C5H5)2Sm(THF)2

    International Nuclear Information System (INIS)

    Jagannatha Swamy, S.

    2002-01-01

    The single pot reaction between SmX 2 (X = Cl - , I - ) and BuLi in THF at -40 degC, followed by the addition of C 5 H 5 - Na + results in a dark red solution. Leaving the concentrated reaction mixture at -25 degC for two days in a deep freezer results in the formation of the crystals of the compound, (C 5 H 5 ) 2 ; Sm(THF) 2 . The compound is insoluble in any solvent and it has been characterized by conventional methods. The crystals are monoclinic with space group C2/c, and a = 13.416(1), b = 9.644(1), c = 14.129(2) pm, β109.873(9) 0 and z = 4 for ρcalcd = 1.64 g cm -3 . Least squares refinement on the basis of 1804 observed reflections has led to a final R value of 0.037 and R w = 0.054. (author)

  9. Studies on 16α-Hydroxylation of Steroid Molecules and Regioselective Binding Mode in Homology-Modeled Cytochrome P450-2C11

    Directory of Open Access Journals (Sweden)

    Hamed I. Ali

    2011-01-01

    Full Text Available We investigated the 16α-hydroxylation of steroid molecules and regioselective binding mode in homology-modeled cytochrome P450-2C11 to correlate the biological study with the computational molecular modeling. It revealed that there was a positive relationship between the observed inhibitory potencies and the binding free energies. Docking of steroid molecules into this homology-modeled CYP2C11 indicated that 16α-hydroxylation is favored with steroidal molecules possessing the following components, (1 a bent A-B ring configuration (5β-reduced, (2 C-3 α-hydroxyl group, (3 C-17β-acetyl group, and (4 methyl group at both the C-18 and C-19. These respective steroid components requirements were defined as the inhibitory contribution factor. Overall studies of the male rat CYP2C11 metabolism revealed that the above-mentioned steroid components requirements were essential to induce an effective inhibition of [3H]progesterone 16α-hydroxylation. As far as docking of homology-modeled CYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also found that the distance between heme iron and C16α-H was between 4 to 6 Å and that the related angle was in the range of 180±45∘.

  10. [11C]UCB-A, a novel PET tracer for synaptic vesicle protein 2 A

    International Nuclear Information System (INIS)

    Estrada, Sergio; Lubberink, Mark; Thibblin, Alf; Sprycha, Margareta; Buchanan, Tim; Mestdagh, Nathalie; Kenda, Benoit; Mercier, Joel; Provins, Laurent; Gillard, Michel; Tytgat, Dominique; Antoni, Gunnar

    2016-01-01

    Introduction: Development of a selective and specific high affinity PET tracer, [ 11 C]UCB-A, for the in vivo study of SV2A expression in humans. Radiochemistry and preclinical studies in rats and pigs including development of a tracer kinetic model to determine V T . A method for the measurement of percent intact tracer in plasma was developed and the radiation dosimetry was determined in rats. Results: 3–5 GBq of [ 11 C]UCB-A could be produced with radiochemical purity exceeding 98% with a specific radioactivity of around 65 GBq/μmol. In vitro binding showed high selective binding towards SV2A. [ 11 C]UCB-A displayed a dose-dependent and reversible binding to SV2A as measured with PET in rats and pigs and the V T could be determined by Logan analysis. The dosimetry was favorable and low enough to allow multiple administrations of [ 11 C]UCB-A to healthy volunteers, and the metabolite analysis showed no sign of labeled metabolites in brain. Conclusions: We have developed the novel PET tracer, [ 11 C]UCB-A, that can be used to measure SV2A expression in vivo. The dosimetry allows up to 5 administrations of 400 MBq of [ 11 C]UCB-A in humans. Apart from measuring drug occupancy, as we have shown, the tracer can potentially be used to compare SV2A expression between individuals because of the rather narrow range of baseline V T values. This will have to be further validated in human studies.

  11. Biodistribution and radiation dosimetry of [11C]DASB in baboons

    International Nuclear Information System (INIS)

    Belanger, Marie-Jose; Simpson, Norman R.; Wang, Theodore

    2004-01-01

    Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [ 11 C]DASB ([ 11 C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [ 11 C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183±5 MBq/2.3±1.0 nmol of [ 11 C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6x10 -2 mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [ 11 C]DASB. In the United States, the absorbed dose to the lungs would limit [ 11 C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female

  12. Radioisotope tracer study of co-reactions of methanol with ethanol using 11C-labelled methanol over alumina and H-ZSM-5

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Kovacs, Z.; Kumar, N.; Salmi, T.; Murzin, D.Yu

    2005-01-01

    Complete text of publication follows. The transformation of methanol has been investigated over alumina and H-ZSM-5 in our previous experiments by 11 C-radioisotope tracing. The main product in methanol conversion over alumina was dimethyl ether due to Lewis acid sites while over H-ZSM-5 mostly hydrocarbons were formed due to both Lewis and Brrnsted acid sites. With increasing temperature first the ethanol was dehydrated to diethyl ether followed by ethene formation over alumina and H-ZSM-5. In this work, 11 C-labelled methanol as radioisotope tracer was added to non-radioactive methanol for investigation of co-reaction with non-radioactive ethanol over alumina and H- ZSM-5. The 11 C-methanol tracer was used to distinguish the methanol derivates and co-reaction derivates of methanol with ethanol against non-radioactive ethanol derivates. The yield of methyl ethyl ether as mixed ether and the influence of ethanol for the yields of C 1 -C 5 hydrocarbons were studied as a function of reaction temperature and contact time. The 11 C-methanol was formed by a radiochemical process from 11 CO 2 produced at cyclotron. The mixture of methanol and ethanol was added to 11 C-methanol and injected to the catalyst. The catalysis was carried out in a glass tube fixed-bed reactor after its pretreatment. The derivates were analyzed by radio-gas chromatography (gas chromatograph with thermal conductivity detector coupled on-line with a radioactivity detector). The comparative analysis of yields of radioactive and non-radioactive products as a function of reaction temperature gives information about the reaction pathways. Over alumina the yields of dimethyl ether and methyl ethyl ether (co-product) as radioactive and diethyl ether with ethene as non-radioactive main products were monitored as a function of reaction temperature and reaction time in the range of 513-593 K. Alongside ethanol derivates the ethene turns into main product in contrast with methyl ethyl ether and diethyl

  13. Carbon-11 labelled ketamine-synthesis, distribution in mice and PET studies in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Shiue, C.-Y.; Vallabhahosula, Shankar; Wolf, Alfred P.; Dewey, Stephen L.; Fowler, Joanna S.; Schlyer, David J.; Arnett, Carroll D.; Zhou Yiguo

    1997-02-01

    No-carrier-added (NCA)[{sup 11}C]({+-})-ketamine (2a) and its enantiomers (+)-2b and (-)-2c were synthesized by methylation of the corresponding norketamine (1a-c) with [{sup 11}C]H{sub 3}I in an overall radiochemical yield of 20% (EOB) with specific activities of 0.35-0.45 Ci/{mu}mole at EOB in a synthesis time of 40 min from EOB. Compound 2a was metabolized rapidly in mouse brain and labeled metabolites appeared in baboon plasma. PET studies of compounds 2a-c in a baboon showed that influx of compounds 2a-c into the brain was high for the first few min but radioactivity then declined rapidly. Although the retention of radioactivity in the baboon striatum was not significantly different for 2a-c 20 min post-injection, graphical analysis of time-activity data for each enantiomer and for the racemate in baboon striatum suggested that (+)-ketamine may interact with receptors slightly more effectively than its (-)-enantiomer or racemate. However, due to its rapid metabolism in the brain and a similar uptake in the striatum and cerebellum, [{sup 11}C]ketamine may not be an ideal tracer for studying NMDA receptor with PET.

  14. Two anti-angiogenic TKI-PET tracers, [11C]axitinib and [11C]nintedanib: Radiosynthesis, in vivo metabolism and initial biodistribution studies in rodents

    International Nuclear Information System (INIS)

    Slobbe, Paul; Poot, Alex J.; Haumann, Rianne; Schuit, Robert C.; Windhorst, Albert D.; Dongen, Guus A.M.S. van

    2016-01-01

    Introduction: Tyrosine kinase inhibitors (TKIs) are very attractive targeted drugs, although a large portion of patients remains unresponsive. PET imaging with EGFR targeting TKIs ([ 11 C]erlotinib and [ 18 F]afatinib) showed promise in identifying treatment sensitive tumors. The aim of this study was to synthesize two anti-angiogenic TKI tracers, [ 11 C]axitinib and [ 11 C]nintedanib, and to evaluate their potential for PET. Methods: Following successful tracer synthesis, biodistribution studies in VU-SCC-OE and FaDu xenograft bearing mice were performed. Furthermore, tracer stability studies in mice were performed employing (radio-)HPLC and LC–MS/MS techniques. For [ 11 C]nintedanib an LC–MS/MS method was developed to detect the primary carboxylic acid metabolite, resulting from methylester cleavage, in plasma and tumors, because this metabolite is postulated to be important for nintedanib efficacy. LC–MS/MS was also explored to assess the metabolic fate of [ 11 C]axitinib in vivo, since axitinib has an isomerizable double bond. Results: [ 11 C]axitinib and [ 11 C]nintedanib were successfully synthesized with 10.5 ± 2.6% and 25.6 ± 3.3% radiochemical yield (corrected for decay), respectively. Biodistribution studies only demonstrated tumor uptake of [ 11 C]nintedanib in FaDu xenografts of 1.66 ± 0.02% ID/g at 60 min p.i. In vivo stability analysis of [ 11 C]axitinib at 45 min p.i. revealed the formation of predominantly non-polar metabolites (36.6 ± 6.8% vs 47.1 ± 8.4% of parent tracer and 16.3 ± 2.1% of polar metabolites), while for [ 11 C]nintedanib mostly polar metabolites were found (70.9 ± 4.1 vs 26.7 ± 3.9% of parent tracer and only 2.4 ± 1.6 of a non-polar metabolites). No isomerization of [ 11 C]axtinib was observed in vivo; however, a sulfoxide metabolite could be detected using LC–MS/MS. For [ 11 C]nintedanib, LC–MS/MS revealed formation of the reported primary carboxylic acid metabolite when in vitro plasma incubations were performed

  15. Structure determination of two structural analogs, named 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) by synchrotron X-ray powder diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Gündoğdu, Gülsüm; Aytaç, Sevim Peri; Müller, Melanie; Tozkoparan, Birsen; Kaynak, Filiz Betül

    2017-12-01

    Two novel compounds, 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) (1) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) (2), have been designed and synthesized as cytotoxic agents. The compounds were characterized by infrared, proton nuclear magnetic resonance, mass spectral data, elemental analysis and X-ray powder diffraction. The present study comprises spectral data and crystal structures of these novel compounds determined from synchrotron X-ray powder diffraction data. The structure solutions were obtained by simulated annealing. The final structures were achieved by Rietveld refinement using soft restraints for all bond lengths, bond angles, and planar groups. Both compounds crystallize in space group$P\\bar 1$,Z= 2, with the unit-cell parametersa= 6.37433(9),b= 11.3641(2),c= 14.09115(19) Å,α= 80.1740(8)°,β= 85.1164(8)°,γ= 80.9831(10)°,V= 991.55(3) Å3of compound (1) anda= 6.53736(6),b= 11.55725(15),c= 14.01373(13) Å,α= 80.3323(7)°,β= 84.8939(6)°,γ= 79.3954(8)°,V= 1024.08(2) Å3of compound (2). Structural analyses reveal that the title compounds are isostructural.

  16. Magnetocaloric effect in the La0.8Ce0.2Fe11.4-xCoxSi1.6 compounds

    International Nuclear Information System (INIS)

    Wang, G.F.; Song, L.; Li, F.A.; Ou, Z.Q.; Tegus, O.; Brueck, E.; Buschow, K.H.J.

    2009-01-01

    The effects of substitution of Co for Fe on the magnetic and magnetocaloric properties of La 0.8 Ce 0.2 Fe 11.4-x Co x Si 1.6 (0, 0.2, 0.4, 0.6, 0.8 and 1.0) compounds have been investigated. X-ray diffraction shows that all compounds crystallize in the NaZn 13 -type structure. Magnetic measurements show that the Curie temperature (T C ) can be tuned between 184 and 294 K by changing the Co content from 0 to 1. A field-induced methamagnetic transition occurs in samples with x=0, 0.2 and 0.4. The magnetic entropy changes of the compounds have been determined from the isothermal magnetization measurements by using the Maxwell relation.

  17. (4-Chloroacetanilido-κ2N,Obis[2-(pyridin-2-ylphenyl-κ2C1,N]iridium(III

    Directory of Open Access Journals (Sweden)

    Lijun Sun

    2013-02-01

    Full Text Available In the neutral mononuclear iridium(III title compound, [Ir(C8H7ClNO(C11H8N2], the IrIII atom adopts an octahedral geometry, and is coordinated by two 2-phenylpyridyl ligands and one anionic 4-chloroacetanilide ligand. The 2-phenylpyridyl ligands are arranged in a cis-C,C′ and cis-N,N′ fashion. Each 2-phenylpyridyl ligand forms a five-membered ring with the IrIII atom. The 2-phenylpyridyl planes are perpendicular to each other [dihedral angle = 89.9 (1°]. The Ir—C and Ir—N bond lengths are comparable to those reported for related iridium(III 2-phenylpyridyl complexes. The remaining two coordination sites are occupied by the amidate N and O atoms, which form a four-membered ring with the iridium atom (Ir—N—C—O. The amidate plane is nearly perpendicular to both 2-phenylpyridyl ligands [dihedral angles = 87.8 (2 and 88.3 (2°].

  18. Crystal structure of chlorido(dimethyl sulfoxide-κSbis[4-(pyridin-2-ylbenzaldehyde-κ3C2,N]iridium(III acetonitrile monosolvate

    Directory of Open Access Journals (Sweden)

    Andrew J. Peloquin

    2017-09-01

    Full Text Available The title compound, [IrCl(C12H8NO2{(CH32SO}]·H3CCN or [IrCl(fppy2(DMSO]·H3CCN [where fppy is 4-(pyridin-2-ylbenzaldehyde and DMSO is dimethyl sulfoxide], is a mononuclear iridium(III complex including two fppy ligands, a sulfur-coordinating DMSO ligand, and one terminal chloride ligand that define a distorted octahedral coordination sphere. The complex crystallizes from 1:1 DMSO–acetonitrile as an acetonitrile solvate. In the crystal, weak C—H...O and C—H...N hydrogen-bonding interactions between adjacent complexes and between the acetonitrile solvent and the complex consolidate the packing.

  19. Automated preparation of the dopamine D{sub 2/3} receptor agonist ligand [{sup 11}C]-(+)-PHNO for human PET imaging studies

    Energy Technology Data Exchange (ETDEWEB)

    Plisson, Christophe, E-mail: Christophe.2.plisson@gsk.com [GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London W12 0NN (United Kingdom); Huiban, Mickael; Pampols-Maso, Sabina; Singleton, Goerkem; Hill, Samuel P.; Passchier, Jan [GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London W12 0NN (United Kingdom)

    2012-02-15

    Carbon-11 labelled (+)-4-Propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([{sup 11}C]-(+)-PHNO) is used as a high-affinity state, dopamine D{sub 2/3} receptor ligand in clinical PET studies. To facilitate its use, robust, rapid, efficient and GMP compliant methods are required for the manufacturing and QC testing processes. Additionally, to allow for full quantification of the resulting signal in the CNS, a reliable method is required to establish the parent plasma concentration over the course of the scan. This paper provides high-quality methods to support clinical application of [{sup 11}C]-(+)-PHNO. - Highlights: Black-Right-Pointing-Pointer Fully automated synthesis of [{sup 11}C]-(+)-PHNO. Black-Right-Pointing-Pointer Rapid multi-step synthesis and QC analysis. Black-Right-Pointing-Pointer Reproducible synthesis process typically yielding more than 3 GBq of [{sup 11}C]-(+)-PHNO. Black-Right-Pointing-Pointer Very low failure rate.

  20. Interplay between H6PDH and 11β-HSD1 implicated in the pathogenesis of type 2 diabetes mellitus.

    Science.gov (United States)

    Yao, Fan; Chen, Li; Fan, Zheng; Teng, Fei; Zhao, Yali; Guan, Fengying; Zhang, Ming; Liu, Yanjun

    2017-09-01

    Extensive studies have been performed on the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in metabolic diseases. Our previous study reported glucose could directly regulate hexose-6-phosphate dehydrogenase (H6PDH) and 11β-HSD1. Recently, we further investigated the interplay of H6PDH and 11β-HSD1 and their roles in hepatic gluconeogenesis and insulin resistance to elucidate the importance of H6PDH and 11β-HSD1 in pathogenesis of type 2 diabetes mellitus (T2DM). T2DM rats model and H6PDH or 11β-HSD1 siRNA transfected in CBRH-7919 cells were used to explore the effect of H6PDH and 11β-HSD1 in T2DM. The results showed that the expression and activity of H6PDH and 11β-HSD1 in livers of diabetic rats were increased, with the expressions of PEPCK and G6Pase or liver corticosterone increased apparently. It also showed that H6PDH siRNA and 11β-HSD1 siRNA could inhibit the protein expression and enzyme activity by each other. With H6PDH siRNA, the enhancement of gluconeogenesis was blocked and insulin resistance stimulated by corticosterone was reduced. H6PDH and 11β-HSD1 might be the effective and prospective targets for T2DM and metabolic syndromes, based on the interplay between these two enzymes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Synthesis of 4-(3-t-butylamino-2-hydroxypropoxy)- benzimidazol -2 (/sup 11/C)-one (CGP 12177)

    Energy Technology Data Exchange (ETDEWEB)

    Boullais, C; Crouzel, C; Syrota, A

    1986-05-01

    4-(3-t-butylamino-2-hydroxypropoxy)-benzimidazol-2 (/sup 11/C)-one (CGP 12177) was synthesized in a short time (30 min) and with a specific activity of 130 mCi/..mu..Mo1 for ..beta.. receptor studies by the positron emission tomography. The radioactive reagent was /sup 11/C-phosgene and the starting material 1-(3-t-butylamino-2-hydroxypropoxy)-2,3-diamino benzene.

  2. 2-Fluoro-5-(4-fluorophenylpyridine

    Directory of Open Access Journals (Sweden)

    Fazal Elahi

    2012-07-01

    Full Text Available In the title compound, C11H7F2N, the fluorobenzene and the 2-fluoropyridine rings are oriented at a dihedral angle of 37.93 (5°. In the crystal, only van der Waals interactions occur.

  3. 2-[2-Chloro-5-(trifluoromethylphenyl]hexahydropyrimidine monohydrate

    Directory of Open Access Journals (Sweden)

    Reza Kia

    2008-09-01

    Full Text Available The molecule of the title compound, C11H12ClF3N2·H2O, is a substituted hexahydropyrimidine. There are two crystallographically independent molecules (A and B and two water molecules in the asymmetric unit of the title compound. Intermolecular C—H...Cl (× 2, C—H...F, and C—H...N (× 2 hydrogen bonds generate S(5 ring motifs. The dihedral angle between the two benzene rings is 8.17 (11°. The F atoms in molecule B are disordered over four positions with refined site-occupancies of ca 0.35/0.19/0.29/0.17 for the four components. In the crystal structure, molecules are arranged into one-dimensional extended chains along the c axis and are further stacked along the a axis by directed four-membered O—H...O—H interactions, forming two-dimensional networks parallel to the ac plane. The short distances between the centroids of the benzene rings (3.8002–3.8327 Å indicate the existence of π–π interactions. In addition, the crystal structure is further stabilized by N—H...O, O—H...N (× 4, N—H...Cl and C—H...O (× 2 hydrogen-bonding interactions.

  4. Reaction of (CP(2)asterisk-lnH)(2) (ln=Y, La) and CP(2)asterisk-Y(2-C(6)H(4)CH(2)NMe(2)) with esters and amides and molecular-structure of [CP(2)asterisk-Y(mu- ocme=chc(oet)o)](2)

    NARCIS (Netherlands)

    Deelman, B.J; Wierda, F.; Meetsma, A.; Teuben, J.H

    1995-01-01

    The activation of esters and amides by (Cp(2)*LnH)(2) [Ln = Y (1a), Ln = La (1b), Cp*=C(5)Me] and Cp(2)*Y(2-C(6)H(4)CH(2)NMe(2)) (2) is described. Compounds 1a and 1b react with ethyl acetate to form Cp(2)*YOEt (3a) and Cp(2)*LaOEt (30). With 1a and ethyl benzoate a 1:1 mixture of 3a and

  5. N-{4-[4-(4-Fluorophenyl-1-(2-methoxyethyl-2-methylsulfanyl-1H-imidazol-5-yl]-2-pyridyl}-2-methyl-3-phenylpropionamide

    Directory of Open Access Journals (Sweden)

    Stefan Laufer

    2009-12-01

    Full Text Available In the crystal structure of the title compound, C28H29FN4O2S, the imidazole ring makes dihedral angles of 11.85 (7, 73.33 (7 and 22.83 (8° with the 4-fluorophenyl, pyridine and phenyl rings, respectively. The 4-fluorophenyl ring makes dihedral angles of 77.91 (7 and 26.93 (8° with the pyridine and phenyl rings, respectively. The phenyl and pyridine rings are nearly perpendicular, making a dihedral angle of 86.47 (9°. The crystal packing shows an intermolecular N—H...O hydrogen-bonding interaction between the N—H and carbonyl groups of the amide functions.

  6. Synthesis and in-vivo evaluation of C-11 p-PVP-MEMA as a PET radioligand for imaging nicotinic receptors

    International Nuclear Information System (INIS)

    Paine, T.; Kassiou, M.; Dolle, F.; Langle, S.; Roger, G.; Lagnel-de Bruin, B.; Hinnen, F.; Valette, H.; Bottlaender, M.; Fulton, R.R.; Henderson, D.J.; Coster, M.J.; Kassiou, M.

    2008-01-01

    Within the class of (4-pyridinyl)vinyl-pyridines developed by Abbott laboratories as potent neuronal nicotinic acetylcholine receptor ligands, p-PVP-MEMA ({oro-5-((E)-2-pyridin-4-yl-vinyl) pyridin-3-yloxy]-1-methylethyl} is the lead compound of a novel series that do not display the traditional nicotinic-like pyrrole-ring but still possessing high sub-nanomolar affinity (K-i 0.077 nm-displacement of [H-3](-)cytisine from whole rat brain synaptic membranes). In the present study, p-PVP-MEMA and its nor-derivative ({oro-5-((E)-2-pyridin-4- yl-vinyl) pyridin-3-yloxy]-1-methylethyl} as precursor for labelling with the short-lived positron-emitter carbon-11 (T 1/2 = 20.4 min) were synthesized in 10 chemical steps from 2-hydroxy-5-nitropyridine and Boc-D-alanine. N-Alkylation of nor-p-PVP-MEMA with [C-11] methyl iodide afforded [C-11]p-PVP-MEMA (≥ 98% radiochemically pure, specific activity of 86.4 GBq μ mol -1 ) in 2% (non-decay corrected and non-optimized) radiochemical yield, in 34 min (including HPLC purification and formulation). Preliminary positron emission tomography PET) results obtained in a Papio hamadryas baboon showed that [C-11] p-PVP-MEMA is not a suitable PET-radioligand. (authors)

  7. 3,5-Bis[1-acetyl-5-(4-chlorophenyl-4,5-dihydro-1H-pyrazol-3-yl]-2,6-dimethylpyridine tetrahydrofuran solvate

    Directory of Open Access Journals (Sweden)

    Qun Qian

    2008-07-01

    Full Text Available In the title compound, C29H27Cl2N5O2·C4H8O, the polycyclic system is composed of three parts: one central pyridine ring substituted by two functionalized pyrazoline rings. The dihedral angles between the central pyridine plane and pyrazoline planes are 5.11 (1 and 13.99 (1°, whereas the dihedral angles between each chlorophenyl plane and the attached pyrazoline planes are 88.65 (1 and 83.87 (1°. Molecules are linked by intermolecular C—H...O hydrogen bonds, forming a three-dimensional network.

  8. Structure of Chloro bis(1,10-phenanthroline)Cobalt(II) Complex, [Co(phen)2(Cl)(H2O)]Cl · 2H2O

    International Nuclear Information System (INIS)

    Zhao, Pu Su; Lu, Lu De; Jian, Fang Fang

    2003-01-01

    The crystal structure of [Co(phen) 2 (Cl)(H 2 O)] Cl · 2H 2 O(phen=1,10-phenanthroline) has been determined by X-ray crystallography. It crystallizes in the triclinic system, space group P 1 , with lattice parameters a=9.662(2), b=11.445(1), c=13.037(2)A, α=64.02(1), β=86.364(9), γ=78.58(2) .deg., and Z=2. The coordinated cations contain a six-coordinated cobalt atom chelated by two phen ligands and one chloride anion and one water ligand in cis arrangement. In addition to the chloride coordinated to the cobalt, there are one chloride ion and four water molecules which complete the crystal structure. In the solid state, the title compound forms three dimensional network structure through hydrogen bonds, within which exists the strongest hydrogen bond (O(3)-O(4)=2.33A). The intermolecular hydrogen bonds connect the [Co(phen) 2 (Cl)(H 2 O)] 1+ , H 2 O moieties and chloride ion

  9. Dehalogenation of vicinal dihalo compounds by 1,1'-bis(trimethylsilyl)-1H,1'H-4,4'-bipyridinylidene for giving alkenes and alkynes in a salt-free manner.

    Science.gov (United States)

    Rej, Supriya; Pramanik, Suman; Tsurugi, Hayato; Mashima, Kazushi

    2017-12-07

    We report a transition metal-free dehalogenation of vicinal dihalo compounds by 1,1'-bis(trimethylsilyl)-1H,1'H-4,4'-bipyridinylidene (1) under mild conditions, in which trimethylsilyl halide and 4,4'-bipyridine were generated as byproducts. The synthetic protocol for this dehalogenation reaction was effective for a wide scope of dibromo compounds as substrates while keeping the various functional groups intact. Furthermore, the reduction of vicinal dichloro alkanes and vicinal dibromo alkenes also proceeded in a salt-free manner to afford the corresponding alkenes and alkynes.

  10. Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-11C-propyl]n-propylnorapomorphine

    DEFF Research Database (Denmark)

    Palner, Mikael; McCormick, Patrick; Gillings, Nicolas

    2010-01-01

    Several dopamine D(2) agonist radioligands have been used with positron emission tomography (PET), including [(11)C-]-(-)-MNPA, [(11)C-]-(-)-NPA and [(11)C]-(+)-PHNO. These radioligands are considered particularly powerful for detection of endogenous dopamine release, but they either provide PET ...

  11. Synthesis and characteristics in tumor-bearing mice of N-[11C]methyl-1-deoxynojirimycin and N-[11C]methyl-1-deoxymannojirimycin

    International Nuclear Information System (INIS)

    Ishiwata, Kiichi; Sasaki, Toru; Ishii, Shin-ichi; Senda, Michio; Seki, Hiroyuki; Kitasato Univ.; Nozaki, Tadashi

    1993-01-01

    N-[ 11 C]Methyl-1-deoxynojirimycin ([ 11 C]MDNM) and N-[ 11 C]methyl-1-deoxymannojirimycin ([ 11 C]MDMM) were prepared by 11 C-methylation of 1-deoxynojirimycin (DNM) and 1-deoxymannojirimycin (DMM), which are specific inhibitors of glucosidase and mannosidase, respectively. In mice bearing Ehrich ascitic tumor, the highest uptake of the [ 11 C]MDNM was observed in the kidney, followed by the liver and small intestine, while the tumour uptake was moderate. By MDNM loading, saturable uptake was observed in these tissues. In homogenates of the kidney and tumor tissues, a considerable amount of radioactivity was detected in a high-molecular weight fraction. These results demonstrate that the [ 11 C]MDNM has a potential for imaging the glucosidase activity by positron emission tomography. On the other hand, [ 11 C]MDMM showed lower uptake than [ 11 C]MDNM in the kidney, liver and small intestine and no effect of carrier DMM, suggesting that the [ 11 C]MDMM would not reflect mannosidase activity. (Author)

  12. Tetrakis(μ-benzoato-κ2O:O′bis[(piperidine-κNrhodium

    Directory of Open Access Journals (Sweden)

    Detlef Selent

    2017-02-01

    Full Text Available The title compound, [Rh2(C7H5O24(C5H11N2], an adduct of dimeric rhodium(II benzoate with piperidine, was prepared. The complex lies across an inversion centre with the unique RhII ion in a slightly distorted octahedral coordination environment.

  13. Amyloid imaging in cognitively normal older adults: comparison between {sup 18}F-flutemetamol and {sup 11}C-Pittsburgh compound B

    Energy Technology Data Exchange (ETDEWEB)

    Adamczuk, Katarzyna; Schaeverbeke, Jolien; Neyens, Veerle; Dupont, Patrick [KU Leuven, Laboratory for Cognitive Neurology, Leuven (Belgium); Leuven Institute of Neuroscience and Disease, Alzheimer Research Centre KU Leuven, Leuven (Belgium); Nelissen, Natalie [KU Leuven, Laboratory for Cognitive Neurology, Leuven (Belgium); Oxford University, Department of Psychiatry, Oxford (United Kingdom); Vandenbulcke, Mathieu [University Hospitals Leuven, Old Age Psychiatry Department, Leuven (Belgium); Goffin, Karolien [KU Leuven and University Hospitals Leuven, Nuclear Medicine and Molecular Imaging Department, Leuven (Belgium); Lilja, Johan [GE Healthcare, Uppsala (Sweden); Department of Surgical Sciences, Radiology, Uppsala University Hospital, Uppsala University, Uppsala (Sweden); Hilven, Kelly [KU Leuven, Laboratory for Neuroimmunology, Leuven (Belgium); Laere, Koen van [Leuven Institute of Neuroscience and Disease, Alzheimer Research Centre KU Leuven, Leuven (Belgium); KU Leuven and University Hospitals Leuven, Nuclear Medicine and Molecular Imaging Department, Leuven (Belgium); Vandenberghe, Rik [KU Leuven, Laboratory for Cognitive Neurology, Leuven (Belgium); Leuven Institute of Neuroscience and Disease, Alzheimer Research Centre KU Leuven, Leuven (Belgium); University Hospitals Leuven, Neurology Department, Leuven (Belgium)

    2016-01-15

    Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: {sup 18}F-flutemetamol and {sup 11}C-Pittsburgh compound B (PIB). In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on {sup 18}F-flutemetamol versus {sup 11}C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVR{sub comp}) and, alternatively, according to visual reads. We also determined the correlation between {sup 18}F-flutemetamol and {sup 11}C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. Binary classification based on semiquantitative assessment was concordant between {sup 18}F-flutemetamol and {sup 11}C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between {sup 18}F-flutemetamol and {sup 11}C-PIB SUVR{sub comp} with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. For the definition of preclinical AD based on {sup 18}F-flutemetamol, concordance with {sup 11}C-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region. (orig.)

  14. tert-Butyl 3-(8-bromo-4H,10H-1,2-oxazolo[4,3-c][1]benzoxepin-10-yl-2-methyl-1H-indole-1-carboxylate

    Directory of Open Access Journals (Sweden)

    Ankur Trigunait

    2010-08-01

    Full Text Available In the title compound, C25H23BrN2O4, the seven-membered ring adopts a twisted-boat conformation. The indole ring system is planar within 0.021 (2 Å and the ester group [–C(=O—O—C–] is almost coplanar with it [dihedral angle = 3.0 (2°]. The conformation of the ester group is influenced by intramolecular C—H...O interactions. In the crystal structure, molecules are linked into chains along the b axis by C—H...N hydrogen bonds.

  15. 5-Bromo-4-(3,4-dimethoxyphenylthiazol-2-amine

    Directory of Open Access Journals (Sweden)

    Hazem A. Ghabbour

    2012-06-01

    Full Text Available In the title compound, C11H11BrN2O2S, the thiazole ring makes a dihedral angle of 53.16 (11° with the adjacent benzene ring. The two methoxy groups are slightly twisted from the attached benzene ring with C—O—C—C torsion angles of −9.2 (3 and −5.5 (3°. In the crystal, molecules are linked by a pair of N—H...N hydrogen bonds into an inversion dimer with an R22(8 ring motif. The dimers are further connected by N—H...O hydrogen bonds into a tape along [-110].

  16. Synthesis and preclinical evaluation of carbon-11 labelled N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine as a PET tracer for NR2B subunit-containing NMDA receptors

    International Nuclear Information System (INIS)

    Christiaans, Johannes A.M.; Klein, Pieter J.; Metaxas, Athanasios; Kooijman, Esther J.M.; Schuit, Robert C.; Leysen, Josée E.; Lammertsma, Adriaan A.; Berckel, Bart N.M. van; Windhorst, Albert D.

    2014-01-01

    Introduction: The N-methyl-D-Aspartate (NMDA) receptor plays an important role in learning and memory. Overactivation is thought to play an important role in neurodegenerative disorders such as Alzheimer's disease. Currently, it is not possible to assess N-methyl-D-aspartate receptor (NMDAr) bio-availability in vivo. The purpose of this study was to develop a positron emission tomography (PET) ligand for the NR2B binding site of the NMDA receptor. Methods: N-((5-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was radiolabelled with carbon-11 in the phenyl moiety. Biodistribution and blocking studies were carried out in anaesthetized mice and in non-anaesthetized rats. Results: N-((5-(4-fluoro-2-[ 11 C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was prepared in 49 ± 3% (decay-corrected) yield, affording 4.1 ± 0.3 GBq of formulated product at the end of synthesis with a radiochemical purity of > 99% and with a specific activity of 78 ± 10 GBq/μmol. Conclusion: A new NR2B PET ligand was developed in high yield. [ 11 C]4 readily enters the brain and binds to the NR2B subunit-containing NMDAr in the rodent brain. High sigma-1 receptor binding may, however, limit its future application as a PET probe for imaging the NR2B subunit-containing NMDAr. Anaesthesia has an effect on NMDAr function and therefore can complicate interpretation of preclinical in vivo results. In addition, effects of endogenous compounds cannot be excluded. Despite these potential limitations, further studies are warranted to investigate the values of [ 11 C]4 as an NR2B PET ligand

  17. Synthesis and positron emission tomographic (PET) baboon studies of [{sup 11}C]methadone and R-(-)-[{sup 11}C]methandone

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.; Fowler, J.S.; Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1996-05-01

    Methadone (MET) maintenance has been used successfully for many years in the rehabilitation of heroin addicts. MET, a typical m{mu}-opioid receptor agonist, exists as two enantiomers and is used clinically as the racemic mixture. However, R-(-)-MET has a 10-fold higher affinity for m{mu} receptors than S-(+)-MET (IC{sub 50}: 3.0 nM and 26.4 nM, respectively) and R-(-)-MET is almost entirely responsible for the therapeutic actions of the racemate. In order to examine the pharmacokinetics and stereoselectivity of the drug, we have synthesized both [{sup 11}C]MET and R-(-)-[{sup 11}C]MET. Preparing the precursor by one-step approach to the N-demethylated methadone was precluded as other investigators cited problems with intramolecular cyclization. Therefore, a four-step synthesis using MET (or R-(-)-MET) as starting material was required to obtain the precursor, followed by a two-step radiolabeling synthesis (N-methylation followed by oxidation) to obtain [{sup 11}C]MET (or R-(-)-[{sup 11}C]MET). Comparative PET studies in the same baboon showed peak striatal uptake was 0.022%/cc at 5 minutes with a half time of clearance from peak of 100 minutes for R-(-)-[{sup 11}C]MET and a peak uptake of 0.013%/cc with a half time of 90 min for [{sup 11}C]MET. R-(-)-[{sup 11}C]MET also showed a slower disappearance in plasma. Both tracers showed higher C-11 in basal ganglia (BG), thalamus and midbrain relative to the cerebellum (CB) and occipital cortex (OC) but the BG/OC ratio was higher for R-(-)-[{sup 11}C]MET (1.3 vs 1.1). Pretreatment with naloxone (1 mg/kg, iv) increased R-(-)-[{sup 11}C]MET uptake in all brain regions whereas unlabeled MET slightly increased C-11 clearance in BG, OC and CB. These initial results show higher brain concentration and specificity of the pharmacologically active enantiomer of methadone along with significant non-specific binding.

  18. 2,3-Dibromo-1-(4-chlorophenyl-3-(5-nitro-2-furylpropan-1-one

    Directory of Open Access Journals (Sweden)

    Balakrishna Kalluraya

    2010-12-01

    Full Text Available In the title compound, C13H8Br2ClNO4, the linking –CHBr–CHBr– fragment is disordered over two orientations with refined site occupancies of 0.512 (11 and 0.488 (11. The dihedral angle between the furan ring and the phenyl ring is 21.86 (16°. In the crystal, the molecules are linked into [011] chains by intermolecular C—H...O hydrogen bonds.

  19. Identification, synthesis, and biological evaluation of the metabolites of 3-amino-6-(3'-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6-36), a promising rexinoid lead compound for the development of cancer chemotherapeutic and chemopreventive agents.

    Science.gov (United States)

    Chen, Lian; Conda-Sheridan, Martin; Reddy, P V Narasimha; Morrell, Andrew; Park, Eun-Jung; Kondratyuk, Tamara P; Pezzuto, John M; van Breemen, Richard B; Cushman, Mark

    2012-06-28

    Activation of the retinoid X receptor (RXR), which is involved in cell proliferation, differentiation, and apoptosis, is a strategy for cancer chemotherapy and chemoprevention, and 3-amino-6-(3'-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6-36) (3) is among the few RXR ligands known. The presently reported studies of 3 include its binding to human plasma proteins, metabolic stability using human liver microsomes, metabolism by human liver microsomes and hepatocytes, and in vivo disposition in rat serum, liver, and mammary tissue. Compound 3 was 75% bound to human plasma proteins, and its metabolic stability was much greater than propranolol. One phase I metabolite was formed by human liver microsomes, seven phase I and II metabolites were formed by human hepatocytes, and five metabolites were detected in rat serum and liver after oral administration. The putative metabolites predicted using LC-MS-MS were synthesized to confirm their structures and to provide sufficient material for investigation of induction of RXRE transcriptional activity and inhibition of NFκB.

  20. Hydrothermal synthesis, structural elucidation, spectroscopic studies, thermal behavior and luminescence properties of a new 3-d compound: FeAlF2(C10H8N2)(HPO4)2(H2O)

    Science.gov (United States)

    Bouzidia, Nabaa; Salah, Najet; Hamdi, Besma; Ben Salah, Abdelhamid

    2017-04-01

    The study of metal phosphate has been a proactive field of research thanks to its applied and scientific importance, especially in terms of the development of optical devices such as solid state lasers as well as optical fibers. The present paper seeks to investigate the synthesis, crystal structure, elemental analysis and properties of FeAlF2(C10H8N2)(HPO4)2(H2O) compound investigated by spectroscopic studies (FT-IR and FT-Raman), thermal behavior and luminescence. The Hirshfeld surface analysis and 2-D fingerprint plot have been performed to explore the behavior of these weak interactions and crystal cohesion. This investigation shows that the molecules are connected by hydrogen bonds of the type Osbnd H⋯O and Osbnd H⋯F. In addition, the 2,2'‒bipyridine ligand plays a significant role in the construction of 3-D supramolecular framework via π‒π stacking. FT‒IR and FT‒Raman spectra were used so as to ease the responsibilities of the vibration modes of the title compound. The thermal analysis (TGA) study shows a mass loss evolution as a temperature function. Finally, the optical properties were evaluated by photoluminescence spectroscopy.

  1. Ba{sub 1.63}La{sub 7.39}Si{sub 11}N{sub 23}Cl{sub 0.42}:Ce{sup 3+} - a nitridosilicate chloride with a zeolite-like structure

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter; Oeckler, Oliver [Institute of Mineralogy, Crystallography and Materials Science, Faculty of Chemistry and Mineralogy, Leipzig University, Scharnhorststrasse 20, 04275 Leipzig (Germany); Durach, Dajana; Schnick, Wolfgang [Department of Chemistry, University of Munich (LMU), Butenandtstrasse 5-13, 81377 Munich (Germany)

    2016-05-15

    The nitridosilicate chloride Ba{sub 1.63}La{sub 7.39}Si{sub 11}N{sub 23}Cl{sub 0.42}:Ce{sup 3+} was synthesized by metathesis reaction starting from LaCl{sub 3}, BaH{sub 2}, CeF{sub 3} and the product of the ammonolysis of Si{sub 2}Cl{sub 6}. The title compound is stable towards air and moisture. Diffraction data of a microcrystal were recorded using microfocused synchrotron radiation. X-ray spectroscopy confirms the chemical composition of the crystal. IR spectra corroborate absence of N-H bonds. The compound is homeotypic to Ba{sub 2}Nd{sub 7}Si{sub 11}N{sub 23} and crystallizes in space group Cmmm with a = 11.009(3), b = 23.243(8), c = 9.706(4) Aa and Z = 4, R{sub 1}(all) = 0.0174. According to bond valence sum calculations, some crystallographic positions show complete occupancy by Ba or La whereas others contain significant amounts of both elements. In contrast to the structure prototype Ba{sub 2}Nd{sub 7}Si{sub 11}N{sub 23}, Ba{sub 1.63}La{sub 7.39}Si{sub 11}N{sub 23}Cl{sub 0.42}:Ce{sup 3+} contains chloride ions in channels of the SiN{sub 4} tetrahedra network, hinting at various substitution possibilities of the complex zeolite-like structure. (Copyright copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Pharmacophore modeling and in silico / in vitro screening for human cytochrome P450 11B1 & cytochrome P450 11B2 inhibitors

    Science.gov (United States)

    Akram, Muhammad; Waratchareeyakul, Watcharee; Haupenthal, Joerg; Hartmann, Rolf W.; Schuster, Daniela

    2017-12-01

    Cortisol synthase (CYP11B1) is the main enzyme for the endogenous synthesis of cortisol and its inhibition is a potential way for the treatment of diseases associated with increased cortisol levels, such as Cushing’s syndrome, metabolic diseases, and delayed wound healing. Aldosterone synthase (CYP11B2) is the key enzyme for aldosterone biosynthesis and its inhibition is a promising approach for the treatment of congestive heart failure, cardiac fibrosis, and certain forms of hypertension. Both CYP11B1 and CYP11B2 are structurally very similar and expressed in the adrenal cortex. To facilitate the identification of novel inhibitors of these enzymes, ligand-based pharmacophore models of CYP11B1 and CYP11B2 inhibition were developed. A virtual screening of the SPECS database was performed with our pharmacophore queries. Biological evaluation of the selected hits lead to the discovery of three potent novel inhibitors of both CYP11B1 and CYP11B2 in the submicromolar range (compounds 8-10), one selective CYP11B1 inhibitor (Compound 11, IC50 = 2.5 µM), and one selective CYP11B2 inhibitor (compound 12, IC50 = 1.1 µM), respectively. The overall success rate of this prospective virtual screening experiment is 20.8% indicating good predictive power of the pharmacophore models.

  3. μ-Carbonato-κ(4) O,O':O',O''-bis-{[2'-(di-tert-butyl-phosphan-yl)biphenyl-2-yl-κ(2) P,C (1)]palladium(II)} dichloro-methane monosolvate.

    Science.gov (United States)

    Muller, Alfred; Holzapfel, Cedric W

    2012-12-01

    The title compound, [(μ2-CO3){Pd(P(t-C4H9)2(C12H8)}2]·CH2Cl2, the first CO3-bridged palladium dimer complex reported to date, was obtained while preparing the Pd(0) complex with (2-biphen-yl)P( (t) Bu)2. In the crystal, each palladium dimer is accompanied by a dichloro-methane solvent mol-ecule. Coordination of the carbonate and chelated phosphane ligands gives distorted square-planar environments at the Pd atoms. Important geometrical parameters include Pd-P(av.) = 2.2135 (4) Å, Pd-C(av.) = 1.9648 (16) Å and P-Pd-C = 84.05 (5) and 87.98 (5)°, and O-Pd-O' = 60.56 (4) and 61.13 (4)°. Bonding with the carbonate O atoms shows values of 2.1616 (11) and 2.1452 (11) Å for the Pd-O-Pd bridge, whereas other Pd-O distances are slightly longer at 2.2136 (11) and 2.1946 (11) Å. One of the tert-butyl groups is disordered over two set of sites with an occupancy ratio of 0.723 (6):0.277 (6). Weak C-H⋯O interactions are observed propagating the molecules along the [100] direction.

  4. Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36

    DEFF Research Database (Denmark)

    Ettrup, Anders; Svarer, Claus; McMahon, Brenda

    2016-01-01

    INTRODUCTION: [(11)C]Cimbi-36 is a recently developed serotonin 2A (5-HT2A) receptor agonist positron emission tomography (PET) radioligand that has been successfully applied for human neuroimaging. Here, we investigate the test-retest variability of cerebral [(11)C]Cimbi-36 PET and compare [(11)C...... test-retest variability in [(11)C]Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [(18)F]altanserin. Regional differences in the brain distribution of [(11)C]Cimbi-36 and [(18)F]altanserin were assessed with a correlation of regional binding measures...... and with voxel-based analysis. RESULTS: Test-retest variability of [(11)C]Cimbi-36 non-displaceable binding potential (BPND) was consistently correlation between regional...

  5. (Z-N-[3-(4-Bromobenzoyl-1,3-thiazolidin-2-ylidene]cyanamide

    Directory of Open Access Journals (Sweden)

    Ling Xu

    2010-12-01

    Full Text Available In the title compound, C11H8BrN3OS, the dihedral angle between the benzene and thiazolidine rings is 63.4 (2°. Intermolecular C—H...N interactions help to stabilize the crystal structure.

  6. Vibrational spectra and structure of icosahedral anion of monocarba-closo-dodecaborane [CB11H12]- and its nido-derivative: [CB10H13]-

    International Nuclear Information System (INIS)

    Kononova, E.G.; Bukalov, S.S.; Lejtes, L.A.; Lysenko, K.A.; Ol'shevskaya, V.A.

    2003-01-01

    Raman and IR spectra of cesium salts of monocarborane anions [closo-CB 11 H 12 ] - and [nido-CB 10 H 13 ] - were recorded, assignment of frequencies being provided. Quantum-chemical calculation of geometry of the closo-polyhedrons [B 12 H 12 ] 2- and [CB 11 H 12 ] - along with that of frequencies and forms of normal vibrations of the latter was made. Comparison of structural and spectral characteristics in the series of isoelectronic closo-polyhedrons [B 12 H 12 ] 2- , [CB 11 H 12 ] - and p-C 2 B 10 H 12 , as well as those of the closo- and nido structures, was made [ru

  7. [(6-Methyl-2-pyridylmethyl(2-pyridylmethylamine][(2-pyridylmethylamine]copper(II bis(perchlorate

    Directory of Open Access Journals (Sweden)

    Ray J. Butcher

    2008-01-01

    Full Text Available The title compound, [Cu(C6H8N2(C13H15N3](ClO42, is a mixed ligand complex with the CuII atom coordinated by (6-methyl-2-pyridylmethyl(2-pyridylmethylamine, acting as a tridentate ligand, and 2-(2-aminomethylpyridine, as a bidentate ligand, leading to an N5 square-pyramidal geometry. The amine H atoms are involved in hydrogen bonding to the perchlorate O atoms and there are extensive but weak intermolecular C—H...O interactions in the crystal structure. The perchlorate ions are each disordered over two positions, with site occupancies of 0.601 (8:0.399 (8 and 0.659 (11:0.341 (11.

  8. Effect of TiC addition on surface oxidation behavior of SKD11 tool steel composites

    Science.gov (United States)

    Cho, Seungchan; Jo, Ilguk; Kim, Heebong; Kwon, Hyuk-Tae; Lee, Sang-Kwan; Lee, Sang-Bok

    2017-09-01

    Titanium carbide (TiC) reinforced tool steel matrix composites were successfully fabricated by a liquid pressing infiltration process and research was subsequently conducted to investigate the composites' oxidation resistance. The mass gain of the tested TiC-SKD11 composite held at 700 °C for 50 h in an air environment decreased by about 60%, versus that of the SKD11, which indicates improved oxidation resistance. Improved oxidation resistance of the TiC-SKD11 composite originates from uniformly reinforced TiC, with a phase transition to thermodynamically stable, volume-expanded TiO2.

  9. Genetic variants in ATM, H2AFX and MRE11 genes and susceptibility to breast cancer in the polish population.

    Science.gov (United States)

    Podralska, Marta; Ziółkowska-Suchanek, Iwona; Żurawek, Magdalena; Dzikiewicz-Krawczyk, Agnieszka; Słomski, Ryszard; Nowak, Jerzy; Stembalska, Agnieszka; Pesz, Karolina; Mosor, Maria

    2018-04-20

    DNA damage repair is a complex process, which can trigger the development of cancer if disturbed. In this study, we hypothesize a role of variants in the ATM, H2AFX and MRE11 genes in determining breast cancer (BC) susceptibility. We examined the whole sequence of the ATM kinase domain and estimated the frequency of founder mutations in the ATM gene (c.5932G > T, c.6095G > A, and c.7630-2A > C) and single nucleotide polymorphisms (SNPs) in H2AFX (rs643788, rs8551, rs7759, and rs2509049) and MRE11 (rs1061956 and rs2155209) among 315 breast cancer patients and 515 controls. The analysis was performed using high-resolution melting for new variants and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for recurrent ATM mutations. H2AFX and MRE11 polymorphisms were analyzed using TaqMan assays. The cumulative genetic risk scores (CGRS) were calculated using unweighted and weighted approaches. We identified four mutations (c.6067G > A, c.8314G > A, c.8187A > T, and c.6095G > A) in the ATM gene in three BC cases and two control subjects. We observed a statistically significant association of H2AFX variants with BC. Risk alleles (the G of rs7759 and the T of rs8551 and rs2509049) were observed more frequently in BC cases compared to the control group, with P values, odds ratios (OR) and 95% confidence intervals (CIs) of 0.0018, 1.47 (1.19 to 1.82); 0.018, 1.33 (1.09 to 1.64); and 0.024, 1.3 (1.06 to 1.59), respectively. Haplotype-based tests identified a significant association of the H2AFX CACT haplotype with BC (P ATM gene to the development of breast cancer needs further detailed study.

  10. Phase Transition Enthalpy Measurements of Organic and Organometallic Compounds and Ionic Liquids. Sublimation, Vaporization, and Fusion Enthalpies from 1880 to 2015. Part 2. C11-C192

    Science.gov (United States)

    Acree, William; Chickos, James S.

    2017-03-01

    The second part of this compendium concludes with a collection of phase change enthalpies of organic molecules inclusive of C11-C192 reported over the period 1880-2015. Also included are phase change enthalpies including fusion, vaporization, and sublimation enthalpies for organometallic, ionic liquids, and a few inorganic compounds. Paper I of this compendium, published separately, includes organic compounds from C1 to C10 and describes a group additivity method for evaluating solid, liquid, and gas phase heat capacities as well as temperature adjustments of phase changes. Paper II of this compendium also includes an updated version of a group additivity method for evaluating total phase change entropies which together with the fusion temperature can be useful in estimating total phase change enthalpies. Other uses include application in identifying potential substances that either form liquid or plastic crystals or exhibit additional phase changes such as undetected solid-solid transitions or behave anisotropically in the liquid state.

  11. 1,5-Bis(2,5-dimethyl-1H-pyrrol-1-ylnaphthalene

    Directory of Open Access Journals (Sweden)

    A. C. Santos

    2009-11-01

    Full Text Available In the title compound, C22H22N2, the asymmetric unit contains one half-molecule. A crystallographic inversion centre is located at the mid-point of the bond common to both rings, in the central naphthalene unit. Quantum-mechanical ab initio calculations on the isolated molecule showed that the minimum energy configuration occurs when the naphthalene ring system and the pyrrolyl groups deviate only slightly from perpendicularity. In the crystal, due to the effects of crystal packing, the molecule deviates by approximately 4° from the a priori expected ideal value of 90° [C—C—N—C torsion angle = 86.11 (15°].

  12. (-)-N-[11C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D2 receptors

    International Nuclear Information System (INIS)

    Hwang, Dah-Ren; Kegeles, Lawrence S.; Laruelle, Marc

    2000-01-01

    Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [ 11 C]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[ 11 C]NPA was prepared by reacting norapomorphine with [ 11 C]propionyl chloride and a lithium aluminum hydride reduction. [ 11 C]Propionyl chloride was prepared by reacting [ 11 C]CO 2 with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[ 11 C]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700±1900 mCi/μmol ( N=7; ranged 110-5200 mCi/μmol at EOS). Rodent biodistribution studies showed high uptake of [ 11 C](-)-NPA in D 2 receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3. (-)-[ 11 C]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions ( N=4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86±0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection. The result demonstrated the existence of specific binding of this new tracer to the D 2 receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D 2 agonist. (-)-[ 11 C]NPA is a promising new D 2 agonist PET tracer for probing D 2 receptors in vivo using PET

  13. (-)-N-[(11)C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors.

    Science.gov (United States)

    Hwang, D R; Kegeles, L S; Laruelle, M

    2000-08-01

    Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [(11)C]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[(11)C]NPA was prepared by reacting norapomorphine with [(11)C]propionyl chloride and a lithium aluminum hydride reduction. [(11)C]Propionyl chloride was prepared by reacting [(11)C]CO(2) with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[(11)C]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700+/-1900 mCi/micromol ( N=7; ranged 110-5200 mCi/micromol at EOS). Rodent biodistribution studies showed high uptake of [(11)C](-)-NPA in D(2) receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3. (-)-[(11)C]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions ( N=4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86+/-0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection. The result demonstrated the existence of specific binding of this new tracer to the D(2) receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D(2) agonist. (-)-[(11)C]NPA is a promising new D(2) agonist PET tracer for probing D(2) receptors in vivo using PET.

  14. Aqua{N-[1-(2-oxidophenylethylidene]-l-serinato}copper(II monohydrate

    Directory of Open Access Journals (Sweden)

    Qin-Long Peng

    2009-12-01

    Full Text Available In the title compound, [Cu(C11H11NO4(H2O]·H2O, each CuII ion is four-coordinated by one N and two O atoms from the tridentate Schiff base ligand, and by one O atom from the coordinated water molecule in a distorted square-planar geometry. Intermolecular O—H...O hydrogen bonds link complex molecules and solvent water molecules into flattened columns propagated in [100].

  15. Synthesis of the sup 11 C-labelled. beta. -adrenergic receptor ligands atenolol, metoprolol and propanolol

    Energy Technology Data Exchange (ETDEWEB)

    Antoni, G.; Ulin, J.; Laangstroem, B. (Uppsala Univ. (Sweden). Dept. of Organic Chemistry)

    1989-01-01

    The {sup 11}C-labelled {beta}-adrenergic receptor ligands atenolol 1, metoprolol 2 and propranolol 3 have been synthesized by an N-alkylation reaction using (2-{sup 11}C)isopropyl iodide. The labelled isopropyl iodide was prepared in a one-pot reactor system from ({sup 11}C)carbon dioxide and obtained in 40% radiochemical yield within 14 min reaction time. The total reaction times for compounds 1-3, counted from the start of the isopropyl iodide synthesis and including purification were 45-55 min. The products were obtained in 5-15% radiochemical yields and with radiochemical purities higher than 98%. The specific activity ranged from 0.4 to 4 GBq/{mu}mol. In a typical experiment starting with 4 GBq around 75 MBq of product was obtained. (author).

  16. Induction of apoptosis by 3-amino-6-(3-aminopropyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline via modulation of MAPKs (p38 and c-Jun N-terminal kinase) and c-Myc in HL-60 human leukemia cells.

    Science.gov (United States)

    Park, Eun-Jung; Kiselev, Evgeny; Conda-Sheridan, Martin; Cushman, Mark; Pezzuto, John M

    2012-03-23

    Recently, we reported that 3-amino-6-(3-aminopropyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (AM6-36), sharing structural similarity with naturally occurring isoquinolines, induced activities mediated by retinoid X receptor (RXR) response element accompanied by antiproliferative effects on breast cancer cells. To further characterize the biologic potential of AM6-36, we currently report studies conducted with HL-60 human leukemia cells. AM6-36 significantly inhibited cellular proliferation in a dose- and time-dependent manner with an IC(50) value of 86 nM. When evaluated at low test concentrations (≤0.25 μM), AM6-36 induced arrest in the G2/M phase of the cell cycle. At higher concentrations (1 and 2 μM), the response shifted to apoptosis, which was consistent with the effect of AM6-36 on other apoptotic signatures including an increase of apoptotic annexin V(+) 7-AAD(-) cells, loss of mitochondrial membrane potential, induction of poly(ADP-ribose) polymerase cleavage, and activation of several caspases. These apoptotic effects are potentially due to up-regulation of p38 MAPK and JNK phosphorylation and down-regulation of c-Myc oncogene expression. Taken together, AM6-36 might serve as an effective anticancer agent by inducing G2/M cell cycle arrest and apoptosis through the activation of MAPKs and inhibition of c-Myc.

  17. Whole-body distribution and radiation dosimetry of the dopamine transporter radioligand [11C]PE2I in healthy volunteers

    International Nuclear Information System (INIS)

    Ribeiro, Maria-Joao; Ricard, Marcel; Lievre, Marie-Angele; Bourgeois, Sandrine; Emond, Patrick; Gervais, Philippe; Dolle, Frederic; Syrota, Andre

    2007-01-01

    Introduction: This study reports on the biodistribution and radiation dosimetry of a cocaine analog, the (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy-3β-(4'-tolyl)nortropane (PE2I), labeled with carbon 11 ([ 11 C]PE2I). [ 11 C]PE2I is used in positron emission tomography (PET) for examination of the dopamine neuronal transporter (DAT). DAT radioligands are often used to evaluate the progression of Parkinson's disease or the efficiency of neuroprotective therapeutics, and, typically, these studies required several successive PET scans. Methods: In three healthy male volunteers, whole-body scans were performed up to 2 h following intravenous injection of 321±6 MBq of [ 11 C]PE2I. For each subject, regions of interest were defined over all visible organs to generate time-activity curves and calculate the percentage of injected activity. Time-activity data were fitted to a monoexponential model, as an uptake phase followed by a mono-exponential washout, or bi-exponential model to obtain residence times. With the use of the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses. Results: Blood pressure and ECG findings remained unchanged after radioligand injection. The primary route of clearance was renal. Ten minutes after injection, high activities were observed in the kidneys, urinary-bladder, stomach, liver, salivary glands and brain. The urine bladder wall, stomach and liver received the highest absorbed doses. The average effective dose of [ 11 C]PE2I was estimated to be 6.4±0.6 μSv/MBq. Conclusion: The amount of [ 11 C]PE2I required for adequate DAT PET imaging results in an acceptable effective dose equivalent permitting two or three repeated cerebral PET studies, with the injection of 222 MBq for each study

  18. Radiosynthesis of [11C]glyburide for in vivo imaging of BCRP function with PET

    International Nuclear Information System (INIS)

    Kuhnast, B.; Damont, A.L.; Tournier, N.; Saba, W.; Valette, H.; Bottlaender, M.; Dolle, F.

    2011-01-01

    Complete text of publication follows: Objectives: The human breast cancer resistance protein (BCRP/ABCG2) belongs to the ABC-transporter super-family in which P-gp (MDR1/ABCB1) is probably the most emblematic and best known member. BCRP, which was initially discovered in multidrug resistant breast cancer cell lines, is also highly expressed in numerous tissues e.g. the blood-brain barrier (BBB). BCRP confers upon these tissues resistance to chemotherapeutic agents but also transports drugs and xenobiotics thus participating to the ADME processes although the biochemical mechanisms remain largely unknown to date. The hypoglycaemic sulfonylurea glyburide (glibenclamide) has been described as a specific substrate of BCRP in vitro and in vivo. Its isotopic labelling with the positron emitter carbon-11 (20.4 min) would provide a valuable tool to study in vivo with PET the BCRP transport activity. Herein are reported the synthesis of desmethyl-glyburide (2), as precursor, as well as the preparation of [ 11 C]glyburide ([ 11 C]-1) using [ 11 C]methyl triflate as radio-methylation agent. Methods: Chemistry: Desmethyl-glyburide (2), as precursor for [ 11 C]labelling, was obtained in one chemical step by treating glyburide (1) with a 1 M solution of BBr 3 (4 eq.) in dichloromethane at low temperature (-90 C to - 20 C). Radiochemistry: Carbon-11 labeling of glyburide (1) was performed using a TRACERLab FX-C Pro synthesizer (GEMS) and comprised (1) trapping at -10 C of [ 11 C]MeOTf in acetone (0.3 mL) containing the precursor 2 (0.5-0.8 mg) and aq. 3N NaOH (5 μL); (2) heating at 110 C for 2 min; (3) dilution in 1.0 mL of the HPLC mobile phase and purification using semi-preparative reversed-phase HPLC (Waters Symmetry R C-18 - eluent: CH 3 CN / H 2 O / TFA: 45 / 55 / 0.1 (v:v:v) - flow rate: 5 mL/min - detection at 254 nm) and (4) SepPak R Plus C-18-based formulation for i.v. injection. The measurement of log P and log D 7.4 was performed using the shaked flask method

  19. (meso-5,7,7,12,14,14-Hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-dienenickel(II dibromide dihydrate

    Directory of Open Access Journals (Sweden)

    Yonghong Lu

    2010-10-01

    Full Text Available The asymmetric unit of the title compound, [Ni(C16H32N4]Br2·2H2O, consists of one half [Ni(C16H32N4]2+ cation, one Br− anion and one water molecule of crystallization. The NiII ion lies on an inversion centre in a square-planar environment formed by the four macrocyclic ligand N atoms. In the crystal structure, the cations, anions and water molecules are linked via intermolecular N—H...Br and O—H...Br hydrogen bonds, forming discrete chains with set-graph motif D(2D22(7D21(3D32(8. The water molecules and Br− ions are linked with set-graph motif R42(8.

  20. 11C-radioisotope study of methanol co-reaction with ethanol over Ni-MCM-41 silica-alumina and Ni-alumina

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Kovacs, Z.; Tsoncheva, T.; Kumar, N.; Murzin, D.Yu.

    2009-01-01

    Complete text of publication follows. The Ni modifies the properties of acidic alumina and light acidic MCM-41 silica-alumina supports. The radioisotopic method is a suitable tool for distinction of the 11 Cradioisotopic methanol and its co-derivates from derivates of non-radioactive ethanol on these catalysts. Experimental. The Ni/A l 2O 3 (5 wt % Ni) is commercially available while H-MCMN-41 (Si/Al=20) and Ni-ion-exchanged MCM-41 silica-alumina (5 wt % Ni) were prepared and characterized in previous works. Before catalysis the Ni/Al 2 O 3 and Ni-MCM-41 were pre-reduced. The 11 C-methanol was formed by a radiochemical process from 11 C-carbon dioxide produced at cyclotron (T 1/2 = 20.4 min). The mixture of equivalent volume of radioactive methanol and non-radioactive ethanol was introduced into glass tube micro-flow reactor at ambient temperature. After adsorption, the valves were closed and the catalyst was heated up to the required temperatures. The desorption rate of the remaining 11 C-derivatives on catalysts were continuously followed by radiodetectors and the derivatives of methanol with ethanol were analyzed by Radio/FID-gas chromatography (FID is coupled on-line with a radiodetector). The ethanol and its derivates were identified by FID while the 11 C-methanol and its co-derivates (with ethanol) were detected by both of FID and radiodetector. Results The 11 C-dimethyl ether was the common product of the single 11 C-methanol transformation on H-MCM-41, Ni-MCM-41 and Ni- Al 2 O 3 at low temperature (200-280 degC) due to middle strong acid sites. At higher temperature (280-350 degC), the dimethyl ether and hydrocarbons were the dominant products on H-MCM-41 while dimethyl ether selectivity decreased on Ni-alumina and Ni-MCM-41 in favor of methane. The selectivities of methanol to formaldehyde and methane were the highest on Ni-MCM-41. During co-reaction of 11 C-methanol with non-radioactive ethanol, the 11 C-labeled coethers, namely 11 C-methyl ethyl ether

  1. Radiosynthesis and in vivo evaluation of N-[{sup 11}C]methylated imidazopyridineacetamides as PET tracers for peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sekimata, Katsuhiko [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Hatano, Kentaro [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)], E-mail: hatanok@nils.go.jp; Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192 Japan (Japan); Abe, Junichiro [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192 Japan (Japan); Biggio, Giovanni; Serra, Mariangela [Department of Experimental Biology, University of Cagliari, Cagliari 09100 (Italy); Laquintana, Valentino; Denora, Nunzio; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano [Pharmaco-Chemistry Department, University of Bari, Bari 70125 (Italy); Ito, Kengo [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)

    2008-04-15

    Imidazopyridineacetoamide 5-8, a series of novel and potentially selective peripheral benzodiazepine receptor (PBR) ligands with affinities comparable to those of known PBR ligands, was investigated. Radiosyntheses of [{sup 11}C]5, 6, 7 or 8 was accomplished by N-methylation of the corresponding desmethyl precursors with [{sup 11}C]methyl iodide in the presence of NaH in dimethylformamide (DMF), resulting in 25% to 77% radiochemical yield and specific activitiy of 20 to 150 MBq/nmol. Each of the labeled compounds was injected in ddY mice, and the radioactivity and weight of dissected peripheral organs and brain regions were measured. Organ distribution of [{sup 11}C]7 was consistent with the known PBR distribution. Moreover, [{sup 11}C]7 showed the best combination of brain uptake and PBR binding, leading to its high retention in the olfactory bulb and cerebellum, areas where PBR density is high in mouse brain. Coinjection of PK11195 or unlabeled 7 significantly reduced the brain uptake of [{sup 11}C]7. These results suggest that [{sup 11}C]7 could be a useful radioligand for positron emission tomography imaging of PBRs.

  2. Synthesis, β-haematin inhibition, and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11.

    Science.gov (United States)

    Wang, Ning; Wicht, Kathryn J; Imai, Kento; Wang, Ming-Qi; Anh Ngoc, Tran; Kiguchi, Ryo; Kaiser, Marcel; Egan, Timothy J; Inokuchi, Tsutomu

    2014-05-01

    A series of indolo[3,2-c]quinolines were synthesized by modifying the side chains of the ω-aminoalkylamines at the C6 position and introducing substituents at the C2 position, such as F, Cl, Br, Me, MeO and NO2, and a methyl group at the N11 position for an SAR study. The in vitro antiplasmodial activities of the derivative agents against two different strains (CQS: NF54 and CQR: K1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that compounds 6k and 6l containing the branched methyl groups of 3-aminopropylamino at C6 with a Cl atom at C2 exhibited a very low cytotoxicity with IC50 values above 4000 nM, high antimalarial activities with IC50 values of about 11 nM for CQS (NF54), IC50 values of about 17 nM for CQR (K1), and RI resistance indices of 1.6. Furthermore, the compounds were tested for β-haematic inhibition, and QSAR revealed an interesting linear correlation between the biological activity of CQS (NF54) and three contributing factors, namely solubility, hydrophilic surface area, and β-haematin inhibition for this series. In vivo testing of 6l showed a reduction in parasitaemia on day 4 with an activity of 38%. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Biodistribution and radiation dosimetry of [{sup 11}C]DASB in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Belanger, Marie-Jose [Department of Psychiatry, Columbia University College of Physicians and Surgeons New York, NY 10032 (United States); Division of Brain Imaging, Department of Neuroscience, New York State Pyschiatric Institute, New York, NY 10032 (United States); Simpson, Norman R. [Department of Radiology, Columbia University College of Physicians and Surgeons and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Wang, Theodore [Department of Radiology, Columbia University College of Physicians and Surgeons and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Division of Brain Imaging, Department of Neuroscience, New York State Pyschiatric Institute, New York, NY 10032 (United States)] [and others

    2004-11-01

    Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [{sup 11}C]DASB ([{sup 11}C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [{sup 11}C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183{+-}5 MBq/2.3{+-}1.0 nmol of [{sup 11}C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6x10{sup -2} mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [{sup 11}C]DASB. In the United States, the absorbed dose to the lungs would limit [{sup 11}C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female.

  4. Pharmacophore Modeling and in Silico/in Vitro Screening for Human Cytochrome P450 11B1 and Cytochrome P450 11B2 Inhibitors.

    Science.gov (United States)

    Akram, Muhammad; Waratchareeyakul, Watcharee; Haupenthal, Joerg; Hartmann, Rolf W; Schuster, Daniela

    2017-01-01

    Cortisol synthase (CYP11B1) is the main enzyme for the endogenous synthesis of cortisol and its inhibition is a potential way for the treatment of diseases associated with increased cortisol levels, such as Cushing's syndrome, metabolic diseases, and delayed wound healing. Aldosterone synthase (CYP11B2) is the key enzyme for aldosterone biosynthesis and its inhibition is a promising approach for the treatment of congestive heart failure, cardiac fibrosis, and certain forms of hypertension. Both CYP11B1 and CYP11B2 are structurally very similar and expressed in the adrenal cortex. To facilitate the identification of novel inhibitors of these enzymes, ligand-based pharmacophore models of CYP11B1 and CYP11B2 inhibition were developed. A virtual screening of the SPECS database was performed with our pharmacophore queries. Biological evaluation of the selected hits lead to the discovery of three potent novel inhibitors of both CYP11B1 and CYP11B2 in the submicromolar range (compounds 8 - 10 ), one selective CYP11B1 inhibitor (Compound 11 , IC 50 = 2.5 μM), and one selective CYP11B2 inhibitor (compound 12 , IC 50 = 1.1 μM), respectively. The overall success rate of this prospective virtual screening experiment is 20.8% indicating good predictive power of the pharmacophore models.

  5. Pharmacophore Modeling and in Silico/in Vitro Screening for Human Cytochrome P450 11B1 and Cytochrome P450 11B2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Muhammad Akram

    2017-12-01

    Full Text Available Cortisol synthase (CYP11B1 is the main enzyme for the endogenous synthesis of cortisol and its inhibition is a potential way for the treatment of diseases associated with increased cortisol levels, such as Cushing's syndrome, metabolic diseases, and delayed wound healing. Aldosterone synthase (CYP11B2 is the key enzyme for aldosterone biosynthesis and its inhibition is a promising approach for the treatment of congestive heart failure, cardiac fibrosis, and certain forms of hypertension. Both CYP11B1 and CYP11B2 are structurally very similar and expressed in the adrenal cortex. To facilitate the identification of novel inhibitors of these enzymes, ligand-based pharmacophore models of CYP11B1 and CYP11B2 inhibition were developed. A virtual screening of the SPECS database was performed with our pharmacophore queries. Biological evaluation of the selected hits lead to the discovery of three potent novel inhibitors of both CYP11B1 and CYP11B2 in the submicromolar range (compounds 8–10, one selective CYP11B1 inhibitor (Compound 11, IC50 = 2.5 μM, and one selective CYP11B2 inhibitor (compound 12, IC50 = 1.1 μM, respectively. The overall success rate of this prospective virtual screening experiment is 20.8% indicating good predictive power of the pharmacophore models.

  6. Evaluation of the kappa-opioid receptor-selective tracer [11C]GR103545 in awake rhesus macaques

    International Nuclear Information System (INIS)

    Schoultz, Bent W.; Hjornevik, Trine; Willoch, Frode; Marton, Janos; Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro; Aarstad, Erik; Drzezga, Alexander; Matsunari, Ichiro; Henriksen, Gjermund

    2010-01-01

    The recent development in radiosynthesis of the 11 C-carbamate function increases the potential of [ 11 C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (κ-OR) with PET. In the present study, [ 11 C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [ 11 C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [ 11 C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for κ-OR (K i = 0.02 ±0.01 nM) with excellent selectivity over μ-OR (6 x 10 2 -fold) and δ-OR (2 x 10 4 -fold). PET imaging revealed a volume of distribution (V T ) pattern consistent with the known distribution of κ-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [ 11 C]GR103545 is selective for κ-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

  7. [14C]-radiolabeling of {[trans-(8β)]-6-methyl-1-(1-methylethyl) ergoline-8-carboxylic acid, 4-methoxycyclohexyl ester (Z)-2-buteneidioate (1:1)}

    International Nuclear Information System (INIS)

    Marzoni, G.; Wheeler, W.J.; Garbrecht, W.L.

    1988-01-01

    The 5HT 2 -receptor antagonist, [ 14 C]-labeled brace[trans-(8β)]-6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid, 4-methoxycyclohexyl ester (Z)-2-butenedioate (1:1)brace (LY281067) was synthesized from unlabeled 6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid. The [ 14 C] label was introduced into the carboxyl group attached to the 8 position of the ergoline nucleus. This site is stable to metabolism. The synthesis involves removal of an unlabeled carboxyl group and subsequent reinsertion of a [ 14 C]-labeled carboxyl group into the same position. The radiolabel is not introduced until near the end of the synthesis which allows for ease of handling and scale-up of intermediates. (author)

  8. Synthesis and in-vivo evaluation of C-11 p-PVP-MEMA as a PET radioligand for imaging nicotinic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Paine, T.; Kassiou, M. [Univ Sydney, Sch Chem, Sydney, NSW 2006 (Australia); Dolle, F.; Langle, S.; Roger, G.; Lagnel-de Bruin, B.; Hinnen, F.; Valette, H.; Bottlaender, M. [CEA, Serv Hosp Frederic Joliot, Inst Imagerie Biomed, F-91401 Orsay (France); Fulton, R.R.; Henderson, D.J. [Royal Prince Alfred Hosp, Dept PET and Nucl Med, Camperdown, NSW 2050 (Australia); Coster, M.J. [Griffith Univ, Eskitis Inst Cell and Mol Therapies, Nathan, Qld 4121 (Australia); Kassiou, M. [Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW2006 (Australia); Brain and Mind Res Inst, Camperdown, NSW2050 (Australia)

    2008-07-01

    Within the class of (4-pyridinyl)vinyl-pyridines developed by Abbott laboratories as potent neuronal nicotinic acetylcholine receptor ligands, p-PVP-MEMA ({l_brace}oro-5-((E)-2-pyridin-4-yl-vinyl) pyridin-3-yloxy]-1-methylethyl{r_brace} is the lead compound of a novel series that do not display the traditional nicotinic-like pyrrole-ring but still possessing high sub-nanomolar affinity (K-i 0.077 nm-displacement of [H-3](-)cytisine from whole rat brain synaptic membranes). In the present study, p-PVP-MEMA and its nor-derivative ({l_brace}oro-5-((E)-2-pyridin-4- yl-vinyl) pyridin-3-yloxy]-1-methylethyl{r_brace} as precursor for labelling with the short-lived positron-emitter carbon-11 (T{sub 1/2} = 20.4 min) were synthesized in 10 chemical steps from 2-hydroxy-5-nitropyridine and Boc-D-alanine. N-Alkylation of nor-p-PVP-MEMA with [C-11] methyl iodide afforded [C-11]p-PVP-MEMA ({>=} 98% radiochemically pure, specific activity of 86.4 GBq {mu} mol{sup -1}) in 2% (non-decay corrected and non-optimized) radiochemical yield, in 34 min (including HPLC purification and formulation). Preliminary positron emission tomography PET) results obtained in a Papio hamadryas baboon showed that [C-11] p-PVP-MEMA is not a suitable PET-radioligand. (authors)

  9. 1,1′-(Ethane-1,2-diylbis(indoline-2,3-dione

    Directory of Open Access Journals (Sweden)

    Yao Wang

    2010-07-01

    Full Text Available The molecule of the title compound, C18H12N2O4, is situated on a crystallographic centre of symmetry. The molecule has a zigzag structure, with two parallel symmetry-related indoline-2,3-dione fragments linked by an ethylene group at each N atom. In the crystal, the molecules stack in columns along the b axis. There are two such columns in the structure. The molecules within each column are parallel; however, the molecules in the two columns differ in the respective orientation of the indoline-2,3-dione fragments. In one column, they are approximately parallel to (112, while in the other they are approximately parallel to (overline{1}12. The interplanar angle between the indoline-2,3-dione fragments in the two columns is 80.83 (3°. The molecules within each column are related by mutual displacement of their centres of symmetry, that is (0, ±1/2, ±1/2. The packing between the molecules is provided by weak interactions only, viz. C—H...O hydrogen bonds and π–π [centroid–centroid distance = 3.8745 (8 Å] and C=O...π interactions.

  10. 2-{[4-(1,3-Benzothiazol-2-ylphenyl](methylamino}acetic acid

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2009-11-01

    Full Text Available In the title compound, C16H14N2O2S, the dihedral angle between the benzothiazole ring system and benzene ring is 3.11 (2°. In the crystal structure, intermolecular O—H...N hydrogen bonds link molecules into chains along [100] and these chains are, in turn, linked into a three-dimensional network via weak intermolecular C—H...O hydrogen bonds.

  11. 2-[(Prop-2-yn-1-ylamino]anilinium chloride

    Directory of Open Access Journals (Sweden)

    Abdelhanine Essaghouani

    2017-11-01

    Full Text Available The title compound, C9H11N2+·Cl−, is an anilinium chloride salt, in which the Car—N—C—C (ar = aromatic torsion angle is −84.95 (18°. In the crystal, a bilayer of cation–anion sheets runs parallel to (100, primarily through an extensive range of N—H...Cl hydrogen bonds. Weak offset π-stacking interactions between the benzene rings stack molecules along c.

  12. The synthesis of 5-[1-11C]ethyl barbiturates from labelled malonic esters

    International Nuclear Information System (INIS)

    Gee, A.; Laangstroem, B.

    1991-01-01

    The synthesis of [ 11 C]phenobarbital, [ 11 C]pentobarbital and[ 11 C]amobarbital labelled in the 5-[1- 11 C]ethyl position is reported. The malonic esters R- CH(CO 2 Et) 2 [R phenyl-, 1-methylbutyl-, and 3- methylbutyl- were alkylated with [1- 11 C]ethyl iodide prepared from [ 11 C]carbon dioxide. Ring closure of the 2-[1- 11 C]ethyl-labelled malonic esters with urea afforded 5-[1- 11 C]ethyl-phenobarbital,-phenobarbital, -pentobarbital and -amobarbital synthesis times of 42-47 min, counted from [ 11 C] carbon dioxide. In typical syntheses starting with 3 GBq pentobarbitol and (81 mCi) [ 11 C]carbon dioxide, 150-215 MBq (4-6 mCi) were produced in 25-30% decay corrected -amobarbital radiochemical yields with radiochemical purities greater than 98%. (author)

  13. A fast chemoenzymatic synthesis of [11C]-N5,N10-methylenetetrahydrofolate as a potential PET tracer for proliferating cells

    International Nuclear Information System (INIS)

    Saeed, Muhammad; Tewson, Timothy J.; Erdahl, Colbin E.; Kohen, Amnon

    2012-01-01

    Introduction: Thymidylate synthase and folate receptors are well-developed targets of cancer therapy. Discovery of a simple and fast method for the conversion of 11 CH 3 Ito[ 11 C]-formaldehyde ( 11 CH 2 O) encouraged us to label the co-factor of this enzyme. Preliminary studies conducted on cell lines have demonstrated a preferential uptake of [11- 14 C]-(R)-N 5 ,N 10 -methylene-5,6,7,8-tetrahydrofolate ( 14 CH 2 H 4 folate) by cancerous cell vs. normal cells from the same organ (Saeed M., Sheff D. and Kohen A. Novel positron emission tomography tracer distinguishes normal from cancerous cells. J Biol Chem 2011;286:33872–33878), pointing out 11 CH 2 H 4 folate as a positron emission tomography (PET) tracer for cancer imaging. Herein we report the synthesis of 11 CH 2 H 4 folate, which may serve as a potential PET tracer. Methods: In a remotely controlled module, methyl iodide ( 11 CH 3 I) was bubbled into a reaction vial containing trimethylamine N-oxide in N,N-Dimethylformamide (DMF) and heated to 70°C for 2 min. Formaldehyde ( 11 CH 2 O) formed after the completion of reaction was then mixed with a solution of freshly prepared tetrahydrofolate (H 4 folate) by using a fast chemoenzymatic approach to accomplish synthesis of 11 CH 2 H 4 folate. Purification of the product was carried out by loading the crude reaction mixture on a SAX cartridge, washing with water to remove unbound impurities and finally eluting with a saline solution. Results: The synthesis and purification of 11 CH 2 H 4 folate were completed within 5 min. High-performance liquid chromatography analysis of the product after SAX purification indicates that more than 90% of the radioactivity that was retained on the SAX cartridge was in 11 CH 2 H 4 folate, with minor ( 11 CH 2 O. Conclusion: We present a fast (∼5 min) synthesis and purification of 11 CH 2 H 4 folate as a potential PET tracer. The final product is received in physiologically compatible buffer (100 mM sodium phosphate, pH 7

  14. Hepatic metabolism of 11C-methionine and secretion of 11C-protein measured by PET in pigs

    DEFF Research Database (Denmark)

    Horsager, Jacob; Lausten, Susanne Bach; Bender, Dirk

    2017-01-01

    Hepatic amino acid metabolism and protein secretion are essential liver functions that may be altered during metabolic stress, e.g. after surgery. We wished to develop a dynamic liver PET method using the radiolabeled amino acid 11C-methionine to examine this question. Eleven 40-kg pigs were...... allocated to either laparotomy or pneumoperitoneum. 24 hours after surgery a 70-min dynamic PET scanning of the liver with arterial blood sampling was performed immediately after intravenous injection of 11C-methionine. Time course of arterial plasma 11C-methionine concentration was used as input function...

  15. Low-temperature heat capacities and thermodynamic properties of ethylenediammonium tetrachlorozincate chloride (C2H10N2)2(ZnCl4)Cl2

    International Nuclear Information System (INIS)

    He, Dong-Hua; Di, You-Ying; Wang, Bin; Dan, Wen-Yan; Tan, Zhi-Cheng

    2010-01-01

    The ethylenediammonium tetrachlorozincate chloride (C 2 H 10 N 2 ) 2 (ZnCl 4 )Cl 2 was synthesized. Chemical analysis, elemental analysis, and X-ray crystallography were applied to characterize the composition and crystal structure of the complex. Low-temperature heat capacities of the compound were measured by a precision automatic adiabatic calorimeter over the temperature range from T = 77-377 K. A polynomial equation of heat capacities as a function of the reduced temperature was fitted by a least square method. Based on the polynomial equation, the smoothed heat capacities and thermodynamic functions of the title compound relative to the standard reference temperature 298.15 K were calculated at intervals of 5 K. A thermochemical cycle was designed and the enthalpy change of the solid phase reaction of ethylenediamine dihydrochloride with zinc chloride was determined to be Δ r H m o =-(17.9±0.6)kJmol -1 by an isoperibol solution-reaction calorimeter. Finally, the standard molar enthalpy of formation of the title compound was derived to be Δ f H m o [(C 2 H 10 N 2 ) 2 (ZnCl 4 )Cl 2 ,s]=-(1514.4±2.7)kJmol -1 in accordance with Hess law.

  16. A Facile Synthesis of Pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine and Pyrido[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]triazine Bearing a Thiophene Moiety

    Directory of Open Access Journals (Sweden)

    Tilal Elsaman

    2013-01-01

    Full Text Available Pyridinone derivative 8 was synthesized and transformed into the respective chloropyridine 9, which was allowed to react with hydrazine hydrate to afford pyrazolo[3,4-b]pyridin-3-amine derivative 11. Compound 11 was used as a key intermediate for a facile synthesis of the title compounds 14, 15, 17, 21a,b, and 24a–c where the reaction of 11 with some 1,3-dielecrophiles resulted in the formation of pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidines 14, 15, and 17, whereas diazotization of compound 11 gave the respective diazonium salt 18 which was coupled with some active methylene-containing compounds to give the corresponding hydrazones 19a,b and 22a–c. Cyclization of the latter hydrazones yielded the pyrido[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]triazines 21a,b and 24a–c, respectively.

  17. Crystal structure of mer-tris{2,6-difluoro-3-[5-(2-fluorophenylpyridin-2-yl-κN]pyridin-4-yl-κC4}iridium(III dichloromethane hemisolvate n-hexane hemisolvate

    Directory of Open Access Journals (Sweden)

    Youngjin Kang

    2017-12-01

    Full Text Available The asymmetric unit of the title compound, [Ir(C17H11F2N23]·0.5CH3(CH24CH3·0.5CH2Cl2, comprises one IrIII atom, three 2,6-difluoro-3-[5-(2-fluorophenylpyridin-2-yl]pyridin-4-yl ligands and half each of an n-hexane and a dichloromethane solvent molecule located about crystallographic inversion centres. The IrIII atom displays a distorted octahedral coordination geometry, having three C,N-chelating 2,6-difluoro-3-[5-(2-fluorophenylpyridin-2-yl]pyridin-4-yl ligands arranged in a meridional manner. The IrIII ion lies almost in the equatorial plane [deviation = 0.0069 (15 Å]. The average distance [2.041 (3 Å] of Ir—C bonds is slightly shorter than that [2.076 (3 Å] of Ir—N bonds. A variety of intra- and intermolecular C—H...F and C—H...π hydrogen bonds, as well as intermolecular C—F...π interactions, contribute to the stabilization of the molecular and crystal structures, and result in the formation of a two-dimensional network parallel to the ab plane. No interactions between n-hexane solvent molecules and the other components in the title compound are observed.

  18. Synthesis and evaluation of [11C]Cimbi-806 as a potential PET ligand for 5-HT7 receptor imaging

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Hansen, Hanne Demant; Ettrup, Anders Janusz

    2012-01-01

    )-N,N-dimethylethanamine ([(11)C]Cimbi-806) as a radioligand for imaging brain 5-HT(7) receptors with positron emission tomography (PET). Precursor and reference compound was synthesized and subsequent (11)C-labelling with [(11)C]methyltriflate produced [(11)C]Cimbi-806 in specific activities ranging from 50 to 300 GBq...... of appropriate in vivo blocking with a 5-HT(7) receptor selective compounds renders the conclusion that [(11)C]Cimbi-806 is not an appropriate PET radioligand for imaging the 5-HT(7) receptor in vivo....

  19. The balancing act of transcription factors C-1-1 and Runx2 in articular cartilage development

    International Nuclear Information System (INIS)

    Iwamoto, Masahiro; Koyama, Eiki; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio

    2005-01-01

    In previous studies we found that the ets transcription factor C-1-1 is involved in articular chondrocyte development, and we and others found that the transcription factor Runx2 is required for growth plate chondrocyte maturation and ossification. We determined here whether the two factors exert reciprocal influences on their expression and function and in so doing, steer chondrocyte developmental paths. Virally driven Runx2 over-expression in cultured chick chondrocytes did indeed lead to decreased C-1-1 expression, accompanied by decreased expression of articular cartilage marker tenascin-C, decreased proliferation, and increased expression of maturation marker collagen X. In good agreement, over-expression of a dominant-negative Runx2 form had opposite phenotypic consequences. When C-1-1 itself was over-expressed in chondrocytes already undergoing maturation, maturation was halted and the cells became small, rich in tenascin-C, and mitotically quite active. To extend these observations, we misexpressed C-1-1 in mouse cartilage and found that it caused a severe inhibition of chondrocyte maturation and widespread tenascin-C expression. In sum, C-1-1 and Runx2 do influence their respective expression patterns. The factors are powerful chondrocyte regulators and their functional interrelationships may be important for steering the cells toward alternative developmental paths

  20. Uranyl-organic assemblies with the macrocyclic ligand 1, 4, 8, 11-tetra-aza-cyclo-tetradecane-1, 4, 8, 11-tetraacetate (TETA)

    International Nuclear Information System (INIS)

    Thuery, Pierre

    2010-01-01

    Three uranyl ion complexes obtained from the reaction of uranyl nitrate hexahydrate and 1, 4, 8, 11-tetra-aza-cyclo-tetradecane-1, 4, 8, 11-tetraacetic acid (H 4 TETA) were characterized by their crystal structure. The centrosymmetric macrocycle, in the [3434] conformation with either carbon or nitrogen atoms as corners, is zwitterionic, with four carboxylate groups and two or four protonated nitrogen atoms. The complexes [(UO 2 ) 2 (H 2 TETA)(C 2 O 4 )(H 2 O) 2 ] (1) and [UO 2 (H 4 TETA)(H 2 O)].NO 3 .Cl (2) were synthesized under hydrothermal conditions and 1 includes additional oxalate ligands generated in situ. Both compounds are two-dimensional polymers in which the four-fold monodentate macrocyclic ligand unites either four uranyl oxalate dinuclear species (1) or isolated uranyl ions (2). Complex 3, [UO 2 (H 2 TETA)(H 2 O)].6H 2 O, was obtained at room temperature and, although it displays the same stoichiometry as 2, it differs from it by being a three-dimensional framework. Both 2 and 3 present channels containing either counter-ions or water molecules. As often observed, the water content of the low-temperature species, 3, is higher than that of the high-temperature one, 2. (author)

  1. 2-(3-Methylphenyl-1,2-benzoselenazol-3(2H-one

    Directory of Open Access Journals (Sweden)

    Liyun Wang

    2017-04-01

    Full Text Available In the title ebselen derivative, C14H11NOSe, the nine-membered benzisoselenazolyl ring system is approximately planar (r.m.s. deviation = 0.021 Å. The dihedral angle between its mean plane and that of the 3-methylphenyl ring is 5.37 (11°. The five-membered isoselenazolyl ring is severely strained at the Se atom: Se—N = 1.889 (2 Å, Se—Car = 1.882 (3 Å and N—Se—Car = 83.30 (10°. In the crystal, molecules are linked by C—H...O hydrogen bonds and short intermolecular Se...O contacts of 2.6917 (19 Å, forming chains along the c-axis direction. Neighbouring molecules are linked by offset π–π interactions [intercentroid distance = 3.535 (2 Å]. The chains are also linked by C—H...π interactions, forming a three-dimensional structure.

  2. Synthesis of the new boron hydride nido-undecaborane(15), B11H15, and the x-ray structure of its conjugate base tetradecahydroundecaborate(1-), [B11H14]-

    International Nuclear Information System (INIS)

    Getman, T.D.; Krause, J.A.; Shore, S.G.

    1988-01-01

    The preparation of nido-undecaborane, B 11 H 15 , from the protonation of K[B 11 H 14 ] and the subsequent deprotonation of B 11 H 15 by P(CH 3 ) 3 to give [P(CH 3 ) 3 H][B 11 H 14 ] is described. The structure of [P(CH 3 ) 3 H][B 11 H 14 ] has been determined from single-crystal x-ray data. The spectral data indicate that the boron framework of B 11 H 15 is similar to that of [B 11 H 14 ] - . 11 references, 1 figure

  3. (E-N′-[4-(Dimethylaminobenzylidene]-2-(4-methylphenoxyacetohydrazide

    Directory of Open Access Journals (Sweden)

    M. K. Usha

    2014-02-01

    Full Text Available In the title compound, C18H21N3O2, the dihedral angle between the benzene rings is 68.85 (11°. In the crystal, the molecules are linked by C—H...O and N—H...O hydrogen bonds, as well as weak C—H...π contacts, forming a three-dimensional supramolecular architecture.

  4. Synthesis and PET studies of [(11)C-cyano]letrozole (Femara), an aromatase inhibitor drug.

    Science.gov (United States)

    Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

    2009-02-01

    Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to

  5. The synthesis of the 2H, 3H, and 14C-isotopomers of 2'-deoxy-2',2'-difluorocytidine hydrochloride, an anti-tumor compound

    International Nuclear Information System (INIS)

    Wheeler, W.J.; Mabry, T.E.; Jones, C.D.

    1991-01-01

    The 2 H, 3 H, and 14 C-isotopomers of 2'-deoxy-2', 2'-difluorocytidine hydrochloride (gemcitabine hydrochloride) have been synthesized in two radiochemical steps from the reaction of bis-trimethylsilylcytosine-[2- 14 C] and 3,5-O-bis-benzoyl-1-O-methanesulfonyl-2-deoxy-2,2-difluororibose. A mixture of anomers of 3',5'-dibenzoyl-2'-deoxy-2',2'-difluorocytidine or its 14 C-isotopomer were obtained which were readily separated by crystallization from ethyl acetate. Deprotection using methanolic ammonia yielded the target compound. The 2 H and 3 H-isotopomers were prepared by deuterium (or tritium) gas hydrogenolysis of 5-iodo-2'-deoxy-2',2'-difluorocytidine. (author)

  6. Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.

    Science.gov (United States)

    Schwarzenböck, Sarah Marie; Schmeja, Philipp; Kurth, Jens; Souvatzoglou, Michael; Nawroth, Roman; Treiber, Uwe; Kundt, Guenther; Berndt, Sandra; Graham, Keith; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Ziegler, Sibylle I; Dinkelborg, Ludger; Wester, Hans-Jürgen; Krause, Bernd Joachim

    2016-06-01

    Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C

  7. Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients

    International Nuclear Information System (INIS)

    Forsberg, Anton; Andersson, Jan; Varnaes, Katarina; Halldin, Christer; Jureus, Anders; Swahn, Britt-Marie; Sandell, Johan; Julin, Per; Svensson, Samuel; Cselenyi, Zsolt; Schou, Magnus; Johnstroem, Peter; Farde, Lars; Eriksdotter, Maria; Freund-Levi, Yvonne; Jeppsson, Fredrik

    2013-01-01

    The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD). In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [ 11 C]AZD2995 and [ 11 C]AZD2184 in three healthy control subjects and seven AD patients. AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [ 3 H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [ 11 C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [ 11 C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus. Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [ 11 C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [ 11 C]AZD2995. However, the very low nonspecific binding of [ 11 C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy. (orig.)

  8. Synthesis of 9H-indeno [1, 2-b] pyrazine and 11H-indeno [1, 2-b] quinoxaline derivatives in one-step reaction from 2-bromo-4-chloro-1-indanone

    OpenAIRE

    Jasouri, S.; Khalafy, J.; Badali, M.; Prager, R.H.

    2011-01-01

    The reaction of 2-bromo-4-chloro-1-indanone with 2,3-diaminomaleonitrile, benzene-1,2-diamine and 4-methylbenzene-1,2-diamine in glacial acetic acid gave 8-chloro-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile, 1-chloro-11H-indeno[1,2-b]quinoxa-line and 1-chloro-7-methyl-11H-indeno[1,2-b]quinoxaline, respectively, in good yield.

  9. Different sensitivities to competitive inhibition of benzodiazepine receptor binding of {sup 11}C-iomazenil and {sup 11}C-flumazenil in rhesus monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Osamu; Hosoi, Rie; Kobayashi, Kaoru [Osaka Univ., Suita (Japan). Medical School; Itoh, Takashi; Gee, A.; Suzuki, Kazutoshi

    2001-04-01

    The in vivo binding kinetics of {sup 11}C-iomazenil were compared with those of {sup 11}C-flumazenil binding in rhesus monkey brain. The monkey was anesthetized with ketamine and intravenously injected with either {sup 11}C-iomazenil or {sup 11}C-flumazenil in combination with the coadministration of different doses of non-radioactive flumazenil (0, 5 and 20 {mu}g/kg). The regional distribution of {sup 11}C-iomazenil in the brain was similar to that of {sup 11}C-flumazenil, but the sensitivity of {sup 11}C-iomazenil binding to competitive inhibition by non-radioactive flumazenil was much less than that of {sup 11}C-flumazenil binding. A significant reduction in {sup 11}C-flumazenil binding in the cerebral cortex was observed with 20 {mu}g/kg of flumazenil, whereas a relatively smaller inhibition of {sup 11}C-iomazenil binding in the same region was observed with the same dose of flumazenil. These results suggest that {sup 11}C-flumazenil may be a superior radiotracer for estimating benzodiazepine receptor occupancy in the intact brain. (author)

  10. Synthesis and biodistribution of [C-11]procaterol, a beta(2)-adrenoceptor agonist for positron emission tomography

    NARCIS (Netherlands)

    Visser, TJ; van der Wouden, EA; van Waarde, A; Doze, P; Elsinga, PH; Vaalburg, W

    The potent, subtype-selective radioligand (+/-)-erythro-5-(1-hydroxy-2-[C-11]isopropyl-aminobutyl)-8-hydroxy-carbostyril ([C-11]procaterol) was synthesized and evaluated for visualization of pulmonary beta(2)-adrenoceptors with positron emission tomography (PET). Procaterol was labelled by reductive

  11. 2-(3-Hydroxybenzylaminoacetic acid

    Directory of Open Access Journals (Sweden)

    Li-Hua Zhi

    2011-07-01

    Full Text Available There are two independent 2-(3-hydroxybenzylaminoacetic acid molecules, C9H11NO3, in the asymmetric unit of the title compound. The dihedral angle between the benzene rings of the two independent molecules is 58.12 (4°. The crystal packing is stablized by intermolecular O—H...O and N—H...O hydrogen bonds.

  12. Crystal structure of (E-4,4,4-trifluoro-3-phenylbut-2-enoic acid

    Directory of Open Access Journals (Sweden)

    Alexey Barkov

    2015-12-01

    Full Text Available In the title compound, C10H7F3O2, the dihedral angle between the benzene ring and the ethylene plane is 76.34 (11°. In the crystal, O—H...O hydrogen bonds link the molecules into C(4 chains propagating in [010].

  13. Synthesis of 1-[11c]methylpiperidin-4-yl propionate ([11c]pmp) for in vivo measurements of acetylcholinesterase activity

    International Nuclear Information System (INIS)

    Snyder, Scott E.; Tluczek, Louis; Jewett, Douglas M.; Nguyen, Thinh B.; Kuhl, David E.; Kilbourn, Michael R.

    1998-01-01

    Synthesis of 1-[ 11 C]methylpiperidin-4-yl propionate ([ 11 C]PMP), an in vivo substrate for acetylcholinesterase, is reported. An improved preparation of 4-piperidinyl propionate (PHP), the immediate precursor for radiolabeling, was accomplished in three steps from 4-hydroxypiperidine by (a) protection of the amine as the benzyl carbamate, (b) acylation with propionyl chloride, and (c) deprotection of the carbamate by catalytic hydrogenation. The final product was obtained in an overall 82% yield. Reaction of the free base form of PHP with [ 11 C]methyl trifluoromethanesulfonate at room temperature in N,N-dimethylformamide, followed by high performance liquid chromatography (HPLC) purification, provided [ 11 C]PMP in 57% radiochemical yield, >99% radiochemical purity, and >1500 Ci/mmol at the end of synthesis. The total synthesis time from end-of-bombardment was 35 min. [ 11 C]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography

  14. Synthesis of carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolinium derivatives as new potential PET SKCa channel imaging agents.

    Science.gov (United States)

    Gao, Mingzhang; Wang, Min; Zheng, Qi-Huang

    2008-02-01

    Small conductance Ca2+-activated K+ (SKCa) channels play an important role in many functions such as neuronal communication and behavioral plasticity, secretion, and cell proliferation. SKCa channel modulation is associated with various brain, heart, and cancer diseases. N-methyl-laudanosine and its structurally related derivatives, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums, are reversible and selective SKCa channel blockers. Carbon-11 labeled N-methyl-laudanosine and its tetrahydroisoquinolinium derivatives may serve as new probes for positron emission tomography (PET) to image SKCa channels in the brain, heart, and cancer. The key intermediates, substituted isoquinolines (3a-c), were synthesized using a modification of the Pomeranz-Fritsch procedure. The precursors, substituted 1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolines (8a-c), and their corresponding reference standards, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums (9a-c), were synthesized from compounds 3a-c with 3,4-dimethoxybenzyl chloride (2) in multiple steps with moderate to excellent chemical yields. The precursor 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline (10) was commercially available, and the methylation of compound 10 with methyl iodide provided N-methyl-laudanosine (11). The target quaternary ammonium tracers, carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums ([11C]9a-c and [11C]11), were prepared by N-[11C]methylation of the tertiary amine precursors (8a-c and 10) with [11C]methyl triflate and isolated by a simplified solid-phase extraction (SPE) purification using a SiO2 or cation-exchange CM Sep-Pak cartridge in 40-65% radiochemical yields.

  15. Whole-body distribution and radiation dosimetry of the dopamine transporter radioligand [{sup 11}C]PE2I in healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Maria-Joao [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France)]. E-mail: maria-joao.ribeiro@cea.fr; Ricard, Marcel [Service de Physique, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France); Lievre, Marie-Angele [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France); Bourgeois, Sandrine [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France); Emond, Patrick [INSERM U316, Laboratoire de Biophysique medicale et pharmaceutique, UFR des Sciences Pharmaceutiques, 37200 Tours (France); Gervais, Philippe [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France); Dolle, Frederic [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France); Syrota, Andre [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France)

    2007-05-15

    Introduction: This study reports on the biodistribution and radiation dosimetry of a cocaine analog, the (E)-N-(3-iodoprop-2-enyl)-2{beta}-carbomethoxy-3{beta}-(4'-tolyl)nortropane (PE2I), labeled with carbon 11 ([{sup 11}C]PE2I). [{sup 11}C]PE2I is used in positron emission tomography (PET) for examination of the dopamine neuronal transporter (DAT). DAT radioligands are often used to evaluate the progression of Parkinson's disease or the efficiency of neuroprotective therapeutics, and, typically, these studies required several successive PET scans. Methods: In three healthy male volunteers, whole-body scans were performed up to 2 h following intravenous injection of 321{+-}6 MBq of [{sup 11}C]PE2I. For each subject, regions of interest were defined over all visible organs to generate time-activity curves and calculate the percentage of injected activity. Time-activity data were fitted to a monoexponential model, as an uptake phase followed by a mono-exponential washout, or bi-exponential model to obtain residence times. With the use of the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses. Results: Blood pressure and ECG findings remained unchanged after radioligand injection. The primary route of clearance was renal. Ten minutes after injection, high activities were observed in the kidneys, urinary-bladder, stomach, liver, salivary glands and brain. The urine bladder wall, stomach and liver received the highest absorbed doses. The average effective dose of [{sup 11}C]PE2I was estimated to be 6.4{+-}0.6 {mu}Sv/MBq. Conclusion: The amount of [{sup 11}C]PE2I required for adequate DAT PET imaging results in an acceptable effective dose equivalent permitting two or three repeated cerebral PET studies, with the injection of 222 MBq for each study.

  16. DETECTION OF H i IN EMISSION IN THE LY α EMITTING GALAXY HARO 11

    International Nuclear Information System (INIS)

    Pardy, Stephen A.; Cannon, John M.; Östlin, Göran; Hayes, Matthew; Bergvall, Nils

    2016-01-01

    We present the first robust detection of H i 21 cm emission in the blue compact galaxy Haro 11 using the 100 m Robert C. Byrd Green Bank Telescope (GBT). Haro 11 is a luminous blue compact galaxy with emission in both Ly α and the Lyman continuum. We detect (5.1 ± 0.7 × 10 8 ) M ⊙ of H i gas at an assumed distance of 88 Mpc, making this galaxy H i deficient compared to other local galaxies with similar optical properties. Given this small H i mass, Haro 11 has an elevated M H2 / M Hi ratio and a very low gas fraction compared to most local galaxies, and contains twice as much mass in ionized hydrogen as in neutral hydrogen. The H i emission has a linewidth of 71 km s − 1 and is offset 60 km s −1 redward of the optical line center. It is undergoing a starburst after a recent merger that has elevated the star formation rate, and will deplete the gas supply in <0.2 Gyr. Although this starburst has elevated the star formation rate (SFR) compared to galaxies with similar H i masses and line widths, Haro 11 matches a trend of lower gas fractions toward higher SFRs and is below the general trend of increasing H i mass with increasing luminosity. Taken together, our results paint Haro 11 as a standard low-mass galaxy that is undergoing an unusually efficient star formation episode.

  17. On Clebsch-Gordan expansion for 0(2h+1,1)

    International Nuclear Information System (INIS)

    Dobrev, V.; Petkova, V.; Petrova, S.; Mack, G.; Todorov, I.

    1974-01-01

    The direct-product expansion of two unitary representations of the supplementary series of 0(2h+1.1) is studied in detail. Invariant bi-linear forms are written down for arbitrary symmetric tensor representations and necessary and sufficient conditions are found for their positivity. Normalized Clebsh-Gordon kernels are evaluated explicitly and the Plancherel formula is verified. The results are applied elsewhere for the diagonalization of conformal covariant dynamical equations for the Euclidean Green functions. They are related to the derivation of covariant operator product expansions

  18. Radiosynthesis of (E)-N-(2-[{sup 11}C]methoxybenzyl)-3-phenyl-acrylamidine, a novel subnanomolar NR2B subtype-selective NMDA receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Thominiaux, Cyrille [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Bruin, Beatrice de [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Bramoulle, Yann [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Hinnen, Francoise [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Demphel, Stephane [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Valette, Heric [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Bottlaender, Michel [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Besret, Laurent [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Departement de Recherche Medicale, URA CEA/CNRS 2210, Service Hospitalier Frederic Joliot, CEA/DSV, 4 Place du General Leclerc, F-91401 Orsay (France); Kassiou, Michael [Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050 (Australia); Department of Pharmacology, University of Sydney, NSW 2006 (Australia); Dolle, Frederic [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France)]. E-mail: frederic.dolle@cea.fr

    2006-03-15

    Recently, a novel series of amidines has been described, exhibiting high NR2B-subtype selective N-methyl-D-aspartate (NMDA) antagonist activity with nanomolar or subnanomolar affinity. Within the styrylamidine subclass (E)-N-(2-methoxybenzyl)-3-phenyl-acrylamidine (1), displayed the highest affinity (Ki=0.7nM versus [{sup 3}H]ifenprodil) and was considered an appropriate candidate for isotopic labelling with carbon-11 (T{sub 1/2}: 20.38min) at its methoxy group for imaging of NMDA receptors with PET. Derivative 1 has been labelled from the corresponding nor-analogue using [{sup 11}C]methyl triflate and the following experimental conditions : (1) trapping at -10{sup o}C of [{sup 11}C]methyl triflate in 300{mu}L of acetone containing 0.6-0.8mg of precursor 5 (2.4-3.2{mu}mol) and 5{mu}L of a 3M solution of NaOH in water (about 5eq.); (2) concentration to dryness of the reaction mixture (at 110{sup o}C, using a helium stream for 1-2min); (3) taking up the residue with 0.5mL of the HPLC mobile phase and (4) purification using semi-preparative HPLC (SymmetryPrep{sup (}R) C-18, Waters, 300x7.8mm). Typically, starting from a 1.5 Ci (55.5GBq) [{sup 11}C]CO{sub 2} production batch, 120-240m Ci (4.44-8.88GBq) of [{sup 11}C]-1 (20-40% decay-corrected radiochemical yield, n=5) was obtained within a total synthesis time of 25-30min. Specific radioactivities ranged from 0.8 to 1.2Ci/{mu}mol (29.6-44.4GBq/{mu}mol) at the end of radiosynthesis. No attempts were made to further optimise these reactions, as sufficient material was obtained to allow for preliminary pharmacological characterisation.

  19. 2-(5-Fluoro-3-methylsulfanyl-1-benzofuran-2-ylacetic acid

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2009-08-01

    Full Text Available The title compound, C11H9FO3S, was prepared by alkaline hydrolysis of ethyl 2-(5-fluoro-3-methylsulfanyl-1-benzofuran-2-ylacetate. In the crystal structure, the carboxyl groups are involved in intermolecular O—H...O hydrogen bonds, which link the molecules into centrosymmetric dimers. These dimers are further packed into stacks along the b axis by intermolecular C—H...O and C—H...F interactions.

  20. 4-Aminobenzoic acid–1,2-bis(4-pyridylethane (2/1

    Directory of Open Access Journals (Sweden)

    Fwu Ming Shen

    2010-07-01

    Full Text Available In the title compound, C12H12N2·2C7H7NO2, the 4-aminobenzoic acid molecules are linked by O—H...N hydrogen bonds to 1,2-bis(4-pyridylethane, forming linear hydrogen bonded chains parallel to [2overline{1}1]. The structure exhibits a hydrogen-bonding network involving COOH...N(pyridyl and amine and carboxylic N—H... O interactions. In addition, π–π stacking interactions [centroid–centroid distance = 3.8622 (14 Å] are also present.

  1. 1,1′-Bis(3-methyl-3-phenylcyclobutyl-2,2′-(azanediyldiethanol

    Directory of Open Access Journals (Sweden)

    Fatih Şen

    2012-04-01

    Full Text Available The title molecule, C26H35NO2, contains two cyclobutane rings that adopt butterfly conformations and are linked by a –CH(OHCH2NHCH2CH(OH– bridge. In the crystal, N—H...O, O—H...N and O—H...O hydrogen bonds together with C–H...π interactions link the molecules.

  2. mer-Bis[3,5-difluoro-2-(2-pyridylphenyl-κ2C1,N]{5-(2-pyridyl-κN-3-[3-(4-vinylbenzyloxyphenyl]-1,2,4-triazol-1-ido}iridium(III methanol solvate

    Directory of Open Access Journals (Sweden)

    Peter G. Jones

    2010-01-01

    Full Text Available In the title compound, [Ir(C11H6F2N2(C22H17N4O]·CH3OH, the coordination at iridium is essentially octahedral, but with distortions associated with the bite angles of the ligands [76.25 (9–80.71 (12°] and the differing trans influences of C and N ligands [Ir—N = 2.04 Å (average trans to N but 2.14 Å trans to C]. All three bidentate ligands have coordinating ring systems that are almost coplanar [interplanar angles = 1.7 (1–3.8 (2°]. The vinylbenzyl group is disordered over two positions with occupations of 0.653 (4 and 0.347 (4. The methanol solvent molecule is involved in a classical O—H...N hydrogen bond to a triazole N atom.

  3. Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library.

    Science.gov (United States)

    Welford, Amanda J; Caldwell, John J; Liu, Manjuan; Richards, Meirion; Brown, Nathan; Lomas, Cara; Tizzard, Graham J; Pitak, Mateusz B; Coles, Simon J; Eccles, Suzanne A; Raynaud, Florence I; Collins, Ian

    2016-04-11

    The 2,11-cembranoid family of natural products has been used as inspiration for the synthesis of a structurally simplified, functionally diverse library of octahydroisobenzofuran-based compounds designed to augment a typical medicinal chemistry library screen. Ring-closing metathesis, lactonisation and SmI2 -mediated methods were exemplified and applied to the installation of a third ring to mimic the nine-membered ring of the 2,11-cembranoids. The library was assessed for aqueous solubility and permeability, with a chemical-space analysis performed for comparison to the family of cembranoid natural products and a sample set of a screening library. Preliminary investigations in cancer cells showed that the simpler scaffolds could recapitulate the reported anti-migratory activity of the natural products. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  4. The threshold photoelectron spectrum of the geminal chloro-fluoro-ethene (1,1-C2H2FCl) isomer. Experiment and theory

    International Nuclear Information System (INIS)

    Locht, R; Leyh, B; Dehareng, D

    2014-01-01

    The threshold photoelectron spectrum (TPES) of 1,1-C 2 H 2 FCl has been measured for the first time using synchrotron radiation. It has been compared to the HeI PES obtained earlier (Tornow et al 1990 Chem. Phys. 146 115). Eight photoelectron bands have been observed at 10.22, 12.45, 13.28, 14.29, 14.99, 17.12, 17.67 and at 20.23 eV successively. Only the first three bands exhibit a rich and extensive vibrational structure. Their adiabatic ionization energies are measured and a detailed vibrational analysis is presented. The assignments of the electronic bands and of the vibrational wavenumbers were made by using ab initio quantum chemical calculations. These allowed us to provide the MO description of the eight electronic states in terms of ionization and double excitation. The good correlation between predicted vibrational wavenumbers and the experimental values provides a strong basis for the assignment of all the vibrational structures. (paper)

  5. Cholinergic PET imaging in infections and inflammation using 11C-donepezil and 18F-FEOBV

    DEFF Research Database (Denmark)

    Jørgensen, Nis Pedersen; Alstrup, Aage Kristian Olsen; Mortensen, Frank Viborg

    2017-01-01

    with Staphylococcus aureus, and PET scanned at 24, 72, 120, and 144 h post-inoculation. Four pigs with post-operative abscesses were also imaged. Finally, we present initial data from human patients with infections, inflammation, and renal and lung cancer. Results In mice, the FDG uptake in abscesses peaked at 24 h...... and remained stable. The 11C-donepezil and 18F-FEOBV uptake displayed progressive increase, and at 120–144 h was nearly at the FDG level. Moderate 11C-donepezil and slightly lower 18F-FEOBV uptake were seen in pig abscesses. PCR analyses suggested that the 11C-donepezil signal in inflammatory cells is derived...... from both acetylcholinesterase and sigma-1 receptors. In humans, very high 11C-donepezil uptake was seen in a lobar pneumonia and in peri-tumoral inflammation surrounding a non-small cell lung carcinoma, markedly superseding the 18F-FDG uptake in the inflammation. In a renal clear cell carcinoma no 11C...

  6. Development and automation of a novel NET-PET tracer: [11C]Me@APPI.

    Science.gov (United States)

    Mark, Christina; Bornatowicz, Birgit; Mitterhauser, Markus; Hendl, Matthias; Nics, Lukas; Haeusler, Daniela; Lanzenberger, Rupert; Berger, Michael L; Spreitzer, Helmut; Wadsak, Wolfgang

    2013-02-01

    The norepinephrine transporter (NET) is an important target for research in neurology and psychology and is involved in the pathophysiology of many neurodegenerative diseases such as Alzheimer's disease and attention deficient hyperactivity disorder. For visualization of NET abundance and deregulation, a novel PET tracer--[(11)C]Me@APPI--has been developed. For precursor synthesis, a 4-step synthesis starting from N-phenyl-o-phenylenediamine was set up. Radiosynthesis was established and optimized using standard methods and subsequently automated in a GE TRACERlabFx C Pro synthesizer. Preclinical testing was performed comprising affinity and selectivity testing on human membranes as well as stability and blood-brain-barrier-penetration using in-vitro models. Precursor molecule (APPI:0) and reference compound (Me@APPI) were synthesized with 26.5% and 21.4% overall yield, respectively. So far, 1.25±0.72 GBq [(11)C]Me@APPI with 54.35±7.80 GBq/μmol specific activity were produced (n=11). Affinity of reference compounds was determined as 8.08±1.75 nM for Me@APPI and 19.31±2.91 nM for APPI:0, respectively (n≥9). IAM-chromatography experiments (n=3) revealed a P(m) value of 1.51±0.34 for Me@APPI. Stability testing using human liver microsomes revealed that 99.5% of the tracer was found to be still intact after 60 minutes (n=4). Present data indicate that [(11)C]Me@APPI has promising properties to become a clinically useful NET-PET-tracer. Further in-vitro and in-vivo evaluations are currently under way. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Development and automation of a novel NET-PET tracer: [11C]Me@APPI

    International Nuclear Information System (INIS)

    Mark, Christina; Bornatowicz, Birgit; Mitterhauser, Markus; Hendl, Matthias; Nics, Lukas; Haeusler, Daniela; Lanzenberger, Rupert; Berger, Michael L.; Spreitzer, Helmut; Wadsak, Wolfgang

    2013-01-01

    Introduction: The norepinephrine transporter (NET) is an important target for research in neurology and psychology and is involved in the pathophysiology of many neurodegenerative diseases such as Alzheimer's disease and attention deficient hyperactivity disorder. For visualization of NET abundance and deregulation, a novel PET tracer – [ 11 C]Me@APPI – has been developed. Methods: For precursor synthesis, a 4-step synthesis starting from N-phenyl-o-phenylenediamine was set up. Radiosynthesis was established and optimized using standard methods and subsequently automated in a GE TRACERlabFx C Pro synthesizer. Preclinical testing was performed comprising affinity and selectivity testing on human membranes as well as stability and blood–brain-barrier-penetration using in-vitro models. Results: Precursor molecule (APPI:0) and reference compound (Me@APPI) were synthesized with 26.5% and 21.4% overall yield, respectively. So far, 1.25 ± 0.72 GBq [ 11 C]Me@APPI with 54.35 ± 7.80 GBq/μmol specific activity were produced (n = 11). Affinity of reference compounds was determined as 8.08 ± 1.75 nM for Me@APPI and 19.31 ± 2.91 nM for APPI:0, respectively (n ≥ 9). IAM-chromatography experiments (n = 3) revealed a P m value of 1.51 ± 0.34 for Me@APPI. Stability testing using human liver microsomes revealed that 99.5% of the tracer was found to be still intact after 60 minutes (n = 4). Conclusion: Present data indicate that [ 11 C]Me@APPI has promising properties to become a clinically useful NET-PET-tracer. Further in-vitro and in-vivo evaluations are currently under way

  8. Phase relation of LaFe11· 6Si1· 4 compounds annealed at different ...

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 35; Issue 2. Phase relation of LaFe11.6Si1.4 compounds annealed at different high-temperature and the magnetic property of LaFe11.6−CoSi1.4 compounds. Xiang Chen Yungui Chen Yongbai Tang. Volume 35 Issue 2 April 2012 pp 175-182 ...

  9. (/sup 11/C )-DMO for evaluation of regional tissue pH in patients with hemispheric infarction using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Castaing, M; Syrota, A; Rougemont, D; Berridge, M; Chretien, L; Baron, J C; Bousser, M G

    1983-06-01

    Changes in brain intracellular pH resulting from cerebral infarction were evaluated using the /sup 11/C-DMO (dimethyloxazolidine-dione) method, in 9 patients. A /sup 15/O/sub 2/-C/sup 15/O/sub 2/ study was performed the day following the DMO examination in order to obtain the values of cerebral blood flow, oxygen extraction and oxygen metabolic rate in the same regions-of-interest. The results emphasized the relationship between tissue alkalosis and luxury perfusion during recent infarction.

  10. Evaluation of the kappa-opioid receptor-selective tracer [{sup 11}C]GR103545 in awake rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Schoultz, Bent W. [University of Oslo, Department of Chemistry, Oslo (Norway); Hjornevik, Trine; Willoch, Frode [University of Oslo, Centre for Molecular Biology and Neuroscience and Institute of Basic Medical Sciences, Oslo (Norway); Akershus University Hospital, Department of Nuclear Medicine, Loerenskog (Norway); Marton, Janos [ABX Advanced Biochemical Compounds GmbH, Radeberg (Germany); Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro [Medical and Pharmacological Research Center Foundation, Basic Research Department, Hakui City, Ishikawa (Japan); Aarstad, Erik [University College of London, Institute of Nuclear Medicine, London (United Kingdom); Drzezga, Alexander [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Matsunari, Ichiro [Medical and Pharmacological Research Center Foundation, Clinical Research Department, Hakui City, Ishikawa (Japan); Henriksen, Gjermund [University of Oslo, Department of Chemistry, Oslo (Norway); Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

    2010-06-15

    The recent development in radiosynthesis of the {sup 11}C-carbamate function increases the potential of [{sup 11}C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor ({kappa}-OR) with PET. In the present study, [{sup 11}C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [{sup 11}C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [{sup 11}C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for {kappa}-OR (K{sub i} = 0.02 {+-}0.01 nM) with excellent selectivity over {mu}-OR (6 x 10{sup 2}-fold) and {delta}-OR (2 x 10{sup 4}-fold). PET imaging revealed a volume of distribution (V{sub T}) pattern consistent with the known distribution of {kappa}-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [{sup 11}C]GR103545 is selective for {kappa}-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

  11. (S)- and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. Preparation, metabolite studies and in vivo distribution in the human brain using PET

    International Nuclear Information System (INIS)

    Halldin, C.; Swahn, C.-G.; Nybaeck, H.; Naagren, K.; Laangstroem, B.

    1992-01-01

    In order to investigate [ 11 C]nicotine binding and metabolism in the living human brain by PET, routine protocols were developed for the preparation and purification of (S)-and (R)-[ 11 C]nicotine and the metabolite (R/S)-[ 11 C]cotinine. (S)- and (R)-[ 11 C]nicotine were prepared by N-methylation with [ 11 C]methyl iodide of the appropriate secondary amine, which was liberated in situ by 2,2,6,6,-tetramethylpiperidine (TMP) from its corresponding biscamsylate-salt. (R/S)-[ 11 C]Cotinine was prepared by N-methylation of the amide precursor using tetrabutylammonium hydroxide as a phase transfer catalyst. Straight-phase semipreparative HPLC was in all purifications found to be superior to reversed-phase since the contamination by the norcompounds was eliminated. Reaction in acetonitrile for both (S)- and (R)-[ 11 C]nicotine and (R/S)-[ 11 C]cotinine with subsequent straight-phase HPLC purification resulted in 35-45% radiochemical yield with a total synthesis time of 30-35 min, a specific radioactivity of 1000-1500 Ci/mmol (37-55 GBq/μmol, EOS) and a radiochemical purity >99%. The uptake and distribution of these tracers in the human brain was studied in healthy volunteers by PET. The metabolite (R/S)-[ 11 C]cotinine did not cross the blood-brain barrier to any significant degree. (author)

  12. Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients

    International Nuclear Information System (INIS)

    Abrahim, Aiman; Langer, Oliver; Luurtsema, Gert; Lubberink, Mark; Lammertsma, Adriaan A.; Bauer, Martin; Joukhadar, Christian; Mueller, Markus; Karch, Rudolf; Pataraia, Ekaterina; Baumgartner, Christoph; Kletter, Kurt

    2008-01-01

    (R)-[ 11 C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[ 11 C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[ 11 C]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers. Arterial blood samples were collected from eight patients undergoing (R)-[ 11 C]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[ 11 C]verapamil by using an assay that measures polar N-demethylation metabolites by solid-phase extraction and lipophilic N-dealkylation metabolites by HPLC. Peripheral metabolism of (R)-[ 11 C]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R)-[ 11 C]verapamil fraction in plasma: 29.4 ± 3.9 min for patients versus 40.8 ± 5.0 min for healthy volunteers; p 11 C]verapamil plasma concentrations (AUC of (R)-[ 11 C]verapamil concentration, normalised to injected dose per body weight: 25.5 ± 2.1 min for patients and 30.5 ± 5.9 min for healthy volunteers; p = 0.038). Faster metabolism appeared to be mainly due to increased N-demethylation as the polar [ 11 C]metabolite fraction was up to two-fold greater in patients. Faster metabolism of (R)-[ 11 C]verapamil in epilepsy patients may be caused by hepatic cytochrome P450 enzyme induction by antiepileptic drugs. Based on these data caution is warranted when using an averaged arterial input function derived from healthy volunteers for the analysis of patient data. Moreover, our data illustrate how antiepileptic drugs may decrease serum levels of concomitant medication, which may eventually lead to a loss of therapeutic efficacy. (orig.)

  13. 2,5,11,14-Tetraoxa-8-azadispiro[13.4.0]nonadeca-15,17,19-triene

    Directory of Open Access Journals (Sweden)

    Quanying Gan

    2010-05-01

    Full Text Available The title compound, C14H21NO4, has been synthesized from o-dihydroxybenzene by a three-step reaction. There are two chemically equal but crystallographically independent molecules in the asymmetric unit. The crystal packing is governed by C—H...O hydrogen bonds and C—H...π interactions, forming an infinite network.

  14. (Pyridine-2-aldoximato-κ2N,N′bis[2-(pyridin-2-ylphenyl-κ2C1,N]iridium(III

    Directory of Open Access Journals (Sweden)

    Bimal Chandra Singh

    2013-03-01

    Full Text Available In the title complex, [Ir(C11H8N2(C6H5N2O], the octahedrally coordinated IrIII atom is bonded to two 2-(pyridin-2-ylphenyl ligands, through two phenyl C and two pydidine N atoms, and to one pyridine-2-aldoxime ligand through a pyridine N and an oxime N atom. The oxime O atom of the aldoxime unit forms intermolecular C—H...O hydrogen bonds, which result in a two-dimensional hydrogen-bonded polymeric network parallel to (100. C—H...π interactions are also observed.

  15. 4-Hydroxy-3-methoxybenzaldehyde–nicotinamide (1/1

    Directory of Open Access Journals (Sweden)

    Fiona N.-F. How

    2011-12-01

    Full Text Available In the title compound, C6H6N2C8H8O3, an equimolar co-crystal of nicotinamide and vanillin, the aromatic ring and the amide fragment of the nicotinamide molecule make a dihedral angle of 32.6 (2°. The vanillin molecule is almost planar, with an r.m.s. deviation for all non-H atoms of 0.0094 Å. The vaniline and nicotinamide aromatic rings are nearly coplanar, the dihedral angle between them being 3.20 (9°. In the crystal, the two components are linked through N—H...O and O—H...N hydrogen bonds into chains along the a axis. The chains are connected via C—H...O interactions, forming a three-dimensional polymeric structure.

  16. QUANTIFICATION OF AN C-11 LABELED BETA-ADRENOCEPTOR LIGAND, S-(-)CGP-12177, IN PLASMA OF HUMANS AND RATS

    NARCIS (Netherlands)

    VANWAARDE, A; ANTHONIO, RL; ELSINGA, PH; POSTHUMUS, H; WEEMAES, AMA; BLANKSMA, PK; PAANS, AMJ; VAALBURG, W; Visser, Ton J.; Visser, Gerben

    1995-01-01

    beta-Adrenoceptors in human lungs and heart can be imaged with the radioligand 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1 ,3-dihydro-2H-benzimidazol-2-C-11-one (CGP 12177, [C-11]I). For quantification of receptor density with compartment models by adjustment of rate constants, an 'input

  17. 5-Bromo-2-[5-(4-nitrophenyl-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]pyrimidine

    Directory of Open Access Journals (Sweden)

    B. Kalluraya

    2009-12-01

    Full Text Available In the title pyrazoline compound, C19H14BrN5O2, the essentially planar pyrazoline and pyrimidine rings [maximum deviations = 0.013 (1 and 0.009 (1 Å, respectively] are inclined slightly to one another, making a dihedral angle of 10.81 (10°. The nitrobenzene unit is almost perpendicular to the attached pyrazoline ring, as indicated by the dihedral angle of 84.61 (8°. In the crystal structure, intermolecular C—H...N contacts link the molecules into dimers in an antiparallel manner. These dimers are further linked into one-dimensional chains along the b axis via C—H...O contacts. The crystal structure is consolidated by three different intermolecular π–π interactions [range of centroid–centroid distances = 3.5160 (11–3.6912 (11 Å].

  18. 1-Benzyl-3′-[(1H-indol-3-ylcarbonyl]-1′-methyl-2-oxo-4′-(pyridin-3-ylspiro[indoline-3,2′-pyrrolidine]-3′-carbonitrile

    Directory of Open Access Journals (Sweden)

    P. Seethalakshmi

    2016-11-01

    Full Text Available In the title compound, C34H27N5O2, the central pyrrolidine ring adopts an envelope conformation, with the N atom as the flap. The mean planes of the two indoline ring systems are inclined to the mean plane of the central pyrrolidine ring by 86.26 (9 and 69.30 (9°, respectively. The dihedral angle between the benzene and pyridine rings is 75.09 (11°. In the crystal, molecules are linked by N—H...N and C—H...N hydrogen bonds, forming sheets parallel to the ab plane.

  19. Synthesis of (+-)-(1,1'- sup 15 N sub 2 , 2'- sup 13 C)-trans-3'-methylnicotine

    Energy Technology Data Exchange (ETDEWEB)

    Sirimanne, S.R.; Maggio, V.L.; Patterson, D.G. Jr. (Department of Health and Human Services, Atlanta, GA (United States))

    1992-03-01

    The synthesis of ({+-})- (1,1'-{sup 15}N{sub 2}, 2'-{sup 13}C)-trans-3'-methylnicotine is reported. {sup 15}N-3-Bromopyridine obtained from bromination of pyridine was formylated with nBuLi/(carbonyl-{sup 13}C)-methyl formate. The resulting {sup 15}n-Pyridine-3-({sup 13}C-carbonyl)-carboxaldehyde was reacted with {sup 15}N-methylamine and then the resulting Schiff's base was condensed with succinic anhydride to give ({+-})- (1,1'-{sup 15}N{sub 2}, 5'-{sup 13}C)-trans-4'-carboxycotinine. Reduction with lithium aluminum hydride and mesylation followed by reduction with Zn/NaI gave ({+-})-(1,1'-{sup 15}N{sub 2}, 2'-{sup 13}C)-trans-3'-methylnicotine. (Author).

  20. Heterocyclic Analogues of Xanthone and Xanthione. 1H-Pyrano[2,3-c:6,5-c]dipyrazol-4(7H-ones and Thiones: Synthesis and NMR Data

    Directory of Open Access Journals (Sweden)

    Wolfgang Holzer

    2010-09-01

    Full Text Available The synthesis of the title compounds is described. Reaction of 1-substituted 2-pyrazolin-5-ones with 5-chloro-1-phenyl-1H-pyrazole-4-carbonyl chloride or 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbonyl chloride, respectively, using calcium hydroxide in refluxing 1,4-dioxane gave the corresponding 4-heteroaroylpyrazol-5-ols, which were cyclized into 1H-pyrano[2,3-c:6,5-c]dipyrazol-4(7H-ones by treatment with K2CO3/DMF. The latter were converted into the corresponding thiones upon reaction with Lawesson’s reagent. Detailed NMR spectroscopic investigations (1H, 13C, 15N of the ring systems and their precursors are presented.

  1. Synthesis and crystal structure of trans-[Ni(pyzdcH)M 2 (H 2 O) 2 ...

    African Journals Online (AJOL)

    The determined structure of the title compound C24H20Ni2N8O20 consists of the mononuclear trans-[Ni(pyzdc)2(H2O)2], (pyzdc = pyrazine-2,3- dicarboxylate). The Ni(II) atom is hexa-coordinated by two (pyzdcH)- groups and two water molecules. The coordinated water molecules are in trans-diaxial positions and the ...

  2. Quality control of 11C-carfentanil

    International Nuclear Information System (INIS)

    Zhang Xiaojun; Zhang Jinming; Tian Jiahe; Xiang Xiaohui

    2013-01-01

    To study the quality control of 11 C-Carfentanil injection, physical, chemical and biological identification were used. The chemical and radiochemical purity of 11 C-Carfentanil Injection were detected by HPLC and Flower Count system; measured the quantity of product by LC-MS, specific activity was calculated later; The PTS was used to detect endotoxin, and other quality control methods were put up to guarantee the security of its clinical application. The produce appeared colorless and transparent, the radiochemical purity was more than 98%, content of the endotoxin was less than 5 EU/mL. The result showed that 11 C-Carfentanil injection had fulfilled pharmaceutical quality control request and could be applied safely to animal experiment and clinical diagnosis. (authors)

  3. Cytochrome P450-2C11 mRNA is not expressed in endothelial cells dissected from rat renal arterioles.

    Science.gov (United States)

    Heil, Sandra G; De Vriese, An S; Kluijtmans, Leo A J; Dijkman, Henry; van Strien, Denise; Akkers, Robert; Blom, Henk J

    2005-01-01

    Cytochrome P450 (CYP) isoenzymes (CYP2C and CYP2J) are involved in the production of epoxyeicosatrienoic acids, which are postulated as endothelium-derived hyperpolarizing factors (EDHFs). We hypothesized that if CYP2C11 is involved in the EDHF-mediated responses, its mRNA should be expressed in endothelial cells. We, therefore, examined the mRNA expression of CYP2C11 in endothelial cells of renal arterioles. Laser microdissection was applied to isolate endothelial cells from the renal arterioles of 4 male and 4 female Wistar rats. As a positive control of CYP2C11 expression, hepatocytes were also dissected from these rats. RNA was isolated and real-time quantitative polymerase chain reaction (Q-PCR) analysis was applied. Q-PCR analysis showed that CYP2C11 mRNA was not expressed in laser microdissected endothelial cells of renal arterioles of male and female rats. CYP2C11 mRNA expression was highly abundant in hepatocytes dissected from male livers, but in female livers hardly any CYP2C11 mRNA was detected. We have shown that endothelial cells can be dissected from small renal arterioles by laser microdissection to study the mRNA expression of specific genes by Q-PCR. Using this novel tool, we demonstrated that the CYP2C11 mRNA was not expressed in the endothelial cells of renal arterioles. Therefore, we speculate that CYP2C11 does not contribute to the EDHF-mediated responses in renal arterioles. Copyright (c) 2005 S. Karger AG, Basel.

  4. Design, Synthesis, Fluorescence Properties and Antibacterial Activities of New 8-Chloro-3-Alkyl-3H-Pyrazolo[4,3-a]acridine-11-Carbonitriles

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, Zeynab; Pordel, Mehdi; Davoodnia, Abolghasem [Islamic Azad Univ., Mashhad (Iran, Islamic Republic of)

    2014-02-15

    The treatment of alkylated nitro derivatives of indazole with 2-(4-chlorophenyl)acetonitrile under basic conditions gave the new 8-chloro-3-alkyl-3H-pyrazolo[4,3-a]acridine-11-carbonitriles via the nucleophilic substitution of hydrogen which proceeds at room temperature with concomitant cyclisation in fairly good yields. The structures of all newly synthesized compounds were confirmed by IR, {sup 1}H NMR, {sup 13}C NMR and mass spectral data. Fluorescence experimental results of all newly synthesized compounds revealed remarkable photoluminescence properties and strong green fluorescence properties. Also, the new compounds exhibited potent antibacterial activity and their antibacterial activity (MIC) against Gram positive (Staphylococcuse aureus methicillin resistant S. aureus and Bacillus subtilis) and negative bacterial (Pseudomonas aeruginosa and Escherichia coli) species were determined.

  5. Chlorido{4-ethyl-1-[1-(pyrazin-2-ylethylidene]thiosemicabazidato-κS}bis(triphenylphosphane-κPsilver(I

    Directory of Open Access Journals (Sweden)

    Md. Alamgir Hossain

    2013-03-01

    Full Text Available The title compound, [Ag(C9H13N5SCl(C18H15P2], crystallizes with four independent molecules in the asymmetric unit, in each of which the Ag atom is in a distorted tetrahedral coordination, defined by the chloride ligand, the S atom of the neutral ligand and two P atoms derived from the triphenyl phosphine ligands. The thiosemicarbazone acts as a monodentate ligand through its thione S atom. An intramolecular N—H...Cl hydrogen bond occurs in two of the independent molecules. In the crystal, the molecules are assembled through N—H...Cl hydrogen bonds, forming chains along [101].

  6. Catalytic conversion of 11C-labeled methanol over Cs-ZSM-5 zeolite

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Kovacs, Z.; Kumar, N.; Salmi, T.; Murzin, D.Yu.

    2004-01-01

    Reaction mechanism of the conversion of 11 C labeled methanol over basic Cs-ZSM-5 zeolite catalyst was investigated and the reaction products obtained were compared with that of H-ZSM-5 acidic catalyst. The catalytic experiments were carried out by passing 11 C-labeled methanol with He as a carrier gas over Cs-ZSM-5 packed in a micro reactor. After adsorption of the radio methanol, the catalyst was heated up to 330 deg C. The products of the catalytic conversion of the 11 C-labeled methanol were analyzed by radio-gas chromatography (gas chromatograph with thermal conductivity detector on-line coupled with a radioactivity detector). (N.T.)

  7. Diaqua[(1R,2S,4R,8R,9S,11R-2,9-dimethyl-1,4,8,11-tetraazacyclotetradecane]nickel(II dichloride dihydrate

    Directory of Open Access Journals (Sweden)

    James Alan Townsend

    2012-08-01

    Full Text Available The crystal structure of the title complex, [Ni(C12H28N4(H2O2]Cl2·2H2O, displays O—H...Cl and O—H...O hydrogen bonding. The tetraazacyclotetradecane ligand interacts with the NiII atom in the cis V configuration and the final two ligand binding sites are occupied by water.

  8. 5-Fluoro-6′H,7′H,8′H-spiro[indoline-3,7′-pyrano[3,2-c:5,6-c′]di-1-benzopyran]-2,6′,8′-trione

    Directory of Open Access Journals (Sweden)

    J. Suresh

    2012-03-01

    Full Text Available In the title compound, C26H12FNO6, the central pyran ring and both benzopyran systems are nonplanar, having total puckering amplitudes of 0.139 (2, 0.050 (1 and 0.112 (2 Å, respectively. The central pyran ring adopts a boat conformation. The crystal structure is stabilized by C—H...O, N—H...O, N—H...F and C—H...π interactions.

  9. Syntheses and Thermal Behaviors of Rb(FOX-7)·H2O and Cs(FOX-7)·H2O

    International Nuclear Information System (INIS)

    Luo, Jinan; Xu, Kangzhen; Wang, Min; Ren, Xiaolei; Chen, Yongshun; Song, Jirong; Zhao, Fengqi

    2010-01-01

    Two new energetic organic alkali metal salts, 1,1-diamino-2,2-dinitroethylene rubidium salt [Rb(FOX-7)·H 2 O] and 1,1- diamino-2,2-dinitroethylene cesium salt [Cs(FOX-7)·H 2 O], were synthesized by reacting of 1,1-diamino-2,2-dinitroethylene (FOX-7) and rubidium chloride or cesium chloride in alkali methanol aqueous solution, respectively. The thermal behaviors of Rb(FOX-7)·H 2 O and Cs(FOX-7)·H 2 O were studied with DSC and TG methods. The critical temperatures of thermal explosion of the two compounds are 216.22 and 223.73 .deg. C, respectively. Specific heat capacities of the two compounds were determined with a micro-DSC method, and the molar heat capacities are 217.46 and 199.47 J mol -1 K -1 at 298.15 K, respectively. The adiabatic times-to-explosion were also calculated to be a certain value of 5.81 - 6.36 s for Rb(FOX-7)·H 2 O, and 9.92 - 10.54 s for Cs(FOX-7)·H 2 O. After FOX-7 becoming alkali metal salts, thermal decomposition temperatures of the compounds heighten with the rise of element period, but thermal decomposition processes become intense

  10. μ-Carbonato-κ4 O,O′:O′,O′′-bis­{[2′-(di-tert-butyl­phosphan­yl)biphenyl-2-yl-κ2 P,C 1]palladium(II)} dichloro­methane monosolvate

    Science.gov (United States)

    Muller, Alfred; Holzapfel, Cedric W.

    2012-01-01

    The title compound, [(μ2-CO3){Pd(P(t-C4H9)2(C12H8)}2]·CH2Cl2, the first CO3-bridged palladium dimer complex reported to date, was obtained while preparing the Pd0 complex with (2-biphen­yl)P(tBu)2. In the crystal, each palladium dimer is accompanied by a dichloro­methane solvent mol­ecule. Coordination of the carbonate and chelated phosphane ligands gives distorted square-planar environments at the Pd atoms. Important geometrical parameters include Pd—P(av.) = 2.2135 (4) Å, Pd—C(av.) = 1.9648 (16) Å and P—Pd—C = 84.05 (5) and 87.98 (5)°, and O—Pd—O′ = 60.56 (4) and 61.13 (4)°. Bonding with the carbonate O atoms shows values of 2.1616 (11) and 2.1452 (11) Å for the Pd—O—Pd bridge, whereas other Pd—O distances are slightly longer at 2.2136 (11) and 2.1946 (11) Å. One of the tert-butyl groups is disordered over two set of sites with an occupancy ratio of 0.723 (6):0.277 (6). Weak C—H⋯O interactions are observed propagating the molecules along the [100] direction. PMID:23468771

  11. The synthesis of 5-(1- sup 11 C)ethyl barbiturates from labelled malonic esters

    Energy Technology Data Exchange (ETDEWEB)

    Gee, A.; Laangstroem, B. (Uppsala Univ. (Sweden). Dept. of Organic Chemistry)

    1991-01-01

    The synthesis of ({sup 11}C)phenobarbital, ({sup 11}C)pentobarbital and({sup 11}C)amobarbital labelled in the 5-(1-{sup 11}C)ethyl position is reported. The malonic esters R- CH(CO{sub 2}Et){sub 2} R phenyl-, 1-methylbutyl-, and 3- methylbutyl- were alkylated with (1-{sup 11}C)ethyl iodide prepared from ({sup 11}C)carbon dioxide. Ring closure of the 2-(1-{sup 11}C)ethyl-labelled malonic esters with urea afforded 5-(1-{sup 11}C)ethyl-phenobarbital,-phenobarbital, -pentobarbital and -amobarbital synthesis times of 42-47 min, counted from ({sup 11}C) carbon dioxide. In typical syntheses starting with 3 GBq pentobarbitol and (81 mCi) ({sup 11}C)carbon dioxide, 150-215 MBq (4-6 mCi) were produced in 25-30% decay corrected -amobarbital radiochemical yields with radiochemical purities greater than 98%. (author).

  12. Noninvasive k3 estimation method for slow dissociation PET ligands: application to [11C]Pittsburgh compound B.

    Science.gov (United States)

    Sato, Koichi; Fukushi, Kiyoshi; Shinotoh, Hitoshi; Shimada, Hitoshi; Hirano, Shigeki; Tanaka, Noriko; Suhara, Tetsuya; Irie, Toshiaki; Ito, Hiroshi

    2013-11-16

    Recently, we reported an information density theory and an analysis of three-parameter plus shorter scan than conventional method (3P+) for the amyloid-binding ligand [11C]Pittsburgh compound B (PIB) as an example of a non-highly reversible positron emission tomography (PET) ligand. This article describes an extension of 3P + analysis to noninvasive '3P++' analysis (3P + plus use of a reference tissue for input function). In 3P++ analysis for [11C]PIB, the cerebellum was used as a reference tissue (negligible specific binding). Fifteen healthy subjects (NC) and fifteen Alzheimer's disease (AD) patients participated. The k3 (index of receptor density) values were estimated with 40-min PET data and three-parameter reference tissue model and were compared with that in 40-min 3P + analysis as well as standard 90-min four-parameter (4P) analysis with arterial input function. Simulation studies were performed to explain k3 biases observed in 3P++ analysis. Good model fits of 40-min PET data were observed in both reference and target regions-of-interest (ROIs). High linear intra-subject (inter-15 ROI) correlations of k3 between 3P++ (Y-axis) and 3P + (X-axis) analyses were shown in one NC (r2 = 0.972 and slope = 0.845) and in one AD (r2 = 0.982, slope = 0.655), whereas inter-subject k3 correlations in a target region (left lateral temporal cortex) from 30 subjects (15 NC + 15 AD) were somewhat lower (r2 = 0.739 and slope = 0.461). Similar results were shown between 3P++ and 4P analyses: r2 = 0.953 for intra-subject k3 in NC, r2 = 0.907 for that in AD and r2 = 0.711 for inter-30 subject k3. Simulation studies showed that such lower inter-subject k3 correlations and significant negative k3 biases were not due to unstableness of 3P++ analysis but rather to inter-subject variation of both k2 (index of brain-to-blood transport) and k3 (not completely negligible) in the reference region. In [11C]PIB, the applicability of 3

  13. Bis{μ-2,2′-[1,1′-(ethane-1,2-diyldinitrilodiethylidyne]diphenolato-κ5O,N,N′,O′:O}bis[chloridomanganese(III

    Directory of Open Access Journals (Sweden)

    Robert D. Pike

    2008-02-01

    Full Text Available The title compound, [Mn2(C18H18N2O22Cl2], was synthesized by the reaction between manganese(II o-chlorobenzoate and the Schiff base generated in situ by the condensation of ethane-1,2-diamine and o-hydroxyacetophenone. The centrosymmetric dimer contains two Jahn–Teller-distorted manganese(III ions, each in an octahedral geometry, connected through two phenoxy bridges from two ligands.

  14. Tris(dibenzoylmethanido-κ2O,O′[(6S,8S-(+-7,7-dimethyl-3-(2-pyridyl-5,6,7,8-tetrahydro-6,8-methanoisoquinoline-κ2N,N′]gadolinium(III

    Directory of Open Access Journals (Sweden)

    Xi-Li Li

    2009-09-01

    Full Text Available In the title compound, [Gd(C15H11O23(C17H18N2], the GdIII atom is coordinated by six O atoms from three β-diketonate ligands and two N atoms from a chiral ligand LS,S-(+-7,7-dimethyl-3-(2-pyridyl-5,6,7,8-tetrahydro-6,8-methanoisoquinoline, in a coordination geometry best described as distorted square-antiprismatic.

  15. (2-Pyridyl[5-(2-pyridylcarbonyl-2-pyridyl]methanone

    Directory of Open Access Journals (Sweden)

    Zi-jia Wang

    2010-10-01

    Full Text Available In the centrosymmetric title compound, C17H11N3O2, the dihedral angle between the central and pendant pyridyl rings is 50.29 (9°. In the crystal, molecules stack along the a axis by π–π interactions between the pyridine rings with centroid–centroid distances of 3.845 (2 Å. The N atom and one of the C atoms of the central ring are disordered by symmetry.

  16. 1,4,8,11-Tetra[2-aryl-1-diazenyl]-1,4,8,11-tetraazacyclotetradecanes - synthesis, characterization, and x-ray crystallography of the first tetrakistriazenes to be reported

    Energy Technology Data Exchange (ETDEWEB)

    Clarke, J.D.; Vaughan, K. [Dept. of Chemistry, Saint Mary' s Univ., Halifax, Nova Scotia (Canada)], E-mail: keith.vaughan@smu.ca; Bertolasi, V. [Dipartimento di Chimica and Centro di Strutturistica Diffrattometrica, Universita' di Ferrara, Ferrara (Italy)

    2006-10-15

    The reactions of a series of arene diazonium salts with 1,4,8,11-tetraazacyclotetradecane (cyclam) afford the novel compounds, the 1,4,8,11-tetra[2-aryl-1-diazenyl]-1,4,8,11-tetraazacyclotetradecanes (1a-1f), which are the first examples of tetrakistriazenes to be reported. The tetrakistriazenes were characterized by IR spectroscopy, proton and carbon NMR, elemental analysis, high resolution electrospray mass spectrometry, and X-ray crystallography. The analogous reaction of a diazonium salt with 1,4,7-triazacyclononane or 1,5,9-triazacyclododecane yields the tristriazenes 2, 3a, and 3b. The structures of compounds 1c and 1e were solved by X-ray crystallography at low temperature (150 K). Both molecules display a conformation where the four phenyltriazenyl groups point alternately upwards and downwards with respect to the mean macrocyclic plane. (author)

  17. 1,4,8,11-Tetra[2-aryl-1-diazenyl]-1,4,8,11-tetraazacyclotetradecanes - synthesis, characterization, and x-ray crystallography of the first tetrakistriazenes to be reported

    International Nuclear Information System (INIS)

    Clarke, J.D.; Vaughan, K.; Bertolasi, V.

    2006-01-01

    The reactions of a series of arene diazonium salts with 1,4,8,11-tetraazacyclotetradecane (cyclam) afford the novel compounds, the 1,4,8,11-tetra[2-aryl-1-diazenyl]-1,4,8,11-tetraazacyclotetradecanes (1a-1f), which are the first examples of tetrakistriazenes to be reported. The tetrakistriazenes were characterized by IR spectroscopy, proton and carbon NMR, elemental analysis, high resolution electrospray mass spectrometry, and X-ray crystallography. The analogous reaction of a diazonium salt with 1,4,7-triazacyclononane or 1,5,9-triazacyclododecane yields the tristriazenes 2, 3a, and 3b. The structures of compounds 1c and 1e were solved by X-ray crystallography at low temperature (150 K). Both molecules display a conformation where the four phenyltriazenyl groups point alternately upwards and downwards with respect to the mean macrocyclic plane. (author)

  18. 3-[(2,4-Dichlorophenyliminomethyl]-2-hydroxy-5-methylbenzaldehyde

    Directory of Open Access Journals (Sweden)

    Işın Kılıç

    2009-06-01

    Full Text Available The title compound, C15H11Cl2NO2, is a Schiff base which adopts the phenol–imine tautomeric form in the solid state, being stabilized by a strong intramolecular O—H...N hydrogen bond. The molecule is almost planar (r.m.s. deviation for all non-H atoms = 0.049 Å, displaying a dihedral angle of 3.1 (3° between the planes of the two aromatic rings.

  19. Synthesis and PET studies of [{sup 11}C-cyano]letrozole (Femara), an aromatase inhibitor drug

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Kun-Eek [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States); Biegon, Anat [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ding, Yu-Shin [Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Fischer, Andre [Johannes-Gutenberg Universitaet Mainz, Institut fuer Organische Chemie, 55128 Mainz (Germany); Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States)], E-mail: fowler@bnl.gov

    2009-02-15

    Introduction: Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K{sub i}=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods: Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [{sup 11}C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [{sup 11}C-cyano]letrozole fraction in arterial plasma were also measured. Results: [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16{+-}2.21 Ci/{mu}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. Conclusion: [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity

  20. Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

    Science.gov (United States)

    Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

    2011-01-01

    Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain

  1. Thermogravimetric analysis, kinetic study, and pyrolysis-GC/MS analysis of 1,1'-azobis-1,2,3-triazole and 4,4'-azobis-1,2,4-triazole.

    Science.gov (United States)

    Jia, Chenhui; Li, Yuchuan; Zhang, Shujuan; Fei, Teng; Pang, Siping

    2018-03-01

    In general, the greater the number of directly linked nitrogen atoms in a molecule, the better its energetic performance, while the stability will be accordingly lower. But 1,1'-azobis-1,2,3-triazole (1) and 4,4'-azobis-1,2,4-triazole (2) show remarkable properties, such as high enthalpies of formation, high melting points, and relatively high stabilities. In order to rationalize this unexpected behavior of the two compounds, it is necessary to study their thermal decompositions and pyrolyses. Although a great deal of research has been focused on the synthesis and characterization of energetic materials with 1 and 2 as the backbone, a complete report on their fundamental thermodynamic parameters and thermal decomposition properties has not been published. Thermogravimetric-differential scanning calorimetry were used to obtain the thermal decomposition data of the title compounds. Kissinger and Ozawa-Doyle methods, the two selected non-isothermal methods, are presented for analysis of the solid-state kinetic data. Pyrolysis-gas chromatography/mass spectrometry was used to study the pyrolysis process of the title compounds. The DSC curves show that the thermal decompositions of 1 and 2 are at different heating rates involved a single exothermic process. The TG curves provide insight into the total weight losses from the compounds associated with this process. At different pyrolysis temperatures, the compositions and types of the pyrolysis products differ greatly and the pyrolysis reaction at 500 °C is more thorough than 400 °C. Apparent activation energies (E) and pre-exponential factors (lnA/s -1 ) are 291.4 kJ mol -1 and 75.53 for 1; 396.2 kJ mol -1 and 80.98 for 2 (Kissinger). The values of E are 284.5 kJ mol -1 for 1 and 386.1 kJ mol -1 for 2 (Ozawa-Doyle). The critical temperature of thermal explosion (T b ) is evaluated as 187.01 °C for 1 and 282.78 °C for 2. The title compounds were broken into small fragment ions under the pyrolysis conditions

  2. Towards the total synthesis of stawamycin. Synthesis of C11-C21 fragment.

    OpenAIRE

    Dias, LC; Jardim, LSA; Ferreira, AA; Soarez, HU

    2001-01-01

    The carbocyclic (C11-C21) fragment of Stawamycin has been prepared by a sequence involving 11 steps (10% overall yield) from methyl (R)-(-)-3-hydroxy-2-methylpropionate. Key steps are Pd-catalyzed Stille coupling reaction between a vinyl iodide and a vinylstannane followed by an intramolecular Diels-Alder cycloaddition reaction to afford the desired adduct as the major isomer together with three other possible adducts in 78% overall yield. A porção carbocíclica (C11-C21) da Estavamicina fo...

  3. L-[4-11C]aspartic acid: enzymatic synthesis, myocardial uptake, and metabolism

    International Nuclear Information System (INIS)

    Barrio, J.R.; Egbert, J.E.; Henze, E.; Schelbert, H.R.; Baumgartner, F.J.

    1982-01-01

    Sterile, pyrogen-free L-[4- 11 C]aspartic acid was prepared from 11 CO 2 using phosphoenolpyruvate carboxylase and glutamic/oxaloacetic acid transaminase immobilized on Sepharose supports to determine if it is a useful indicator for in vivo, noninvasive determination of myocardial metabolism. An intracoronary bolus injection of L-[4- 11 C]aspartic acid into dog myocardium showed a triexponential clearance curve with maximal production of 11 CO 2 100 s after injection. Inactivation of myocardial transaminase activity modified the tracer clearance and inhibited the production of 11 CO 2 . Positron-computed tomography imaging showed that the 11 C activities retained in rhesus monkey myocardium are higher than those observed in dog heart after intravenous injection of L-[4- 11 C]aspartic acid. These findings demonstrated the rapid incorporation of the carbon skeleton of L-aspartic acid into the tricarboxylic acid cycle after enzymatic transamination in myocardium and suggested that L-[4- 11 C]aspartic acid could be of value for in vivo, noninvasive assessment of local myocardial metabolism

  4. Di-?-cyanido-tetra?cyanido(5,5,7,12,12,14-hexa?methyl-1,4,8,11-tetra?aza?cyclo?tetra?decane)[N-(quinolin-8-yl)quinoline-2-carboxamidato]diiron(III)nickel(II) 2.07-hydrate

    OpenAIRE

    Yang, Yuqi; Zhou, Hongbo; Shen, Xiaoping

    2013-01-01

    The asymmetric unit of the title complex, [Fe2Ni(C19H12N3O)2(CN)6(C16H36N4)]?2.07H2O, contains one [Fe(qcq)(CN)3]? anion, half a [Ni(teta)]2+ cation and two partially occupied inter?stitial water mol?ecules [qcq? is the N-(quinolin-8-yl)quinoline-2-carboxamidate anion and teta is 5,5,7,12,12,14-hexa?methyl-1,4,8,11-tetra?aza?cyclo?tetra?deca?ne]. In the complex mol?ecule, two [Fe(qcq)(CN)3]? anions additionally coordinate the central [Ni(teta)]2+ cation through cyanide groups in a trans mode,...

  5. 2,4-Dichloro-N-o-tolylbenzamide

    Directory of Open Access Journals (Sweden)

    Aamer Saeed

    2009-07-01

    Full Text Available In the title compound, C14H11Cl2NO, the central C—C(O—N—C amide unit makes dihedral angles of 68.71 (11 and 54.92 (12°, respectively, with the dichlorobenzene and tolyl rings. The two aromatic rings are inclined at 16.25 (17°. In the crystal, N—H...O hydrogen bonds link molecules into zigzag chains propagating in [001]. C—H...Cl contacts link these chains and additional C—H...O contacts generate stacks down b. Weak C—H...π and C—Cl...π interactions [Cl...centroid distance = 3.5422 (15 Å] may also stabilize the structure.

  6. Detailed NMR, Including 1,1-ADEQUATE, and Anticancer Studies of Compounds from the Echinoderm Colobometra perspinosa

    Directory of Open Access Journals (Sweden)

    Catherine H. Liptrot

    2009-11-01

    Full Text Available From the dichloromethane/methanol extract of the crinoid Colobometra perspinosa, collected south east of Richards Island (Bedara, Family Islands, Central Great Barrier Reef, Australia, 3-(1'-hydroxypropyl-1,6,8-trihydroxy-9,10-anthraquinone [one of the two stereoisomers of rhodoptilometrin, (1], 3-propyl-1,6,8-trihydroxy-9,10-anthraquinone (3, 2-[(phenylacetylamino]ethanesulfonic acid (4, and 4-hydroxybutanoic acid (5 were isolated. Comparison of 1H- and 13C-NMR data for rhodoptilometrin (1 with those reported in the literature showed significant differences for some resonances associated with rings A and C. In an attempt to provide accurately assigned 1H- and 13C-NMR data, as well as to confirm the structure of 1, a thorough NMR investigation of this compound was undertaken. Measurements included: concentration dependent 13C, 1D selective NOE, HSQC, HMBC and 1,1-ADEQUATE. The NMR data for 4 and 5 are reported here for the first time, as is their occurrence from the marine environment. The in vitro anticancer activity of the original extract was found to be associated with 1, 3 and 5.

  7. (N,N,N′,N′-Tetramethylethylenediamine-κNbis(2,4,6-trimethylphenolato-κOgermanium(II

    Directory of Open Access Journals (Sweden)

    Eduard Rusanov

    2012-03-01

    Full Text Available In the title compound, [Ge(C9H11O2(C6H16N2], the GeII atom is coordinated in a distorted trigonal–pyramidal geometry by two O atoms belonging to two 2,4,6-trimethylphenolate ligands and one N atom of a tetramethylethylenediamine ligand. Comparing the structure with published data of similar compounds shows that the Ge—O bonds are covalent and the Ge—N bond is coordinated.

  8. Labeling of complex molecules with 18F, 13N, and 11C

    International Nuclear Information System (INIS)

    Brownell, G.L.; Elmaleh, D.R.

    1980-01-01

    The overall objective during the period covered by this report was to develop a broad spectrum of radiopharmaceuticals labeled with short-lived cyclotron positron emitters, 11 C, 13 N and 18 F. The goals of the program during the last year were: (1) to complete the modular automated system for important precursor production - formaldehyde, methyliodide, cyanide; (2) to perform animal studies with the 18 F-glucose analogues 2FDG and 3FDG and measure the constants for both agents in different animals; and (3) to initiate the development of new fatty acid analogues for the myocardial imaging and metabolism. As part of a collaboration with other groups seeking new agents for myocardium and brain, 9-/sup 123m/Te-telluriumheptadecanoic acid as a myocardial imaging agent was studied. This compound could be used for designing new fatty acid analogues labeled with 11 C and 18 F that stay in the myocardium because of metabolic inhibition

  9. Preparation of a 1:1 cocrystal of genistein with 4,4‧-bipyridine

    Science.gov (United States)

    Zhang, Yu-Nan; Yin, He-Mei; Zhang, Yu; Zhang, Da-Jun; Su, Xin; Kuang, Hai-Xue

    2017-01-01

    Based on analysing the relationship between the possible number of intermolecular O-H···N hydrogen bonds and the stoichiometric ratio, a 1:1 C15H10O5·C10H8N2 (genistein-4,4‧-bipyridine) cocrystal has been prepared by solution evaporation and characterized. This work successfully demonstrates that the stoichiometric ratio could be inferred by analysing the possible number of intermolecular hydrogen bonds between flavonoids and amines. The strategy provides a facile route for rational designing cocrystal of flavonoids with amines. Additionally, the title cocrystal shows advantages in terms of solubility and antibacterial properties in comparison to pure genistein.

  10. (2E-3-(4-Chlorophenyl-1-(4-hydroxyphenylprop-2-en-1-one

    Directory of Open Access Journals (Sweden)

    Jerry P. Jasinski

    2011-04-01

    Full Text Available In the title compound, C15H11ClO2, the dihedral angle between the mean planes of the chlorobenzene and hydroxybenzene rings is 6.5 (6°. The mean plane of the prop-2-en-1-one group makes an angle of 18.0 (1° with the hydroxyphenyl ring and 11.5 (1° with the chlorophenyl ring. The crystal packing is stabilized by intermolecular O—H...O hydrogen bonds, weak C—H...O, C—H...π and π–π stacking interactions [centroid–centroid distances = 3.7771 (7 and 3.6917 (7 Å].

  11. The study of methanol transformation over Cu-modified ZSM-5, Beta zeolite and MCM-41 mesoporous silica using 11C-radioisotope labeling

    International Nuclear Information System (INIS)

    Sarkadi-Priboczki, E.; Kovacs, Z.

    2004-01-01

    Complete text of publication follows. The copper-containing zeolites and mesoporous silica, among other metals, are suitable for dehydrogenation of methanol. The Cu transition metal determines the route of methanol conversion on supports of ZSM-5 and Beta zeolite as well as MCM-41 mesoporous silica. The catalysis mechanism and the catalytic property are concluded from the composition of methanol derivates over Cu-modified catalysts. The Cu ion-exchanged ZSM-5 and Beta zeolite and MCM-41 mesoporous silica were synthesized and characterized using X-ray power diffraction, scanning electron microscope, nitrogen and pyridine adsorption, X-ray fluorescency and FTIR spectroscopy. The 11 C-radioactive labeling method ( 11 C radioisotope, T 1/2 = 20 min, is a gamma emitter by annihilation of its positron) is suitable for following the process of 11 C-methanol con- version i.e. adsorption, desorption and catalytic transformation as well as for investigation of small amounts of molecules over catalysts by very sensitive radioactivity detectors.The 11 C radioisotope was produced at cyclotron and the 11 C-methanol was synthesized by a classical radiochemical method. After catalysis the 11 C-radioactive and non radioactive volatile products were identified by radiogas chromatography hereby radiolabeled compound and -derivates were distinguished from other participant natural, nonradioactive carbon compounds. Along radioactive products dimethyl ether and small hydrocarbons products were formed by Bronsted acid sites of catalysts while formaldehyde and small methyl formate were formed by Cu metal over bifunctional Cu-ZSM-5, Cu-Beta zeolite and mesoporous Cu-MCM-41 silica at 240 deg C. The detection of methoxy methanol and dimethoxy methane confirmed the simultaneous presence of acid and basic sites of catalysts. At higher temperature (400 deg C) the CO and CO 2 final products were dominated. In our previous works, methanol conversion to hydrocarbons was observed by dehydration

  12. Synthesis of carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolinium derivatives as new potential PET SK{sub Ca} channel imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Gao Mingzhang; Wang Min [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

    2008-02-15

    Small conductance Ca{sup 2+}-activated K{sup +} (SK{sub Ca}) channels play an important role in many functions such as neuronal communication and behavioral plasticity, secretion, and cell proliferation. SK{sub Ca} channel modulation is associated with various brain, heart, and cancer diseases. N-methyl-laudanosine and its structurally related derivatives, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums, are reversible and selective SK{sub Ca} channel blockers. Carbon-11 labeled N-methyl-laudanosine and its tetrahydroisoquinolinium derivatives may serve as new probes for positron emission tomography (PET) to image SK{sub Ca} channels in the brain, heart, and cancer. The key intermediates, substituted isoquinolines (3a-c), were synthesized using a modification of the Pomeranz-Fritsch procedure. The precursors, substituted 1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolines (8a-c), and their corresponding reference standards, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums (9a-c), were synthesized from compounds 3a-c with 3,4-dimethoxybenzyl chloride (2) in multiple steps with moderate to excellent chemical yields. The precursor 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3, 4-tetrahydroisoquinoline (10) was commercially available, and the methylation of compound 10 with methyl iodide provided N-methyl-laudanosine (11). The target quaternary ammonium tracers, carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums ([{sup 11}C]9a-c and [{sup 11}C]11), were prepared by N-[{sup 11}C]methylation of the tertiary amine precursors (8a-c and 10) with [{sup 11}C]methyl triflate and isolated by a simplified solid-phase extraction (SPE) purification using a SiO{sub 2} or cation-exchange CM Sep-Pak cartridge in 40-65% radiochemical yields.

  13. Biodistribution and radiation dosimetry of {sup 11}C-labelled docetaxel in cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Veldt, Astrid A.M. van der; Mooijer, Martien P.J.; Rijnders, Anneloes Y.; Windhorst, Albert D.; Lammertsma, Adriaan A.; Lubberink, Mark [VU University Medical Center, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); Hendrikse, N.H. [VU University Medical Center, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Clinical Pharmacology and Pharmacy, Amsterdam (Netherlands); Smit, Egbert F. [VU University Medical Center, Department of Pulmonology, Amsterdam (Netherlands); Gerritsen, Winald R. [VU University Medical Center, Department of Medical Oncology, Amsterdam (Netherlands); Hoeven, Jacobus J.M. van der [Medical Center Alkmaar, Department of Internal Medicine, Alkmaar (Netherlands)

    2010-10-15

    Docetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter {sup 11}C. Non-invasive measurements of [{sup 11}C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [{sup 11}C]docetaxel in humans. Biodistribution of [{sup 11}C]docetaxel was measured in seven patients (five men and two women) with solid tumours using PET/CT. Venous blood samples were collected to measure activity in blood and plasma. Regions of interest (ROI) for various source organs were defined on PET (high [{sup 11}C]docetaxel uptake) or CT (low [{sup 11}C]docetaxel uptake). ROI data were used to generate time-activity curves and to calculate percentage injected dose and residence times. Radiation absorbed doses were calculated according to the MIRD method using OLINDA/EXM 1.0 software. Gall bladder and liver demonstrated high [{sup 11}C]docetaxel uptake, whilst uptake in brain and normal lung was low. The percentage injected dose at 1 h in the liver was 47 {+-} 9%. [{sup 11}C]docetaxel was rapidly cleared from plasma and no radiolabelled metabolites were detected. [{sup 11}C]docetaxel uptake in tumours was moderate and highly variable between tumours. The effective dose of [{sup 11}C]docetaxel was 4.7 {mu}Sv/MBq. As uptake in normal lung is low, [{sup 11}C]docetaxel may be a promising tracer for tumours in the thoracic region. (orig.)

  14. 11C-acetate PET imaging in patients with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Kazushiro Takata

    Full Text Available BACKGROUND: Activation of glial cells is a cardinal feature in multiple sclerosis (MS pathology, and acetate has been reported to be selectively uptaken by astrocytes in the CNS. The aim of this study was to investigate the efficacy of PET with (11C-acetate for MS diagnosis. MATERIALS AND METHODS: Six patients with relapsing-remitting MS and 6 healthy volunteers (HV were enrolled. The (11C-acetate brain uptake on PET was measured in patients with MS and HV. Volume-of-interest analysis of cerebral gray and white matter based on the segmentation technique for co-registered MRI and voxel-based statistical parametric analysis were performed. Correlation between 11C-acetate uptake and the lesion number in T1- and T2- weighted MR images were also assessed. RESULTS: The standardized uptake value (SUV of 11C-acetate was increased in both white and gray matter in MS patients compared to HV. Voxel-based statistical analysis revealed a significantly increased SUV relative to that in the bilateral thalami (SUVt in a broad area of white matter, particularly in the subcortical white matter of MS patients. The numbers of T2 lesions and T1 black holes were significantly correlated with SUV of (11C-acetate in white and gray matter. CONCLUSIONS: The 11C-acetate uptake significantly increased in MS patients and correlated to the number of MRI lesions. These preliminary data suggest that (11C-acetate PET can be a useful clinical examination for MS patients.

  15. A novel approach for a C-11C bond formation: synthesis of 17α-([11C]prop-1-ynyl)-3-methoxy-3,17β-estradiol

    International Nuclear Information System (INIS)

    Wuest, F.; Zessin, J.

    2002-01-01

    A novel method for a 11 C-C bond formation was developed, employing a cross-coupling reaction between a terminal acetylene and [ 11 C]methyl iodide. The method was used for the synthesis of 17α-([ 11 C]prop-1-ynyl)-3-methoxy-3,17β-estadiol. (orig.)

  16. Crystal structure of catena-poly[[aqua(2,2′:6′,2′′-terpyridine-κ3N,N′,N′′cobalt(II]-μ-cyanido-κ2N:C-[dicyanidoplatinum(II]-μ-cyanido-κ2C:N

    Directory of Open Access Journals (Sweden)

    Frankie White

    2014-09-01

    Full Text Available The title compound, [Co(C15H11N3(H2O{Pt(CN4}]n, is a one-dimensional coordination polymer formed under hydrothermal reaction conditions. The CoII site has sixfold coordination with a distorted octahedral geometry, while the PtII ion is coordinated by four cyanide groups in an almost regular square-planar geometry. The compound contains twofold rotation symmetry about its CoII ion, the water molecule and the terpyridine ligand, and the PtII atom resides on an inversion center. trans-Bridging by the tetracyanidoplatinate(II anions links the CoII cations, forming chains parallel to [-101]. Additionally, each CoII atom is coordinated by one water molecule and one tridentate 2,2′:6′,2′′-terpyridine ligand. O—H...N hydrogen-bonding interactions are found between adjacent chains and help to consolidate the crystal packing. In addition, relatively weak π–π stacking interactions exist between the terpyridine ligands of adjacent chains [interplanar distance = 3.464 (7 Å]. No Pt...Pt interactions are observed in the structure.

  17. In-beam γ-ray spectroscopy of N=84 nuclei above Gd and the impact of the (πh11/2νh9/2)1+ attraction on their yrast lines

    International Nuclear Information System (INIS)

    Zhang Chengteng.

    1993-12-01

    In in-beam experiments using the γ-spectrometers Nordball at the Niels Bohr Institute and Osiris at the Hahn-Meitner Institute we populated the four N = 84 isotones 151 Ho, 152 Er, 153 Tm and 154 Yb through compound evaporation reactions induced with medium HI beams of masses ranging from 28 to 56. All observed γ-transitions with intensities above 1% (5% in 154 Yb) of the respective exit channel were placed in the level schemes, with spins established up to 10 MeV (8 MeV for 154 Yb) and parties up to between 5 and 7 MeV. We have found that in these N = 84 nuclei the multi-valence particle configurations πh n 11/2 νf 2 7/2 and πh n 11/2 νf 7/2 h 9/2 are strongly populated in the yrast cascades, and we have observed them up to their maximum spins of 43/2 - in Ho (at 4.8 MeV), 24 + in Er (7.5 MeV), 51/2 - in Tm (6.9 MeV), and only up to 24 + in Yb, 0.5 MeV below the fully aligned 26 + state expected at 9.1 MeV. The πh n νf 2 configuration forms smooth sections of the yrast line, while the more irregular yrast line of the πh n νfh character reflects the strong (νfh)8 + two-body attraction which gives rise to pronounced yrast line dips. We have also carried out full shell model calculations of these yrast lines, which are in excellent agreement with the experimental data. Since we take all dynamic input values, i.e. the two-body matrix elements and the single particle energies, from experiment, the calculations are free of any adjusted parameter. An interesting new result is the systematic identification in the πh n 11/2 νfh configuration of yrast states formed by specific proton couplings, where the strongly attractive (πh 11/2 νh 9/2 )1 + interaction is activated. As a consequence these states drop down to the yrast lines and in energy below the maximum aligned state of the next lower proton seniority. These seniority inverted yrast states were systematically identified in the four N = 84 nuclei, including two such states in 153 T, the first N 84

  18. Radiosynthesis of [11C]SB-705498, a selective transient receptor potential Vanilloid 1 (TRPV1) receptor antagonist

    International Nuclear Information System (INIS)

    Dolle, F.; Bramoulle, Y.; Deverre, J.R.; Bottlaender, M.; Passchier, J.

    2011-01-01

    column (eluent: H 2 O / CH 3 CN / TFA: 72 / 28 / 0.1 (v/v/v) - flowrate: 8 mL/min), and finally (D) removal of the HPLC solvents using a SepPak R Plus C18 device (recovery of [ 11 C]SB-705498 ([ 11 C]-1) as ethanol solution), sterile-filtration (Millex FG 0.22 μm filter, Millipore) and final formulation as an i.v. injectable solution. Results: [ 11 C]SB-705498 ([ 11 C]-1) was obtained in 8.9-13.6% non-decay-corrected yields, based on starting [ 11 C]methane. Starting from a 26 GBq cyclotron-produced [ 11 C]methane batch, 2.3 to 3.5 GBq of [ 11 C]SB-705498 ([ 11 C]-1), ≥ 99% radiochemically pure and ready-to-inject, were obtained in a one-pot two-step process within 30 minutes (including HPLC-purification, Rt: 9-10 min, and formulation). Specific radioactivities ranged from 75 to 150 GBq/μmol. Conclusions: SB-705498 (1) was isotopically labelled with carbon-11 at its urea function using [ 11 C]phosgene. The non-decay-corrected overall yields for the preparation of [ 11 C]SB-705498 were 8.9%-13.6%. Dynamic PET studies in baboons are currently underway to evaluate the potential of [ 11 C]SB-705498 to image central transient receptor potential Vanilloid 1 (TRPV1) receptor in vivo

  19. {sup 11}C- and {sup 18}F Production at TPC RK2 Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Solin, O.; Johansson, S.; Eriksson, P-O.; Rajander, J.; Kokkomäki, E.; Helin, S.; Arponen, E.; Aromaa, J.; Savisto, N.; Bergman, J.; Heselius, S-J. [Turku PET Centre, Radiopharmaceutical Chemistry Laboratory and Accelerator Laboratory, Porthaninkatu 3, 20500 Turku (Finland)

    2009-07-01

    Four gas targets for production of [{sup 11}C]CO{sub 2} and [{sup 11}C]CH{sub 4} as well as static and one circulating water target for [{sup 18}F]fluoride production have been installed on the external beam line of the CC18/9 cyclotron (Efremov Institute for Electrophysical Apparatuses, St. Petersburg, Russia) at TPC. The cyclotron is capable of accelerating 18 MeV protons (9 MeV deuterons) at particle beam intensities in excess of 100 μA. The aim with these radionuclide production systems is high yield, high specific radioactivity precursor production for PET radiopharmaceuticals.

  20. Evaluation of [{sup 11}C]rofecoxib as PET tracer for cyclooxygenase 2 overexpression in rat models of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Erik F.J. de [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen (Netherlands)], E-mail: e.f.j.de.vries@ngmb.umcg.nl; Doorduin, Janine; Dierckx, Rudi A.; Waarde, Aren van [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen (Netherlands)

    2008-01-15

    Background: Overexpression of cyclooxygenase type 2 (COX-2) is triggered by inflammatory stimuli, but it also plays a prominent role in the initiation and progression of various diseases. This study aims to investigate [{sup 11}C]rofecoxib as a positron emission tomography (PET) tracer for COX-2 expression. Methods: [{sup 11}C]Rofecoxib was prepared by methylation of its sulphinate precursor. Regional brain distribution and specific binding of [{sup 11}C]rofecoxib in healthy rats was studied by ex vivo biodistribution and autoradiography. Regional brain distribution and PET imaging studies were also performed on rats with severe encephalitis, caused by nasal infection with herpes simplex virus (HSV). Finally, ex vivo biodistribution and blocking studies were carried in rats with a sterile inflammation, induced by intramuscular turpentine injection. Results: [{sup 11}C]rofecoxib brain uptake in control animals corresponded with the known distribution of COX-2. Pretreatment with NS398 significantly reduced tracer uptake in the cingulate/frontopolar cortex, whereas the reduction in hippocampus approached significance. Ex vivo autoradiography also revealed preferential tracer uptake in hippocampus and cortical areas that could be blocked by NS398. In HSV-infected animals, [{sup 11}C]rofecoxib uptake was moderately increased in all brain regions, but it could not be blocked with indomethacin. Yet, some PET images revealed increased tracer uptake in brain areas with microglia activation. In turpentine-injected animals, [{sup 11}C]rofecoxib uptake in inflamed muscle was not higher than in control muscle and could not be blocked with NS398. Indomethacin caused a slight reduction in muscle uptake. Conclusions: Despite the apparent correlation between [{sup 11}C]rofecoxib uptake and COX-2 distribution in healthy rats, [{sup 11}C]rofecoxib could not unambiguously detect COX-2 overexpression in two rat models of inflammation.

  1. 10-Benzyl-10H-phenothiazine 9-oxide

    Directory of Open Access Journals (Sweden)

    Zhouqing Xu

    2009-08-01

    Full Text Available In the title compound, C19H15NOS, the butterfly angle between the mean planes defined by the S, N and phenyl C atoms of the two wings of the phenothiazine unit is 23.4 (1°. In the crystal, a supramolecular two-dimensional arrangement arises from weak intermolecular C—H...O interactions.

  2. 1,2,3,4,6 Penta-O-galloyl-β-d-glucose, a bioactivity guided isolated compound from Mangifera indica inhibits 11β-HSD-1 and ameliorates high fat diet-induced diabetes in C57BL/6 mice.

    Science.gov (United States)

    Mohan, C G; Viswanatha, G L; Savinay, G; Rajendra, C E; Halemani, Praveen D

    2013-03-15

    Methanolic leaf extract of Mangifera indica (MEMI) was subjected to bioactivity guided fractionation in order to identify the active antidiabetic constituent. 32 fractions were evaluated for possible 11β-HSD-1 inhibition activity under in vitro conditions. The EA-7/8-9/10-4 fraction was evolved as a most potent fraction among all the fractions and it was identified as well known gallotannin compound 1,2,3,4,6 penta-O-galloyl-β-d-glucose (PGG) by spectral analysis. Based on these results the PGG was further evaluated in ex vivo 11β-HSD-1 inhibition assay and high fat diet (HFD)-induced diabetes in male C57BL/6 mice. Single dose (10, 25, 50 and 100mg/kg) of PGG and carbenoxolone (CBX) have dose dependently inhibited the 11β-HSD-1 activity in liver and adipose tissue. Furthermore, HFD appraisal to male C57BL/6 mice caused severe hyperglycemia, hypertriglyceridemia, elevated levels of plasma corticosterone and insulin, increased liver and white adipose mass with increase in body weight was observed compare to normal control. Also, oral glucose tolerance was significantly impaired compare to normal control. Interestingly, post-treatment with PGG for 21 days had alleviated the HFD-induced biochemical alterations and improved oral glucose tolerance compare to HFD-control. In conclusion, the PGG isolated from MEMI inhibits 11β-HSD-1 activity and ameliorates HFD-induced diabetes in male C57BL/6 mice. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Elimination mechanisms of Br2+ and Br+ in photodissociation of 1,1- and 1,2-dibromoethylenes using velocity imaging technique

    International Nuclear Information System (INIS)

    Hua Linqiang; Zhang Bing; Lee, Wei-Bin; Chao, Meng-Hsuan; Lin, King-Chuen

    2011-01-01

    Elimination pathways of the Br 2 + and Br + ionic fragments in photodissociation of 1,2- and 1,1-dibromoethylenes (C 2 H 2 Br 2 ) at 233 nm are investigated using time-of-flight mass spectrometer equipped with velocity ion imaging. The Br 2 + fragments are verified not to stem from ionization of neutral Br 2 , that is a dissociation channel of dibromoethylenes reported previously. Instead, they are produced from dissociative ionization of dibromoethylene isomers. That is, C 2 H 2 Br 2 is first ionized by absorbing two photons, followed by the dissociation scheme, C 2 H 2 Br 2 + + hv→Br 2 + + C 2 H 2 . 1,2-C 2 H 2 Br 2 gives rise to a bright Br 2 + image with anisotropy parameter of -0.5 ± 0.1; the fragment may recoil at an angle of ∼66 deg. with respect to the C = C bond axis. However, this channel is relatively slow in 1,1-C 2 H 2 Br 2 such that a weak Br 2 + image is acquired with anisotropy parameter equal to zero, indicative of an isotropic recoil fragment distribution. It is more complicated to understand the formation mechanisms of Br + . Three routes are proposed for dissociation of 1,2-C 2 H 2 Br 2 , including (a) ionization of Br that is eliminated from C 2 H 2 Br 2 by absorbing one photon, (b) dissociation from C 2 H 2 Br 2 + by absorbing two more photons, and (c) dissociation of Br 2 + . Each pathway requires four photons to release one Br + , in contrast to the Br 2 + formation that involves a three-photon process. As for 1,1-C 2 H 2 Br 2 , the first two pathways are the same, but the third one is too weak to be detected.

  4. Development of miniature module for [11C] methionine synthesis

    International Nuclear Information System (INIS)

    Watanabe, Toshimitsu; Araya, Hiroshi; Ueno, Satoshi

    2006-01-01

    [ 18 F]FDG-PET has spread rapidly in the cancer diagnosis. On the other hand, [ 11 C]Methionine is paid attention as one of the PET drugs that may help cancer diagnosis by [ 18 F]FDG. Due to its short half-life, repeated preparations of [ 11 C] Methionine, two or three times a day, are generally required for the routine PET practice. Although the automatic synthesis devices for [ 11 C]Methionine were developed, it was difficult to supply [ 11 C]Methionine two times a day or more. We developed a methionine synthesis system that was able to supply [ 11 C]Methionine two times a day or more, and a new methionine synthesis unit. The new synthesis unit is able to synthesize [ 11 C]Methionine efficiently without HPLC preparation and evaporation in a short time. The new methionine synthesis unit and system are more useful for the routine synthesis of [ 11 C]Methionine. (author)

  5. A radiometabolite study of the serotonin transporter PET radioligand [11C]MADAM

    International Nuclear Information System (INIS)

    Gourand, F.; Emond, P.; Bergström, J.P.; Takano, A.; Gulyás, B.; Guilloteau, D.; Barré, L.; Halldin, C.

    2014-01-01

    Introduction: 11 C]MADAM is a radioligand suitable for PET studies of the serotonin transporter (SERT). Metabolite analysis in human and non-human plasma samples using HPLC separation has shown that [ 11 C]MADAM was rapidly metabolized. A possible metabolic pathway is the S-oxidation which could lead to SOMADAM and SO 2 MADAM. In vitro evaluation of these two potential metabolites has shown that SOMADAM exhibited a good affinity for SERT and a good selectivity for SERT over NET and DAT. Methods: Comparative PET imaging studies in non-human primate brain with [ 11 C]MADAM and [ 11 C]SOMADAM were carried out, and plasma samples were analyzed using reverse phase HPLC. We have explored the metabolism of [ 11 C]MADAM in rat brain with a view to understand its possible interference for brain imaging with PET. Results: PET imaging studies in non-human primate brain using [ 11 C]SOMADAM indicated that this tracer does not bind with high amounts to brain regions known to be rich in SERT. The fraction of [ 11 C]SOMADAM in non-human primate plasma was approximately 5% at 4 min and 1% at 15 min after [ 11 C]MADAM injection. HPLC analysis of brain sample after [ 11 C]MADAM injection to rats demonstrated that [ 11 C]SOMADAM was not detected in the brain. Conclusions: 11 C]SOMADAM is not superior over [ 11 C]MADAM as a SERT PET radioligand. Nevertheless, [ 11 C]SOMADAM has been identified as a minor labeled metabolite of [ 11 C]MADAM measured in monkey plasma. [ 11 C]SOMADAM was not detected in rat brain

  6. 2-[(2-Chlorobenzylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2011-09-01

    Full Text Available In the title compound, C16H13ClN2S, the mean planes fitted through all non-H atoms of the heterocyclic five-membered and the benzene rings are oriented at a dihedral angle of 5.19 (7°. In the crystal, a weak C—H...π interaction occurs, along with weak π–π interactions [cenroid–centroid distance = 3.7698 (11 Å].

  7. 7-Phenoxy-Substituted 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides as Positive Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors with Nanomolar Potency

    DEFF Research Database (Denmark)

    Goffin, Eric; Drapier, Thomas; Larsen, Anja Probst

    2018-01-01

    We report here the synthesis of 7-phenoxy-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides and their evaluation as AMPA receptor positive allosteric modulators (AMPApams). The impact of substitution on the phenoxy ring and on the nitrogen atom at the 4-position was examined. At GluA2......-ray scattering (SAXS) experiments using isolated GluA2 ligand-binding domain (GluA2-LBD) are consistent with binding of one molecule of 11m per dimer interface, contrary to most benzothiadiazine dioxides developed to date. This observation was confirmed by the X-ray structure of 11m bound to GluA2-LBD and by NMR......(Q) expressed in HEK293 cells (calcium flux experiment), the most potent compound was 11m (4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide, EC50 = 2.0 nM). The Hill coefficient in the screening and the shape of the dimerization curve in small-angle X...

  8. Increased macroH2A1.1 expression correlates with poor survival of triple-negative breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Anne-Claire Lavigne

    Full Text Available PURPOSE: Epithelial-Mesenchymal Transition (EMT features appear to be key events in development and progression of breast cancer. Epigenetic modifications contribute to the establishment and maintenance of cancer subclasses, as well as to the EMT process. Whether histone variants contribute to these transformations is not known. We investigated the relative expression levels of histone macroH2A1 splice variants and correlated it with breast cancer status/prognosis/types. METHODS: To detect differential expression of macroH2A1 variant mRNAs in breast cancer cells and tumor samples, we used the following databases: GEO, EMBL-EBI and publisher databases (may-august 2012. We extracted macroH2A1.1/macroH2A1 mRNA ratios and performed correlation studies on intrinsic molecular subclasses of breast cancer and on molecular characteristics of EMT. Associations between molecular and survival data were determined. RESULTS: We found increased macroH2A1.1/macroH2A1 mRNA ratios to be associated with the claudin-low intrinsic subtype in breast cancer cell lines. At the molecular level this association translates into a positive correlation between macroH2A1 ratios and molecular characteristics of the EMT process. Moreover, untreated Triple Negative Breast Cancers presenting a high macroH2A1.1 mRNA ratio exhibit a poor outcome. CONCLUSION: These results provide first evidence that macroH2A1.1 could be exploited as an actor in the maintenance of a transient cellular state in EMT progress towards metastatic development of breast tumors.

  9. [11C]PR04.MZ, a promising DAT ligand for low concentration imaging: synthesis, efficient 11C-O-methylation and initial small animal PET studies

    International Nuclear Information System (INIS)

    Riss, P.J.; Hooker, J.; Alexoff, D.; Kim, Sung-Won; Fowler, J.S.; Roesch, F.

    2009-01-01

    PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [ 11 C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [ 11 C]MeI mediated synthesis of [ 11 C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb 2 CO 3 in DMF in up to 95 ± 5% labelling yield. A preliminary μPET-experiment demonstrates the reversible, highly specific binding of [ 11 C]PR04.MZ in the brain of a male Sprague-Dawley rat.

  10. Study of the unimolecular decompositions of the (C3H6)+2 and (c-C3H6)+2 complexes

    International Nuclear Information System (INIS)

    Tzeng, W.; Ono, Y.; Linn, S.H.; Ng, C.Y.

    1985-01-01

    The major product channels identified in the unimolecular decompositions ofC 3 H + 6 xC 3 H 6 and c-C 3 H + 6 xc-C 3 H 6 in the total energy [neutral (C 3 H 6 ) 2 or (c-C 3 H 6 ) 2 heat of formation plus excitation energy] range of approx.230--450 kcal/mol are C 3 H + 7 +C 3 H 5 , C 4 H + 7 +C 2 H 5 , C 4 H + 8 +C 2 H 4 , and C 5 H + 9 +CH 3 . The measured appearance energy for C 4 H + 7 (9.54 +- 0.04 eV) from (C 3 H 6 ) 2 is equal to the thermochemical threshold for the formation of C 4 H + 7 +C 2 H 5 from (C 3 H 6 ) 2 , indicating that the exit potential energy barrier for the ion--molecule reaction C 3 H + 6 +C 3 H 6 →C 4 H + 7 +C 2 H 5 is negligible. There is evidence that the formations of C 4 H + 7 +C 2 H 4 +H from (C 3 H 6 ) + 2 and (c-C 3 H 6 ) + 2 also proceed with high probabilities when they are energetically allowed. The variations of the relative abundances for C 4 H + 7 ,C 4 H + 8 , and C 5 H + 9 from (C 3 H 6 ) + 2 and (c-C 3 H 6 ) + 2 as a function of ionizing photon energy are in qualitative agreement, suggesting that (C 3 H 6 ) + 2 and (c-C 3 H 6 ) + 2 rearrange to similar C 6 H + 12 isomers prior to fragmentation. The fact that C 6 H + 11 is found to be a primary ion from the unimolecular decomposition of (c-C 3 H 6 ) + 2 but not (C 3 H 6 ) + 2 supports the conclusion that the distribution of C 6 H + 12 collision complexes involved in the C 3 H + 6 +C 3 H 6 reactions is different from that in the cyclopropane ion--molecule reactions

  11. Synthesis of (2-[{sup 11}C]Methoxy)rotenone, a marker of mitochondrial complex I activity

    Energy Technology Data Exchange (ETDEWEB)

    Charalambous, A; Mangner, T J; Kilbourn, M R

    1995-01-01

    Recent studies suggest that defects in the function of the complexes of the electron transport chain might be involved in the pathology of neurological diseases such as mitochondrial encephalopathies, Parkinson's Huntington's and Alzheimer's disease. Rotenone is a potent reversible competitive inhibitor of complex I (NADH-CoQ reductase). To study the possible involvement of complex I in such diseases, we synthesized (2-[{sup 11}C]methoxy)rotenone by [{sup 11}C]alkylation of 2-O-desmethyl rotenone methyl enol ether followed by hydrolysis of the enol ether to the ketone using aqueous trifluoroacetic acid. (2-[{sup 11}C]Methoxy)rotenone was purified by high pressure liquid chromatography (silica gel) and was obtained in 7-10% yields decay corrected to end of bombardment in synthesis times typically shorter than 48 min. Radiochemical purities were over 95% and specific activities averaged 1000 Ci/mmol at end of synthesis.

  12. N-(2,6-Dichlorophenyl-4-methylbenzamide

    Directory of Open Access Journals (Sweden)

    Vinola Z. Rodrigues

    2011-08-01

    Full Text Available In the title compound, C14H11Cl2NO, the two aromatic rings are nearly orthogonal to each other [dihedral angle 79.7 (1°], while the central amide core –NH—C(=O– is nearly coplanar with the benzoyl ring [N—C—C—C torsion angles = −5.5 (3 and 1772. (2°]. In the crystal, intermolecular N—H...O hydrogen bonds link the molecules into C(4 chains propagating in [001].

  13. Crystal structure of 5,5′-dibromo-3,3′-di-tert-butyl-6,6′-dimethylbiphenyl-2,2′-diol

    Directory of Open Access Journals (Sweden)

    Rika Obata

    2015-05-01

    Full Text Available The whole molecule of the title compound, C22H28Br2O2, is generated by twofold rotation symmetry. The dihedral angle of the biphenyl moiety is 85.05 (11°. The hydroxy groups show intramolecular O—H...π interactions without any other hydrogen-bond acceptors. In the crystal, there are no other significant intermolecular interactions present.

  14. Binding kinetics of 11C-N-methyl piperidyl benzilate (11C-NMPB) in a rhesus monkey brain using the cerebellum as a reference region

    International Nuclear Information System (INIS)

    Itoh, Takashi; Tanaka, Masayasu; Suzuki, Kasutoshi; Kobayashi, Kaoru; Inoue, Osamu

    2005-01-01

    The binding kinetics of' 11 C-N-methyl piperidyl benzilate ( 11 C-NMPB) in rhesus monkey brain were studied using animal positron emission tomography (PET) (SHR2000). This study is intended to assess the validity of the method using the cerebellum as a reference region, and to evaluate the effects of anesthesia on 11 C -NMPB binding. Two monkeys, anesthetized with ketamine, received intravenous 11 C-NMPB alone (370-760 MBq, 11 C-NMPB accumulated densely in the striatum and cerebral cortex with time. In contrast, the tracer accumulation significantly decreased with increased doses of nonradioactive NMPB. In the cerebellum, on the other hand, the accumulation of 11 C-NMPB remained low and the tracer was slowly eliminated from the brain following the injection. 11 C-NMPB binding in the cerebellum was barely affected by the increased dose of nonradioactive NMPB. We thus concluded that the specific 11 C-NMPB binding was negligible in the cerebellum, and performed simplified evaluation of 11 C-NMPB binding in each brain region by a graphical method using the cerebellum as a reference region. PET was conducted 26 times, in total both in ketamine-anesthetized and awake monkeys (n=3 each). Measurements of 11 C-NMPB binding showed good run-to-run reproducibility within individual animals. When 11 C-NMPB binding was compared between ketamine-treated and awake animals, a significant increase in 11 C-NMPB binding was observed in the striatum but not in other brain regions of ketamine-treated animals. (author)

  15. μ3-Carbonato-κ3 O:O′:O′′-tris­{(η6-ben­zene)[(R)-1-(1-amino­ethyl)naphthyl-κ2 C 2,N]ruthenium(II)} hexa­fluorido­phosphate dichloro­methane solvate

    Science.gov (United States)

    Sortais, Jean-Baptiste; Brelot, Lydia; Pfeffer, Michel; Barloy, Laurent

    2008-01-01

    The title compound, [Ru3(C12H12N)3(CO3)(C6H6)3]PF6·CH2Cl2, was obtained unintentionally as the product of an attempted deprotonation of the monomeric parent ruthenium complex [Ru(C12H12N)(C6H6)(C2H3N)]PF6. The carbonate ligand bridges three half-sandwich cyclo­ruthenated fragments, each of them exhibiting a pseudo-tetra­hedral geometry. The configuration of the Ru atoms is S. The naphthyl groups of the enanti­opure cyclo­ruthenated benzylic amine ligands point in the same direction, adopting a propeller shape. PMID:21201869

  16. Synthesis of 'no-carrier-added' sup(11)C-labelled nitrosoureas

    International Nuclear Information System (INIS)

    Diksic, M.; Farrokhzad, S.; Yamamoto, Y.L.; Feindel, W.

    1985-01-01

    Syntheses for sup(11)C-labelled chemotherapeutic drugs CCNU, BFNU and CFNU (analogs of BCNU) as well as an improved synthesis for sup(11)C-BCNU are described. The procedures for the separation of dual isomers in the case of sup(11)C-labelled CCNU and CFNU are discussed. The specific activity of these 'no-carrier-added' radiopharmaceuticals was approximately 10sup(4) lower than expected for a carrier-free product. The syntheses were normally finished 20-25 min after the end of the collection of sup(11)C-COClsub(2). Chemical and radiochemical purity of the final products as determined by HPLC and TLRC, respectively, was at least 98%. The syntheses yielded 10-25 mCi of nitrosourea ready for use in PET studies. (author)

  17. Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takeshi [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Haradahira, Terushi [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan)], E-mail: terushi@niu.ac.jp; Fujimoto, Noriko [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Okauchi, Takashi; Maeda, Jun; Suzuki, Kazutoshi; Suhara, Tetsuya [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Yamamoto, Fumihiko; Sasaki, Shigeki; Mukai, Takahiro [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Yamaguchi, Hiroshi [Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Maeda, Minoru [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan)

    2008-02-15

    High-affinity iodine- and ethyl-C-5 substituted analogs of 4-hydroxy-3-(3-[{sup 11}C]methoxyphenyl)-2(1H)-quinolone ([{sup 11}C]4HQ) were synthesized as new positron emission tomography radioligands for the glycine-binding sites of the N-methyl-D-aspartate (NMDA) ion channel. Although both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[{sup 11}C]4HQ (5Et-[{sup 11}C]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site agonists and antagonists. In contrast, 5-iodo-[{sup 11}C]4HQ (5I-[{sup 11}C]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[{sup 11}C]4HQ and 5I-[{sup 11}C]4HQ was quite similar to that previously observed between [{sup 11}C]L-703,717 and [{sup 11}C]4HQ, both glycine-site antagonists. In vivo brain uptakes of these {sup 11}C-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes of 5Et- and 5I-[{sup 11}C]4HQ at 1 min after intravenous injections were comparable to that of [{sup 11}C]4HQ, but they were 1.3-2.1 times higher than that of [{sup 11}C]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [{sup 11}C]4HQ and 5Et-[{sup 11}C]4HQ in contrast to [{sup 11}C]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[{sup 11}C]4HQ (16-36% inhibition) but not that of 5I-[{sup 11}C]4HQ. In this study, it was found that a small structural change in [{sup 11}C]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding sites for [{sup 11}C]4-hydroxyquinolones on the NMDA ion channel

  18. Synthesis of electrophilic 11C-synthons: 11C-cyanogen bromide and some 11C-cyano reagents

    International Nuclear Information System (INIS)

    Westerberg, G.; Malmborg, P.; Langstroem, B.

    1990-01-01

    A fast, simple, and reliable method has been developed for the synthesis of carbon-11 labelled cyanogen bromide and several of its stabilized amine salts or cyanates. Preparation of cyanogen bromide is by bromination (bromine gas) of carbon-11 labelled hydrocyanic acid, followed by reaction with a tertiary amine or a phenol to yield the ammonium salts or cyanates

  19. 2,3-Diphenylmaleimide 1-methylpyrrolidin-2-one monosolvate

    Directory of Open Access Journals (Sweden)

    Evgeny Bulatov

    2014-03-01

    Full Text Available In the title compound, C16H11NO2·C5H9NO, the dihedral angles between the maleimide and phenyl rings are 34.7 (2 and 64.8 (2°. In the crystal, the 2,3-diphenylmaleimide and 1-methylpyrrolidin-2-one molecules form centrosymmetrical dimers via pairs of strong N—H...O hydrogen bonds and π–π stacking interactions between the two neighboring maleimide rings [centroid–centroid distance = 3.495 (2 Å]. The dimers are further linked by weak C—H...O and C—H...π hydrogen bonds into a three-dimensional framework.

  20. In vivo evaluation of [11C]-3-[2-[(3-methoxyphenylamino)carbonyl]ethenyl]-4,6-dichloroindole- 2-carboxylic acid ([11C]3MPICA) as a PET radiotracer for the glycine site of the NMDA ion channel

    International Nuclear Information System (INIS)

    Waterhouse, Rikki N.; Sultana, Abida; Laruelle, M.

    2002-01-01

    Alterations in normal NMDA receptor composition, densities and function have been implicated in the pathophysiology of certain neurological and neuropsychiatric disorders such as Parkinson's Disease, Huntington's Chorea, schizophrenia, alcoholism and stroke. In our first effort to provide PET ligands for the NMDA/glycine site, we reported the synthesis of a novel high affinity glycine site ligand, 3-[2-[(3-methoxyphenylamino)carbonyl]ethenyl]-4,6-dichloroindole-2 -carboxylic acid ((3MPICA), Ki=4.8±0.9 nM) and the corresponding carbon-11 labeled PET ligand, [ 11 C]3MPICA. We report here the in vivo evaluation of [ 11 C]3MPICA in rats. Biodistribution analysis revealed that [ 11 C]3MPICA exhibited low degree of brain penetration and high blood concentration. The average uptake at two minutes was highest in the cerebellum (0.19±0.04 %ID/g) and thalamus (0.18±0.05 %ID/g) and lower in the hippocampus (0.13±0.03) and frontal cortex (0.11±0.04 %ID/g). The radioactivity cleared quickly from all brain regions examined. Administration of unlabeled 3MPICA (1 mg/kg, i.v.) revealed at 60 minutes a small general reduction in regional brain radioactivity concentrations in treated animals versus controls, however, the blood radioactivity concentration was also lowered, confounding the assessment of the degree of saturable binding. Warfarin co-administration (100 mg/kg, i.v.) significantly lowered blood activity at 5 minutes post-injection (-27%, P 11 C]3MPICA does not appear to be a promising PET radiotracer for in vivo use