WorldWideScience

Sample records for n-substituted aryl compounds

  1. Characterization and expression of hepatic sulfotransferase involved in the metabolism of N-substituted aryl compounds.

    Yamazoe, Y; Ozawa, S; Nagata, K.; Gong, D W; R. Kato

    1994-01-01

    An aryl sulfotransferase, whose cDNA was isolated from the rat liver library, was found to catalyze bioactivation of minoxidil through N-O-sulfation and N-sulfation of a carcinogenic heterocyclic amine, IQ, by expression in COS-1 cells. cDNA of a human ortholog also was isolated and characterized as a major minoxidil-activating enzyme in human liver. Another group of aryl sulfotransferases catalyzing O-sulfation of carcinogenic N-hydroxyarylamines was separated from livers of rats and humans....

  2. A selective palladium-catalyzed carbonylative arylation of aryl ketones to give vinylbenzoate compounds.

    Schranck, Johannes; Tlili, Anis; Neumann, Helfried; Alsabeh, Pamela G; Stradiotto, Mark; Beller, Matthias

    2012-12-01

    Preparation of enols: when treated with [{Pd(cinnamyl)Cl}(2)]/cataCXium A (nBuPAd(2), Ad=adamantyl) under an atmosphere of CO, aryl ketones react with aryl halides in a carbonylative C-O coupling reaction to form (Z)-vinyl benzoates. PMID:23143936

  3. Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

    Burkhard Koenig

    2011-01-01

    Full Text Available N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.

  4. Preparing poly(aryl ethers) using alkaline earth metal carbonates, organic acid salts, and optionally copper compounds, as catalysts

    This patent describes an improved process for preparing poly(aryl ethers) and poly(aryl ether ketones) by the reaction of a mixture of at least one bisphenol and at least one dihalobenzenoid compound, and/or a halophenol. The improvement comprises providing to the reaction, a base which is a combination of an alkaline earth metal carbonate and/or bicarbonate and a potassium, rubidium, or cesium salt of an organic acid or combination of organic salts thereof

  5. Preparing poly(aryl ethers) using alkaline earth metal carbonates, organic acid salts, and optionally copper compounds, as catalysts

    Winslow, P.A.; Kelsey, D.R.; Matzner, M.

    1988-09-27

    This patent describes an improved process for preparing poly(aryl ethers) and poly(aryl ether ketones) by the reaction of a mixture of at least one bisphenol and at least one dihalobenzenoid compound, and/or a halophenol. The improvement comprises providing to the reaction, a base which is a combination of an alkaline earth metal carbonate and/or bicarbonate and a potassium, rubidium, or cesium salt of an organic acid or combination of organic salts thereof.

  6. Microwave-assisted synthesis and evaluation of antibacterial activity of 2,2'-(naph- thalene-2,7-diylbis(oxy))bis(N'-substituted acetohydrazide) derivatives

    A. Sivakumar; Satyanarayana, V. S. V.; K. Venkatesan

    2012-01-01

    A series of Schiff base of 2,2'-(naphthalene-2,7-diylbis(oxy))bis(N'-substituted acetohydrazide) (4a-m) derivatives has been synthesized by the acid catalyzed condensation of aryl/hetero aromatic aldehydes with 2,2'-(naphthalene-2,7-diylbis(oxy))diacetohydrazide (3) under microwave irradiation and conventional method for comparison. The structures of all the newly synthesized compounds have been characterized by IR, 1H NMR, 13C NMR and Mass spectra. All the synthesized compounds have been scr...

  7. Study using 1 H and 13 V NMR of 3-aryl-s-triazole benzoate azole type compounds and intermediaries

    Approximately 62% of the compounds used for medical purposes are heterocyclic, and are distributed as follows: 95% containing hydrogen, 28% containing sulfur and 18% containing oxygen in the structural composition. Some triazole-s-triazole type hetero aromatic systems and intermediaries, such as 1-aryl hydrazides exhibited bactericide, anti inflammatory and fungi stat activities. All the triazoles are are obtained synthetically, and are not found in the Nature. The proton and carbon-13 spectra of the non usual I, II and III compounds that we obtained are discussed in this work

  8. Palladium-catalysed cross-coupling reaction of ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds with aryl bromides: A direct protocol for the preparation of unsymmetrical biaryls

    Siphamandla Sithebe

    2014-05-01

    Full Text Available There has been a significant interest in organoboron compounds such as arylboronic acids, arylboronate esters and potassium aryltrifluoroborate salts because they are versatile coupling partners in metal-catalysed cross-coupling reactions. On the other hand, their nitrogen analogues, namely, 1,3,2-benzodiazaborole-type compounds have been studied extensively for their intriguing absorption and fluorescence characteristics. Here we describe the first palladium-catalysed Suzuki–Miyaura cross-coupling reaction of easily accessible and ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole derivatives with various aryl bromides. Aryl bromides bearing electron-withdrawing, electron-neutral and electron-donating substituents are reacted under the catalytic system furnishing unsymmetrical biaryl products in isolated yields of up to 96% in only 10 minutes.

  9. Direct Synthesis of 5-Aryl Barbituric Acids by Rhodium(II)-Catalyzed Reactions of Arenes with Diazo Compounds**

    Best, Daniel; Burns, David J.; Lam, Hon Wai

    2015-01-01

    A commercially available rhodium(II) complex catalyzes the direct arylation of 5-diazobarbituric acids with arenes, allowing straightforward access to 5-aryl barbituric acids. Free N—H groups are tolerated on the barbituric acid, with no complications arising from N—H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor.

  10. Direct Synthesis of 5-Aryl Barbituric Acids by Rhodium(II)-Catalyzed Reactions of Arenes with Diazo Compounds**

    Best, Daniel; Burns, David J; Lam, Hon Wai

    2015-01-01

    A commercially available rhodium(II) complex catalyzes the direct arylation of 5-diazobarbituric acids with arenes, allowing straightforward access to 5-aryl barbituric acids. Free N—H groups are tolerated on the barbituric acid, with no complications arising from N—H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor. PMID:25959544

  11. Direct Synthesis of 5-Aryl Barbituric Acids by Rhodium(II)-Catalyzed Reactions of Arenes with Diazo Compounds.

    Best, Daniel; Burns, David J; Lam, Hon Wai

    2015-06-15

    A commercially available rhodium(II) complex catalyzes the direct arylation of 5-diazobarbituric acids with arenes, allowing straightforward access to 5-aryl barbituric acids. Free N-H groups are tolerated on the barbituric acid, with no complications arising from N-H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor. PMID:25959544

  12. Novel Fluorinated PhosphorusSulfur Heteroatom Compounds: Synthesis and Characterization of Ferrocenyl- and Aryl-Phosphonofluorodithioic Salts, Adducts, and Esters

    Guoxiong Hua

    2015-07-01

    Full Text Available A series of novel ferrocenyl- and aryl-phosphonofluorodithioic salts, adducts, and esters has been prepared. The reaction of 2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide {[FcP(?-SS]2, FcLR} with dry KF or tetrabutylammonium fluoride (TBAF led to the corresponding potassium and tetrabutylammonium salts of ferrocenyldithiofluorophosphinic acids. Treating potassium ferrocenyldithiofluorophosphinic acid with an equimolar amount of tetraphenylphosphonium chloride readily yielded the corresponding organic adducts, and with mono- and di-halogenated alkanes generated a series of the corresponding esters of ferrocenylphosphonofluoridodithioates. Similarly, using 1,3-epithionaphtho[1,8-cd][1,2,6] oxadiphosphinine 1,3-disulfide or Belleaus Reagent in place of FcLR resulted in the corresponding novel salts, adducts, and ester derivatives. All new compounds have been characterized by means of multi-NMR (1H, 13C, 31P, 19F spectroscopy and accurate mass measurement in conjunction with single crystal X-ray crystallography of four structures.

  13. Synthesis and luminescent properties of 4′-phenyl-2,2′:6′,2″-terpyridyl compounds bearing different aryl substituents

    Liu, Yujian; Guo, Jun [Department of Applied Chemistry, College of Sciences, Nanjing Tech University, Nanjing 210009 (China); Liu, Rui, E-mail: rui.liu@njtech.edu.cn [Department of Applied Chemistry, College of Sciences, Nanjing Tech University, Nanjing 210009 (China); Wang, Qiang; Jin, Xiaodong; Ma, Liangwei; Lv, Wangjie [Department of Applied Chemistry, College of Sciences, Nanjing Tech University, Nanjing 210009 (China); Liu, Shishen; Yuan, Shidong [Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083 (China); Zhu, Hongjun, E-mail: zhuhj@njtech.edu.cn [Department of Applied Chemistry, College of Sciences, Nanjing Tech University, Nanjing 210009 (China)

    2015-01-15

    A series of new 4′-phenyl-2,2′:6′,2″-terpyridine compounds bearing different aryl substituents (Ar=phenyl (1a), 2,4-difluorophenyl (1b), 4-(trifluoromethyl) phenyl (1c), 4-methoxyphenyl (1d), 9-hexyl-9H-carbazolyl (1e), 9,9-dihexyl-9H-fluorenyl (1f), 4-(diphenylamino)phenyl (1g)) were synthesized and characterized. The influence of the aryl substituents on the luminescence of these compounds is systematically investigated by spectroscopic methods and simulated by density functional theory (DFT) calculations. All compounds exhibit structured absorption bands in the UV region; and broad, structureless charge-transfer bands/shoulders for 1d–1g, which systematically red-shifts when electron-donating substituents are introduced to the phenyl rings, but blue-shifts when electron-withdrawing substituents are attached on the phenyl rings. All compounds are emissive in solution at room temperature (λ (table) =358–489 nm, Φ{sub F}=0.16–0.92, τ{sub F}=0.77–2.24 ns), which can be attributed to {sup 1}π, π*/{sup 1}ICT (intramolecular charge transfer) state. Their fluorescent quantum yields increases when the electron-donating aryl substituents attached on the phenyl rings. DFT calculations on 1a–1g were also performed to gain insight into the nature of the ground electronic state. As the representative of compounds with electron-donating substituents, 1f exhibited high fluorescent quantum yields (Φ{sub f}≥0.90 in solvents) while the compounds with electron-withdrawing substituents showed relative low fluorescent quantum yields. Their photophysical properties have been investigated with the aim to provide a basis for elucidating the structure-property correlations and developing new blue light-emitting materials. - Highlights: • A series of 4′-phenyl-2,2′:6′,2″-terpyridine derivatives terminally capped with different aryl substituents. • Photophysical properties of these D-π-A or A-π-A type compounds were systematically investigated via spectroscopic, theoretical and electrochemical methods. • The relatively high fluorescence quantum yields make these compounds as potential candidates of blue light-emitting materials.

  14. Quantitative High-Throughput Screening and Confirmation Studies for Identification of Compounds that Activate the Aryl Hydrocarbon Receptor Pathway (SETAC)

    The aryl hydrocarbon receptor (AhR) is a transcription factor that mediates adaptive responses to known environmental pollutants, such as aromatic hydrocarbons, through regulation of Phase I and II xenobiotic metabolizing enzymes as well as important growth and differentiation pa...

  15. SYNTHESIS OF BIOLOGICALLY ACTIVE 2-CHLORO-N-ALKYL/ARYL ACETAMIDE DERIVATIVES

    S.A.Katke

    2011-07-01

    Full Text Available Medicinal chemistry plays an important role in development of drug for cure; maintain and improved health of human being. It is also equally important to design chemical entities for prevent the growth of micro-organism, which come in contact with human being in day-to-day life. We have synthesized 2-chloro-N-alkyl/aryl Acetamide derivatives with an aim as new bioactive agent, which can be used as anti microbial agents such as herbicides, antifungal, disinfectant. The present study involves the synthesis, purification and characterization of various N-substituted chloroacetamide derivatives. The chloroacetyl chloride treated with various aliphatic and aromatic amines at room temperature with stirring for few hours with monitoring reaction by thin layer chromatography gave 2-chloro-N-alkyl/aryl Acetamide as solid compounds. We checked the melting point of synthesized compounds with an open ended capillary tube method. The spectral techniques like Infra red and GC-MS have been used for characterization and establishment of structure of synthesized compounds. The antimicrobial screening of the synthesized chloroacetamides have shown excellent antibacterial and antifungalactivity.

  16. Lewis acid free high speed synthesis of nimesulide-based novel N-substituted cyclic imides

    The first synthesis of nimesulide-based novel cyclic imides has been accomplished via the reaction of an amine prepared from nimesulide with appropriate anhydrides in the presence of sodium acetate. Using this process a variety of N-substituted cyclic imides was prepared in good yields in glacial acetic acid. Some of the compounds synthesized showed anti-inflammatory activities when tested in vivo. (author)

  17. Lewis acid free high speed synthesis of nimesulide-based novel N-substituted cyclic imides

    Kankanala, Kavitha; Mukkanti, Khagga [JNT University Hyderabad, Kukatpally (India); Pal, Sarbani, E-mail: sarbani277@yahoo.co [MNR Degree and PG College, Kukatpally, Hyderabad (India). Dept. of Chemistry; Reddy, Vangala Ranga [Dr. Reddy' s Laboratories Ltd. Integrated Product Development, Bachupally, Hyderabad (India)

    2010-07-01

    The first synthesis of nimesulide-based novel cyclic imides has been accomplished via the reaction of an amine prepared from nimesulide with appropriate anhydrides in the presence of sodium acetate. Using this process a variety of N-substituted cyclic imides was prepared in good yields in glacial acetic acid. Some of the compounds synthesized showed anti-inflammatory activities when tested in vivo. (author)

  18. Palladium-Catalyzed Carbonylation of Aryl Bromides with N-Substituted Cyanamides

    Lian, Zhong; Friis, Stig D.; Lindhardt, Anders T.; Skrydstrup, Troels

    2014-01-01

    reaction time of only five hours leading to the corresponding N-alkyl cyanamides in good yields. The methodology was further extended to 13C isotope labeling of the carbonyl group through the use of a 13CO produced from the corresponding 13C-labeled version of the silacarboxylic acid....

  19. Prostaglandin hydroperoxidase-catalyzed activation of certain N-substituted aryl renal and bladder carcinogens

    Zenser, T. V.; Cohen, S. M.; Mattammal, M. B.; Wise, R. W.; Rapp, N. S.; Davis, B. B.

    1983-01-01

    Certain carcinogens are thought to induce renal and bladder cancer following metabolic activation. We propose a model system for this activation and provide supporting experimental evidence. This model proposes that renal and bladder carcinogens' entry into the urinary tract is facilitated, that carcinogens are activated by the prostaglandin hydroperoxidase activity of prostaglandin endoperoxide synthetase (PES), and that activation results in covalent binding to nucleic acids which can initi...

  20. Synthesis and cytotoxic activity of N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal.

    Joselice e Silva, M; Alves, A J; Do Nascimento, S C

    1998-03-01

    Five new N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal were synthesized. Safrole, a natural product obtained from sassafras oil (Ocotea pretiosa), was oxidized to alcohol using BH3-THF and H2O2, followed by oxidation to aldehyde using pyridinium dichromate (PDC) and condensation with five N-substituted derivatives of thiosemicarbazide. Tests were performed to evaluate the cytotoxic activity with continuous chain KB cells (epidermoide carcinoma of the floor of the mouth). Compounds 5 and 6 showed IC50 values of 1.5 and 4.6 micrograms/ml, respectively. PMID:9639871

  1. Activity of Antifungal Organobismuth(III Compounds Derived from Alkyl Aryl Ketones against S. cerevisiae: Comparison with a Heterocyclic Bismuth Scaffold Consisting of a Diphenyl Sulfone

    Toshihiro Murafuji

    2014-07-01

    Full Text Available A series of hypervalent organobismuth(III compounds derived from alkyl aryl ketones [XBi(5-R'C6H3-2-COR(Ar] was synthesized to investigate the effect of the compounds’ structural features on their antifungal activity against the yeast Saccharomyces cerevisiae. In contrast to bismuth heterocycles [XBi(5-RC6H3-2-SO2C6H4-1'-] derived from diphenyl sulfones, a systematic quantitative structure-activity relationship study was possible. The activity depended on the Ar group and increased for heavier X atoms, whereas lengthening the alkyl chain (R or introducing a substituent (R' reduced the activity. IBi(C6H4-2-COCH3(4-FC6H4 was the most active. Its activity was superior to that of the related acyclic analogues ClBi[C6H4-2-CH2N(CH32](Ar and ClBi(C6H4-2-SO2 tert-Bu(Ar and also comparable to that of heterocyclic ClBi(C6H4-2-SO2C6H4-1'-, which was the most active compound in our previous studies. Density function theory calculations suggested that hypervalent bismuthanes undergo nucleophilic addition with a biomolecule at the bismuth atom to give an intermediate ate complex. For higher antifungal activity, adjusting the lipophilicity-hydrophilicity balance, modeling the three-dimensional molecular structure around the bismuth atom, and stabilizing the ate complex appear to be more important than tuning the Lewis acidity at the bismuth atom.

  2. Synthesis, Characterization and Antimicrobial Activity of 2-hydroxy-5-bromo-4- methoxy-N-(substituted phenyl) chalconeimine

    Patil S; Utale P; Gholse S; Pande S; Thakur S.

    2013-01-01

    A series of 2-hydroxy-5-bromo-4-methoxy-N-(substituted phenyl) chalconeimine was synthesized,characterized and tested for their antimicrobial activity. These new derivative was achieved by treating2-hydroxy-5-bromo-4-methoxy chalcone with substituted aniline at reflux temperature using ethanol assolvent in presence of H2SO4. Structures of the synthesized compounds were characterized using IR, 1HNMRand mass spectroscopy. The synthesized compounds were screened for their in vitro antibacteriala...

  3. Synthesis, characterization and dynamic NMR studies of a novel chalcone based N-substituted morpholine derivative

    Baskar, R.; Baby, C.; Moni, M. S.; Subramanian, K.

    2013-05-01

    The synthesis of a novel chalcone based N-substituted morpholine derivative namely, (E)-1-(biphenyl-4-yl)-3-(4-(5-morpholinopentyloxy) phenyl) prop-2-en-1-one (BMPP), using a two step protocol is reported. The compound is characterized by FTIR, GC-MS and FTNMR spectroscopy techniques. Advanced 2D NMR techniques such as gradient enhanced COSY, HSQC, HMBC and NOESY were employed to establish through-bond and through-space correlations. Dynamic NMR measurements were carried out to obtain the energy barrier to ring inversion of the morpholine moiety.

  4. Modern Arylation Methods

    Ackermann, Lutz

    2009-01-01

    Today, arylation methods are belonging to the most important reaction types in organic synthesis. Lutz Ackermann, a young and ambitious professor has gathered a number of top international authors to present the first comprehensive book on the topic. Starting from a historical review, the book covers hot topics like Palladium-catalyzed arylation of N-H and alpha-C-H-acidic Bonds, Copper-catalyzed arylation of N-H and O-H Bonds, direct arylation reactions, carbanion aromatic synthesis, arylation reactions of alkenes, alkynes and much more. This compact source of high quality information is indi

  5. Synthesis and antitumor activity of novel N-substituted carbazole imidazolium salt derivatives

    Liu, Lan-Xiang; Wang, Xue-Quan; Zhou, Bei; Yang, Li-Juan; Li, Yan; Zhang, Hong-Bin; Yang, Xiao-Dong

    2015-01-01

    A series of novel N-substituted carbazole imidazolium salt derivatives has been prepared and investigated for their cytotoxic activity against five human tumor cell lines by MTS assay. The results indicated that the existence of 5,6-dimethyl-benzimidazole ring, substitution of the imidazolyl-3-position with a 2-bromobenzyl or naphthylacyl group, as well as alkyl chain length between carbazole and imidazole ring were important for the antitumor activity. Compound 61, bearing a 2-bromobenzyl substituent at position-3 of the 5,6-dimethyl-benzimidazole, showed powerful inhibitory activities and was more selective to HL-60, SMMC-7721, MCF-7 and SW480 cell lines with IC50 values 0.512.48??M. Mechanism of action studies revealed that this new compound could remarkably induce cell cycle arrest and apoptosis in SMMC-7721 cells. This work provides alternative novel way for future drug development based on carbazole and imidazolium salt scaffolds. PMID:26287982

  6. Synthesis, Characterization and Antimicrobial Activity of 2-hydroxy-5-bromo-4- methoxy-N-(substituted phenyl chalconeimine

    Patil S

    2013-05-01

    Full Text Available A series of 2-hydroxy-5-bromo-4-methoxy-N-(substituted phenyl chalconeimine was synthesized,characterized and tested for their antimicrobial activity. These new derivative was achieved by treating2-hydroxy-5-bromo-4-methoxy chalcone with substituted aniline at reflux temperature using ethanol assolvent in presence of H2SO4. Structures of the synthesized compounds were characterized using IR, 1HNMRand mass spectroscopy. The synthesized compounds were screened for their in vitro antibacterialactivity against bacteria S. aureus, E. coli, P. aeruginosa and S. Pyogenes. And antifungal activityagainst C. Albicans and A.Clavatus some of these compounds exhibited moderate to good activity.

  7. Evidence of N substitution by Mn in GaN

    Pereira, LMC; Decoster, S; Correia, JG; da Silva, MR; Vantomme, A; Araújo, JP

    2012-01-01

    We report on the lattice location of Mn in wurtzite GaN using beta− emission channeling. In addition to the majority substituting for Ga, we locate up to 20% of the Mn atoms in N sites. We propose that the incorporation of Mn in N sites is enabled under sufficiently high concentrations of N vacancies, and stabilized by a highly charged state of the Mn cations. Since N substitution by Mn impurities in wurtzite GaN has never been observed experimentally or even considered theoretically before, it challenges the current paradigm of transition metal incorporation in wide-gap dilute magnetic semiconductors.

  8. Novel multicomponent synthesis of 2,9-dihydro-9-methyl-2-oxo-4-aryl- 1-pyrido[2,3-]indole-3-carbonitrile compounds

    Saman Damavandi; Reza Sandaroos

    2013-01-01

    Novel multicomponent approach for the synthesis of 2,9-dihydro-2-oxo-4-aryl-1-pyrido[2,3-]indole-3-carbonitrile derivatives via one-pot cyclocondensation reaction of substituted (triethoxymethyl) arene, 1-methyl-1-indol-2-ol and cyanoacetamide in the presence of silica supported ionic liquid [pmim]HSO4SiO2 (silica-supported 1-methyl-3-(triethoxysilylpropyl)imidazolium hydrogensulphate) has been reported.

  9. Concise synthesis of dihydrochalcones via palladium-catalyzed coupling of aryl halides and 1-aryl-2-propen-1-ols.

    Briot, Anne; Baehr, Corinne; Brouillard, Raymond; Wagner, Alain; Mioskowski, Charles

    2004-02-20

    An expedient route to substituted dihydrochalcones is reported. The key step is a palladium-assisted arylation of 1-aryl-2-propen-1-ols. This two-step/one-purification process allows the synthesis of a wide range of compounds with original substitution patterns, including polyphenolic derivatives. PMID:14961696

  10. Lipase-Catalyzed Kinetic Resolution of Novel Antifungal N-Substituted Benzimidazole Derivatives.

    Łukowska-Chojnacka, Edyta; Staniszewska, Monika; Bondaryk, Małgorzata; Maurin, Jan K; Bretner, Maria

    2016-04-01

    A series of new N-substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase-catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100). Chirality 28:347-354, 2016. © 2016 Wiley Periodicals, Inc. PMID:26922853

  11. Synthesis of nanodispersible 6-aryl-2,4-diamino-1,3,5-triazine and its derivatives

    A series of novel branched derivatives of 6-aryl-2,4-diamino-1,3,5-triazine from corresponding aryl nitriles and dicyanodiamide was synthesized. These compounds show a nanodispersibility and good thermal stability.

  12. Synthesis, antiviral and cytotoxicity studies of novel N-substituted indophenazine derivatives

    P Selvam

    2012-01-01

    Full Text Available A series of novel N-substituted indophenazine derivatives were synthesised and screened for antiviral activity against a panel of human pathogenic viruses. New compounds were synthesised through modifying the N-hydrogen of indophenazine moiety with different substitution and formaldehyde by Mannich reaction. The structure of the synthetic compounds was characterised by means of infra red and nuclear magnetic resonance spectral data. The compound 10H-indolo-2-Amino pyridine [3,2-b] quinoxalines inhibits Herpes simplex virus-1 and vaccinia virus at a concentration of 12 μg/ml, and the cytotoxicy was found to be 100 μg/ml. 4-Aminobenzene sulfonamide-10H-indolo [3,2-b] quinoxalines inhibit vaccinia virus at a concentration of 12 μg/ml and cytotoxicy was found to be 100 μg/ml. The anti-HIV activities of the new compounds were also screened for in vitro antiviral activity against replication of HIV-1 (IIIB and HIV-2 (ROD in MT-4 cells using zidovudine (AZT as standard. Pthalimide derivative inhibited the replication of HIV-2 (EC 50 =11.60 μg/ml and CC 50 =61.63 μg/ml in MT-4 cells.

  13. N-substituted 2-isonicotinoylhydrazinecarboxamides--new antimycobacterial active molecules.

    Rychtar?kov, Zuzana; Krtk, Martin; Gazvoda, Martin; Komlov, Markta; Polanc, Slovenko; Ko?evar, Marijan; Stola?kov, Ji?ina; Vinov, Jarmila

    2014-01-01

    This report presents a new modification of the isoniazid (INH) structure linked with different anilines via a carbonyl group obtained by two synthetic procedures and with N-substituted 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-amines prepared by their cyclisation. All synthesised derivatives were characterised by IR, NMR, MS and elemental analyses and were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80 and one clinical isolated strain of M. kansasii 6509/96. 2-Isonicotinoyl-N-(4-octylphenyl)hydrazinecarboxamide displayed an in vitro efficacy comparable to that of INH for M. tuberculosis with minimum inhibitory concentrations (MICs) of 1-2 ?M. Among the halogenated derivatives, the best anti-tuberculosis activity was found for 2-isonicotinoyl-N-(2,4,6-trichlorophenyl)hydrazinecarboxamide (MIC=4 ?M). In silico modelling on the enoyl-acyl carrier protein reductase InhA confirmed that longer alkyl substituents are advantageous for the interactions and affinity to InhA. Most of the hydrazinecarboxamides, especially those derived from 4-alkylanilines, exhibited significant activity against INH-resistant nontuberculous mycobacteria. PMID:24686575

  14. N-Substituted 2-Isonicotinoylhydrazinecarboxamides New Antimycobacterial Active Molecules

    Zuzana Rychtar?kov

    2014-03-01

    Full Text Available This report presents a new modification of the isoniazid (INH structure linked with different anilines via a carbonyl group obtained by two synthetic procedures and with N-substituted 5-(pyridine-4-yl-1,3,4-oxadiazole-2-amines prepared by their cyclisation. All synthesised derivatives were characterised by IR, NMR, MS and elemental analyses and were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80 and one clinical isolated strain of M. kansasii 6509/96. 2-Isonicotinoyl-N-(4-octylphenylhydrazinecarboxamide displayed an in vitro efficacy comparable to that of INH for M. tuberculosis with minimum inhibitory concentrations (MICs of 12 ?M. Among the halogenated derivatives, the best anti-tuberculosis activity was found for 2-isonicotinoyl-N-(2,4,6-trichlorophenylhydrazinecarboxamide (MIC = 4 ?M. In silico modelling on the enoyl-acyl carrier protein reductase InhA confirmed that longer alkyl substituents are advantageous for the interactions and affinity to InhA. Most of the hydrazinecarboxamides, especially those derived from 4-alkylanilines, exhibited significant activity against INH-resistant nontuberculous mycobacteria.

  15. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    2010-07-01

    ... acetamide (generic name). 721.225 Section 721.225 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a...-methyl-N-substituted acetamide (PMN P-84-393) is subject to reporting under this section for...

  16. Highly nonplanar, electron deficient, N-substituted tetra-oxocyclohexadienylidene porphyrinogens: structural, computational, and electrochemical investigations.

    Hill, Jonathan P; Hewitt, Ian J; Anson, Christopher E; Powell, Annie K; McCarty, Amy Lea; Karr, Paul A; Zandler, Melvin E; D'Souza, Francis

    2004-09-01

    The structures and electrochemistry of N-benzylated meso-tetrakis (3,5-di-tert-butyl-4-oxo-cyclohexa-2,5-dienylidene) porphyrinogens have been investigated. Structural determinations reveal the isomeric identity of the products obtained from the N-alkylation of the parent meso-tetra (oxo-cyclohexadienylidene) porphyrinogen. The compounds are subject to increased macrocyclic deformations upon increasing N-substitution culminating in the tetra-N-benzyl derivative, which has a buckling superimposed on the already highly puckered macrocycle. The electrochemical analyses emphasize the electron deficiency of the N-benzylated meso-tetra(oxo-cyclohexadienylidene) porphyrinogens and indicate that they can be considered as quinones conjugated via the unsaturated tetrapyrrolic macrocycle. The N-benzylated compounds studied form stable and well-defined pi-cation radical and pi-anion radical species because of their highly conjugated nature. Ab initio molecular orbital calculations at the B3LYP/3-21G() level confirmed the high degree of conjugation between tetrapyrrole and meso substituents and also gave good agreement between calculated and experimentally determined HOMO-LUMO band gap energies. PMID:15373471

  17. Synthesis and analgesic properties of N-substituted trans-4a-aryldecahydroisoquinolines.

    Zimmerman, D M; Cantrell, B E; Swartzendruber, J K; Jones, N D; Mendelsohn, L G; Leander, J D; Nickander, R C

    1988-03-01

    A representative series of N-substituted derivatives of the morphine-based trans-4a-aryldecahydroisoquinoline were synthesized and evaluated for opioid analgesic activities. Compounds with potent analgesic activity and high affinities for the mu and kappa opioid receptors were discovered. The effect of varying the N-substituent in the trans-4a-aryldecahydroisoquinoline paralleled, to a certain extent, previous findings with other morphine part structures. Replacement of the N-methyl with a phenethyl group significantly increased analgesic potency. The N-cyclopropylmethyl analogue was found in rodents to have mixed agonist-antagonist properties; however, its antagonist activity was far weaker than those reported for the N-(cyclopropylmethyl)morphinan and -benzomorphan derivatives. Resolution of the stereoisomers and determination of their absolute configuration by X-ray crystallography showed that the opioid receptor effects were predominantly found with the 4aR,8aR isomer, the same relative absolute configuration of morphine. Unexpectedly, the 4aR,8aR N-cyclopropylmethyl analogue (compound 30), which in rodents had mixed agonist-antagonist properties similar to those of pentazocine, was found in rhesus monkeys to behave as a full morphine-like agonist. PMID:2831363

  18. Practical Catalytic Asymmetric Synthesis of Diaryl-, Aryl Heteroaryl- and Diheteroarylmethanols

    Salvi, Luca; Kim, Jeung Gon; Walsh, Patrick J.

    2009-01-01

    Enantioenriched diaryl-, aryl heteroaryl- and diheteroarylmethanols exhibit important biological and medicinal properties. One-pot catalytic asymmetric syntheses of these compounds beginning from readily available aryl bromides are introduced. Thus, lithium-bromide exchange with commercially available aryl bromides and n-BuLi was followed by salt metathesis with ZnCl2 to generate ArZnCl. A second equivalent of n-BuLi was added to form the mixed organozinc, ArZnBu. In the presence of enantioen...

  19. Novel N-substituted aminobenzamide scaffold derivatives targeting the dipeptidyl peptidase-IV enzyme

    Al-Balas QA

    2014-01-01

    Full Text Available Qosay A Al-Balas,1 Munia F Sowaileh,1 Mohammad A Hassan,1 Amjad M Qandil,1,2 Karem H Alzoubi,3 Nizar M Mhaidat,3 Ammar M Almaaytah,4 Omar F Khabour51Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Pharmaceutical Sciences Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 5Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, JordanBackground: The dipeptidyl peptidase-IV (DPP-IV enzyme is considered a pivotal target for controlling normal blood sugar levels in the body. Incretins secreted in response to ingestion of meals enhance insulin release to the blood, and DPP-IV inactivates these incretins within a short period and stops their action. Inhibition of this enzyme escalates the action of incretins and induces more insulin to achieve better glucose control in diabetic patients. Thus, inhibition of this enzyme will lead to better control of blood sugar levels.Methods: In this study, computer-aided drug design was used to help establish a novel N-substituted aminobenzamide scaffold as a potential inhibitor of DPP-IV. CDOCKER software available from Discovery Studio 3.5 was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the DPP-IV enzyme. The designed compounds were synthesized and tested against a DPP-IV enzyme kit provided by Enzo Life Sciences. The synthesized compounds were characterized using proton and carbon nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and determination of melting point.Results: Sixty-nine novel compounds having an N-aminobenzamide scaffold were prepared, with full characterization. Ten of these compounds showed more in vitro activity against DPP-IV than the reference compounds, with the most active compounds scoring 38% activity at 100 µM concentration.Conclusion: The N-aminobenzamide scaffold was shown in this study to be a valid scaffold for inhibiting the DPP-IV enzyme. Continuing work could unravel more active compounds possessing the same scaffold.Keywords: diabetes mellitus, dipeptidyl peptidase-IV, aminobenzamide derivatives, hypoglycemic activity, CDOCKER software

  20. Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-β-carbolines.

    Manda, Sudhakar; Khan, Shabana I; Jain, Surendra K; Mohammed, Shabber; Tekwani, Babu L; Khan, Ikhlas A; Vishwakarma, Ram A; Bharate, Sandip B

    2014-08-01

    A series of N-substituted tetrahydro-β-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of Leishmania donovani, the causative agent for visceral leishmaniasis. The thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with IC50 values of 12.7, 9.1 and 22.1 μM, respectively. Analogs 9b and 11h were also effective against axenic amastigotes with IC50 values of 62.8 and 87.6 μM, respectively. The antileishmanial activity of analogs was then tested in human macrophage cell line infected with L. donovani amastigotes and 2-naphthyl linked analog 11h was found to be effective with IC50 value of 28.3 μM. Several analogs also displayed antitrypanosomal activity against Trypanosoma brucei, the causative agent for human African trypanosomiasis. Compounds 11e, 11f and 11h were more effective than others with IC50 values of 1.0, 8.9 and 10.2 μM, respectively. All synthesized analogs were not cytotoxic towards mammalian cell lines including Vero (monkey kidney fibroblasts), HEPG2 (human hepatoma cells), LLC-PK1 (pig kidney epithelial cells) and THP-1 (human macrophages). PMID:24980054

  1. Polypeptoids from N -Substituted Glycine N -Carboxyanhydrides: Hydrophilic, Hydrophobic, and Amphiphilic Polymers with Poisson Distribution

    Fetsch, Corinna

    2011-09-13

    Preparation of defined and functional polymers has been one of the hottest topics in polymer science and drug delivery in the recent decade. Also, research on (bio)degradable polymers gains more and more interest, in particular at the interface of these two disciplines. However, in the majority of cases, combination of definition, functionality and degradability, is problematic. Here we present the preparation and characterization (MALDI-ToF MS, NMR, GPC) of nonionic hydrophilic, hydrophobic, and amphiphilic N-substituted polyglycines (polypeptoids), which are expected to be main-chain degradable and are able to disperse a hydrophobic model compound in aqueous media. Polymerization kinetics suggest that the polymerization is well controlled with strictly linear pseudo first-order kinetic plots to high monomer consumption. Moreover, molar mass distributions of products are Poisson-type and molar mass can be controlled by the monomer to initiator ratio. The presented polymer platform is nonionic, backbone degradable, and synthetically highly flexible and may therefore be valuable for a broad range of applications, in particular as a biomaterial. © 2011 American Chemical Society.

  2. Structural Requirements of N-Substituted Spiropiperidine Analogues as Agonists of Nociceptin/Orphanin FQ Receptor

    Ling Yang

    2011-12-01

    Full Text Available The nociceptin/orphanin FQ (NOP receptor is involved in a wide range of biological functions, including pain, anxiety, depression and drug abuse. Especially, its agonists have great potential to be developed into anxiolytics. In this work, both the ligand- and receptor-based three-dimensional quantitative structureactivity relationship (3D-QSAR studies were carried out using comparative molecular field analysis (CoMFA and comparative molecular similarity indices analysis (CoMSIA techniques on 103 N-substituted spiropiperidine analogues as NOP agonists. The resultant optimal ligand-based CoMSIA model exhibited Q2 of 0.501, R2ncv of 0.912 and its predictive ability was validated by using an independent test set of 26 compounds which gave R2pred value of 0.818. In addition, docking analysis and molecular dynamics simulation (MD were also applied to elucidate the probable binding modes of these agonists. Interpretation of the 3D contour maps, in the context of the topology of the active site of NOP, provided insight into the NOP-agonist interactions. The information obtained from this work can be used to accurately predict the binding affinity of related agonists and also facilitate the future rational design of novel agonists with improved activity.

  3. MDMA-like behavioral effects of N-substituted piperazines in the mouse

    Yarosh, H.L.; Katz, E.B.; Coop, A.; Fantegrossi, W. E.

    2007-01-01

    Few studies have characterized the subjective effects of N-substituted piperazines, but these drugs show potential for abuse in humans, and have often been associated with MDMA (“ecstasy”) in this regard. The aim of the present studies was to test the capacity of N-substituted piperazines to induce a head-twitch response, alter locomotor activity, and induce MDMA-like discriminative stimulus effects in mice. Various doses of l-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl) piperazine (TF...

  4. The Genetic Basis for Evolved Tolerance to Dioxin-Like Compounds in Wild Atlantic Killifish: More Than the Aryl Hydrocarbon Receptor

    Populations of Atlantic killifish (Fundulus heteroclitus) resident to some US urban estuaries have independently evolved extreme and inherited tolerance to toxic dioxin-like compounds (DLCs). To further understand the genetic basis for this trait, we densely genotyped families o...

  5. Solvent free preparation of N-substituted maleanilic acid

    H. Saedi

    2013-04-01

    Full Text Available Six N-maleanilic acids namely N-(4-carboxymaleanilic acid (CAMAA, N-(4-bromomaleanilic acid (BMAA, N-(4-hydroxymaleanilic acid (HMAA, N-(3-hydroxymaleanilic acid (mHMAA, N-(4-chloromaleanilic acid (CMAA and N-(4-methylmaleanilic acid (MMAA were prepared by solvent free reaction between maleic anhydride and a 4-carboxy, 4-bromo, 4-hydroxy, 3-hydroxy, 4-chloro and 4-methyl aniline derivatives in good to excellent yield. FT-IR, 1H-NMR and 13C-NMR spectra revealed the confirmation of these compounds in good agreement.DOI: http://dx.doi.org/10.4314/bcse.v27i1.15

  6. Modular approach to novel chiral aryl-ferrocenyl phosphines by Suzuki cross-coupling

    Jensen, Jakob Feldthusen; Søtofte, Inger; Sorensen, H.O.; Johannsen, Mogens

    2002-01-01

    Two novel planar chiral and atropisomeric P,N and P,O aryl-ferrocenyl ligand systems have been developed. The strategy is short and involves a new synthetic approach to aryl-ferrocenyl compounds via a Suzuki cross-coupling procedure. The modular design can easily give access to variety of chiral...

  7. C-Arylation reactions catalyzed by CuO-nanoparticles under ligand free conditions

    Mazaahir Kidwai

    2010-04-01

    Full Text Available CuO-nanoparticles were found to be an excellent heterogeneous catalyst for C-arylation of active methylene compounds using various aryl halides. The products were obtained in good to excellent yield. The catalyst can be recovered and reused for four cycles with almost no loss in activity.

  8. Synthesis and Screening of Some New N-Substituted Derivatives of N-(4-Methylpyridin-2-ylbenzenesulfonamides as Potential Antibacterial Agents

    Aziz-ur-Rehman

    2014-03-01

    Full Text Available The two step synthesis of a series of N-substituted derivatives of N-(4-Methylpyridin-2-ylbenzenesulfonamide with potential antibacterial activity, has been reported. First step includes the synthesis of N-(4-Methylpyridin-2-ylbenzenesulfonamide (3 by reaction of 2-Amino-4-methylpyridine (1 and Benzenesulfonyl chloride (2 in a slightly basic aqueous medium. The molecule 3 was converted to N-Alkyl/aralkyl-N-(4-methylpyridin-2-ylbenzenesulfonamide derivatives, 5a-f, on treatment with alkyl/aralkyl halides, 4a-f, using lithium hydride as activator in N,N-dimethylformamide. The synthesized molecules were well corroborated by 1H-NMR, IR and EI-MS spectral data and evaluated for antibacterial activity against four gram-negative and two gram-positive bacteria. The evaluation results rendered these compounds as moderately good inhibitors and may be employed as therapeutic agent for certain inflammatory ailments.

  9. Synthesis of non-purine analogs of 6-aryl-9-benzylpurines, and their antimycobacterial activities. Compounds modified in the imidazole ring.

    Khoje, Abhijit Datta; Kulendrn, Aisvareya; Charnock, Colin; Wan, Baojie; Franzblau, Scott; Gundersen, Lise-Lotte

    2010-10-15

    Purine analogs modified in the five-membered ring have been synthesized and examined for antibacterial activity against Mycobacterium tuberculosis H(37)Rv in vitro employing the microplate alamar blue assay (MABA). The 9-deaza analogs were only found to be weak inhibitors, but the 8-aza-, 7-deaza- and 8-aza-7-deazapurine analogs studied displayed excellent antimycobacterial activities, some even substantially better than the parent purine. In the 7-deazapurine series, MIC values between 0.08 and 0.35 ?M, values comparable or better than the reference drugs used in the study (MIC rifampicin 0.09 ?M, MIC isoniazid 0.28 ?M and MIC PA-824 0.44 ?M). The five most active compounds were also examined against a panel of drug-resistant Mtb strain, and they all retained their activity. The compounds examined were significantly less active against M. tuberculosis in a state of non-replicating persistence (NRP). MIC in the low-oxygen-recovery assay (LORA) ? 60 ?M. The 7-deazapurines were somewhat more toxic towards mammalian cells, but still the selectivity indexes were excellent. The non-purine analogs exhibit a selective antimycobacterial activity. They were essentially inactive against Staphylococcus aureus and Escherichia coli. PMID:20833056

  10. Efficient synthesis of ?-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp2H bond arylations

    Fatiha Abdelmalek

    2015-10-01

    Full Text Available We report herein a two or three step synthesis of fluorinated ?-conjugated oligomers through iterative CH bond arylations. Palladium-catalyzed desulfitative arylation of heteroarenes allowed in a first step the synthesis of fluoroaryl-heteroarene units in high yields. Then, the next steps involve direct arylation with aryl bromides catalyzed by PdCl(C3H5(dppb to afford triad or tetrad heteroaromatic compounds via regioselective activation of C(sp2H bonds.

  11. Direct N9-arylation of purines with aryl halides

    Larsen, Anders Foller; Ulven, Trond

    2014-01-01

    An efficient method for N-arylation of purines is reported. The N-arylation is catalysed by Cu(i) and 4,7-bis(2-hydroxyethylamino)-1,10-phenanthroline (BHPhen) in aqueous DMF or ethanol. The reaction generally proceeds with high selectivity for the N(9)-position....

  12. Synthesis of N-substituted 6-trifluoromethyl-1,3-oxazinanes

    This work reports the synthesis of two new series of N-substituted 6-trifluoromethyl-1,3-oxazinanes and N-substituted 6-trifluoromethyl-1,3-oxazinan-2-ones from the cyclization of 4-ylamino-1,1,1-trifluoro-butan-2-ols with formaldehyde and triphosgene, respectively. The 4-ylamino-1,1,1-trifluoro-butan-2-ols were obtained in good yields from the reduction of the parent 4-ylamino-1,1,1-trifluoro-but-3-en-2-ones with hydrogen and 10% Pd/C. (author)

  13. Palladium-catalyzed aryl amination-heck cyclization cascade: A one-flask approach to 3-substituted Indoles

    Jensen, Thomas; Pedersen, Henrik; Bang-Andersen, B.; Madsen, Robert; Jørgensen, Morten

    2008-01-01

    Two for the price of one: A Pd/dppf-based catalyst provides access to the title compounds from 1,2-dihalogenated aromatic compounds and allylic amines in a single reaction flask. The initial aryl amination step occurs with excellent selectivity for the aryl iodide to ensure the formation of a sin...

  14. Iron-catalyzed coupling of aryl sulfamates and aryl/vinyl tosylates with aryl Grignards.

    Agrawal, Toolika; Cook, Silas P

    2014-10-01

    The iron-catalyzed coupling of aryl sulfamates and tosylates with aryl Grignard reagents is reported for the first time. The methodology employs air-stable, low-cost FeF3·3H2O and the N-heterocyclic carbene ligand IPr·HCl as the preligand to form a long-lived catalyst upon treatment with aryl Grignards. The reaction provides a range of cross-coupled products in good-to-excellent yields. In contrast to previous reports with aryl chlorides, these reactions proceed with low levels of Grignard homocoupling regardless of the iron source. PMID:25230097

  15. Synthesis of 3-fluoro-3-aryl oxindoles: Direct enantioselective α arylation of amides

    Wu, Linglin

    2012-02-06

    Modus operandi: Catalytic access to the title compounds through a new asymmetric α-arylation protocol is reported (see scheme). These products are formed in good yields and excellent enantioselectivities by using a new and easily synthesized chiral N-heterocyclic carbene (NHC) ligand. Advanced DFT calculations reveal the properties of the NHC ligand and the mode of operation of the catalyst. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

    2010-07-01

    ...-(substituted phenyl) acetamide. 721.275 Section 721.275 Protection of Environment ENVIRONMENTAL PROTECTION...) acetamide. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide (P-83-1085) is...

  17. Aryl diazonium salts new coupling agents and surface science

    Chehimi, Mohamed Mehdi

    2012-01-01

    Diazonium compounds are employed as a new class of coupling agents to link polymers, biomacromolecules, and other species (e. g. metallic nanoparticles) to the surface of materials. The resulting high performance materials show improved chemical and physical properties and find widespread applications. The advantage of aryl diazonium salts compared to other surface modifiers lies in their ease of preparation, rapid (electro)reduction, large choice of reactive functional groups, and strong aryl-surface covalent bonding.This unique book summarizes the current knowledge of the surface and

  18. Electrochemical cleavage of aryl ethers promoted by sodium borohydride.

    Wu, Wen-Bin; Huang, Jing-Mei

    2014-11-01

    The NaBH4 (or TBABH4)-promoted electrochemically reductive cleavage of aryl C-O bonds in diaryl ethers to produce phenols and arenes with high yields and excellent selectivities at room temperature was reported. Air- and water-tolerable, this process also works on the cleavage of aryl alkyl and benzyl ethers. The application to break the β-O-4, α-O-4, and 4-O-5 lignin model compounds is also illustrated, which highlights the advance toward the goal of lignin conversion. PMID:25317950

  19. Comparative cytotoxicity of N-substituted N'-(4-imidazole-ethyl)thiourea in precision-cut rat liver slices

    In order to more rationally design thiourea-containing drugs and drug candidates, specifically thiourea-containing histamine H3 receptor antagonists, it is necessary to develop structure-toxicity relationships (STRs). For this purpose, the cytotoxicity of a series of thiourea-containing compounds was tested in precision-cut rat liver slices. A concentration of 1000 μM of N-p-bromophenyl, N'-(4-imidazole-ethyl)thiourea (8) or N-p-nitrophenyl, N'-(4-imidazole-ethyl)thiourea (9) was found to cause cytotoxicity, evidenced as LDH leakage, resulting in more than 95% LDH leakage after 6 h. N-p-Methoxyphenyl, N'-(4-imidazole-ethyl)thiourea (6) caused 40.6±19.7% LDH leakage after 6 h. Control levels of cell death (1% methanol as control vehicle) were below 20% in 6 h. After 6 h of exposure, N-p-chlorophenyl, N'-(4-imidazole-ethyl)thiourea (7), 8, and 9 were already found to cause significant cytotoxicity at a concentration of 100 μM. At 200 μM, 9 was found to cause significantly more cytotoxicity than 7 and 8. N-Naphthyl, N'-(4-imidazole-ethyl)thiourea (12) was found to cause significant cytotoxicity towards precision-cut rat liver slices after 6 h of exposure to a concentration of 500 μM. All other N-substituted, N'-(4-imidazole-ethyl)thiourea tested in this study were not found to be cytotoxic towards precision-cut rat liver slices within the 6 h of exposure up to a concentration of 1000 μM. Intracellular glutathione (GSH) content and mitochondrial MTT reduction activity were also examined after exposure of slices to N-substituted, N'-(4-imidazole-ethyl)thiourea. Both of these markers, however, were not found to provide additional information regarding the possible mechanisms of cytotoxicity, i.e. GSH depletion or reduced mitochondrial activity since these markers did not clearly precede LDH leakage. A correlation was found between cytotoxicity towards precision-cut rat liver slices and Vmax/Km values for the formation of sulfenic acids from N-substituted N'-(4-imidazole-ethyl)thiourea by hepatic rat flavin-containing monooxygenases (FMO). The compound with the highest Vmax/Km value for the formation of sulfenic acids, 9, was also the most cytotoxic. Compounds with a significantly lower Vmax/Km value, 7, 8, and 12, were less cytotoxic than 9. Compounds with a Vmax/Km value for the formation of sulfenic acids lower than 0.0788 ml/(min mg) were found not to be cytotoxic towards precision-cut rat liver slices for concentrations up to 1000 μM at an exposure time of 6 h. It is concluded, from this study, that N-phenyl substituted N'-(4-imidazole-ethyl)thiourea-containing electron-withdrawing p-substituents are cytotoxic towards precision-cut rat liver slices. Cytotoxicity is increased with increasing electron-withdrawing capacity of the p-substituent. A correlation was found to exist between Vmax/Km value for the formation of sulfenic acids by rat liver FMO enzymes and cytotoxicity

  20. Aryl substitution of pentacenes

    Andreas R. Waterloo

    2014-07-01

    Full Text Available A series of 11 new pentacene derivatives has been synthesized, with unsymmetrical substitution based on a trialkylsilylethynyl group at the 6-position and various aryl groups appended to the 13-position. The electronic and physical properties of the new pentacene chromophores have been analyzed by UVvis spectroscopy (solution and thin films, thermoanalytical methods (DSC and TGA, cyclic voltammetry, as well as X-ray crystallography (for 8 derivatives. X-ray crystallography has been specifically used to study the influence of unsymmetrical substitution on the solid-state packing of the pentacene derivatives. The obtained results add to our ability to better predict substitution patterns that might be helpful for designing new semiconductors for use in solid-state devices.

  1. New 1-Aryl-3-Substituted Propanol Derivatives as Antimalarial Agents

    Antonio Monge

    2009-10-01

    Full Text Available This paper describes the synthesis and in vitro antimalarial activity against a P. falciparum 3D7 strain of some new 1-aryl-3-substituted propanol derivatives. Twelve of the tested compounds showed an IC50 lower than 1 μM. These compounds were also tested for cytotoxicity in murine J774 macrophages. The most active compounds were evaluated for in vivo activity against P. berghei in a 4-day suppressive test. Compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. In addition, an FBIT test was performed to measure the ability to inhibit ferriprotoporphyrin biocrystallization. This data indicates that 1-aryl-3-substituted propanol derivatives hold promise as a new therapeutic option for the treatment of malaria.

  2. N'-substituted-2'-O,3'-N-carbonimidoyl bridged macrolides: novel anti-inflammatory macrolides without antimicrobial activity.

    Bosnar, Martina; Kragol, Goran; Koštrun, Sanja; Vujasinović, Ines; Bošnjak, Berislav; Bencetić Mihaljević, Vlatka; Marušić Ištuk, Zorica; Kapić, Samra; Hrvačić, Boška; Brajša, Karmen; Tavčar, Branka; Jelić, Dubravko; Glojnarić, Ines; Verbanac, Donatella; Culić, Ognjen; Padovan, Jasna; Alihodžić, Sulejman; Eraković Haber, Vesna; Spaventi, Radan

    2012-07-12

    Macrolide antibiotics, like erythromycin, clarithromycin, and azithromycin, possess anti-inflammatory properties. These properties are considered fundamental to the efficacy of these three macrolides in the treatment of chronic inflammatory diseases like diffuse panbronchiolitis and cystic fibrosis. However, long-term treatment with macrolide antibiotics presents a considerable risk for promotion of bacterial resistance. We have examined antibacterial and anti-inflammatory effects of a novel macrolide class: N'-substituted 2'-O,3'-N-carbonimidoyl bridged erythromycin-derived 14- and 15-membered macrolides. A small focused library was prepared, and compounds without antimicrobial activity, which inhibited IL-6 production, were selected. Data analysis led to a statistical model that could be used for the design of novel anti-inflammatory macrolides. The most promising compound from this library retained the anti-inflammatory activity observed with azithromycin in lipopolysaccharide-induced pulmonary neutrophilia in vivo. Importantly, this study strongly suggests that antimicrobial and anti-inflammatory activities of macrolides are independent and can be separated, which raises development plausibility of novel anti-inflammatory therapeutics. PMID:22697905

  3. Synthesis and characterization of novel N-substituted poly aniline by Triton X-100

    A new N-substituted poly aniline is synthesized by insertion of polyether chain in the form of Triton X-100 onto the poly aniline backbone. In the preparation method, firstly the emeraldine base poly aniline was reacted with Na H to produce the N-anionic doped poly aniline and then contacted with chlorinated Triton X-100. The prepared N-substituted poly aniline was characterized by UV-vis, FTIR, 1H NMR spectroscopy techniques and elemental analysis. The physical properties of synthesized polymer such as electrical conductivity, thermal and electro activity properties were also studied. The prepared polymer has good solubility in common organic solvents such as T HF and chloroform

  4. An efficient synthesis of N-substituted 3-nitrothiophen-2-amines.

    Vivek Kumar, Sundaravel; Muthusubramanian, Shanmugam; Menéndez, J Carlos; Perumal, Subbu

    2015-01-01

    A novel protocol for the synthesis of 3-nitro-N-aryl/alkylthiophen-2-amines in good yields from the reaction of α-nitroketene N,S-aryl/alkylaminoacetals and 1,4-dithiane-2,5-diol in the presence of K2CO3 in refluxing ethanol is described. This transformation generates two C-C bonds in a single operation and presumably proceeds through a reaction sequence comprising 2-mercaptoacetaldehyde generation, nucleophilic carbonyl addition, annelation and elimination steps. PMID:26664589

  5. Synthesis, Antibacterial and Antifungal Activity of 4-Substituted-5-Aryl-1,2,4-Triazoles

    Aleksandra Buzarovska

    2001-09-01

    Full Text Available A few 4-allyl/amino-5-aryl-1,2,4-triazoles were synthesized and tested for antibacterial and antifungal effects against Escherichia coli, Bacillus subtilis, Salmonella enteritidis, Staphylococcus aureus, Aspergillus niger and Candida albicans. 4-Allyl-5-aryl-1,2,4-triazoles were obtained by the oxidative cyclization of the appropriate 1-substituted-4-allylthiosemicarbazides and 4-amino-5-aryl-1,2,4-triazoles were obtained by cyclization of the potassium salts of appropriately substituted dithiocarbazinic acids with hydrazine hydrate. The new synthesized compounds were characterized using IR, 1H- NMR, 13C-NMR and UV spectral data together with elemental analysis.

  6. N-Substitution dependent stereoselectivity switch in palladium catalyzed hydroalkynylation of ynamides: a regio and stereoselective synthesis of ynenamides.

    Dwivedi, Vikas; Babu, Madala Hari; Kant, Ruchir; Reddy, Maddi Sridhar

    2015-10-18

    A highly general palladium catalysed regioselective hydroalkynylation of ynamides for versatile enamide building blocks with an alkyne tether is achieved with an N-substitution dependent stereoselectivity switch under very mild reaction conditions. PMID:26310917

  7. An Expeditious Synthesis of N-substituted Pyrroles via Microwave-Induced Iodine-Catalyzed Reactions under Solventless Conditions

    Debasish Bandyopadhyay

    2010-04-01

    Full Text Available An expeditious synthesis of N-substituted pyrroles has been developed by reacting 2,5-dimethoxy tetrahydrofuran and several amines using a microwave-induced molecular iodine-catalyzed reaction under solventless conditions.

  8. Low Pressure Vinylation of Aryl and Vinyl Halides via Heck-Mizoroki Reactions Using Ethylene

    Smith, Craig R; RajanBabu, T. V.

    2010-01-01

    Aryl bromides and iodides in the presence of catalytic amounts of a palladacycle derived from acetophenone oxime and 2 equivalents of potassium acetate react with ethylene under ambient pressure (15–30 psi) to give the corresponding vinylarenes. The reactions work with both electron-deficient and electron-rich aryl compounds and tolerate wide variety of common functional groups. Vinyl bromides lead to 1,3-dienes in moderate yields.

  9. Smiles Rearrangement Based Practical One-pot Synthesis of N-Alkyl/aryl-6-aminoquinolines from 6-Hydroxylquinoline

    The C-N coupling protocol reported herein represents a convenient and practical synthesis of N-alkyl/aryl-6-aminoquinolines in a three-step one-pot manner by simple addition of 6-hydroxyquinoline and N-alkyl/aryl-2-chloroacetamides with Cs2CO3 or K2CO3 in DMF at 150 .deg. C via Smiles rearrangement. An electron donating substituent on the nitrogen counterpart would accelerate the rearrangement process to achieve various anilines in good yields. We currently engaged in making a chemical library including multifarious N-substituted-6-aminoquinolines, to be used in the screening for specific AChEI activity. Furthermore, this work extends the scope of preparing different heterocyclic synthons in drug design for various biological activities. Aminoquinolines and their derivatives are important chemical entities that are widely used as pro-drugs and drugs due to their antimicrobial, cytotoxic and anti-malarial activities etc

  10. Palladium-catalyzed thiocarbonylation of aryl, vinyl, and benzyl bromides.

    Burhardt, Mia N; Ahlburg, Andreas; Skrydstrup, Troels

    2014-12-19

    A catalytic protocol for synthesis of thioesters from aryl, vinyl, and benzyl bromides as well as benzyl chlorides was developed using only stoichiometric amounts of carbon monoxide, produced from a solid CO precursor inside a two-chamber system. As a catalytic system, the combination of bis(benzonitrile) palladium(II) chloride and Xantphos furnished the highest yields of the desired compounds, along with the weak base, NaOAc, in anisole at 120 °C. The choice of catalytic system as well as solvent turned out to be important in order to ensure a high chemoselectivity in the reaction. Both electron-rich and electron-deficient aryl bromides worked well in this reaction. Addition of 1 equiv of sodium iodide to the reaction improved the chemoselectivity with the electron-deficient aryl bromides. The thiol scope included both aryl and alkyl thiols, including 2-mercaptobenzophenones, whereby a thiocarbonylation followed by a subsequent McMurry coupling yielded differently substituted benzothiophenes. It was demonstrated that the methodology could be applied for (13)C introduction into the thiophene ring. PMID:24919457

  11. Synthesis of N-substituted 6-trifluoromethyl-1,3-oxazinanes

    Nilo, Zanatta; Adriana M. C., Squizani; Leonardo, Fantinel; Fabiane M., Nachtigall; Deise M., Borchhardt; Helio G., Bonacorso; Marcos A. P., Martins.

    2005-12-01

    Full Text Available Este trabalho apresenta a sntese de duas novas sries de 6-trifluormetil-1,3-oxazinanas N-substitudas e 6-trifluormetil-1,3-oxazinan-2-onas N-substitudas, a partir da ciclizao de 4-ilamino-1,1,1-trifluor-butan-2-is com formaldedo e trifosgnio, respectivamente. Os 4-ilamino-1,1,1-trifluor-but [...] an-2-is foram obtidos atravs da reao de reduo dos precursores 4-ilamino-1,1,1-trifluor-but-3-en-2-onas, utilizando hidrognio e 10% Pd/C, com bons rendimentos. Abstract in english This work reports the synthesis of two new series of N-substituted 6-trifluoromethyl-1,3-oxazinanes and N-substituted 6-trifluoromethyl-1,3-oxazinan-2-ones from the cyclization of 4-ylamino-1,1,1-trifluoro-butan-2-ols with formaldehyde and triphosgene, respectively. The 4-ylamino-1,1,1-trifluoro-but [...] an-2-ols were obtained in good yields from the reduction of the parent 4-ylamino-1,1,1-trifluoro-but-3-en-2-ones with hydrogen and 10% Pd/C.

  12. Substituent effect on the photolability of 4-aryl-1,4-dihydropyridines.

    Garca, Cristbal; Cabezas, Karina; Nonell, Santi; Nez-Vergara, Luis J; Morales, Javier; Gnther, Germn; Pizarro, Nancy

    2013-10-01

    The electronic nature of substituents attached to the 4-aryl moiety of 1,4-dihydropyridines strongly affect the photophysical and photochemical behavior of these family of compounds. The presence of an electron-donor substituent on the 4-aryl moiety (or the absence of electron-withdrawing ones), modifies the luminescence lifetimes (? changing more than two orders of magnitude as the polarity is increased. Studies in micellar media allow us to conclude that 4-aryl-1,4-dihydropyridines are located near to the interface, however the surface charge of micelles has no effect on the photodegradation rate constant or the photoproducts profile. The main conclusion of this work is that the photolability of 4-aryl-1,4-dihydropyridines can be significantly reduced by the incorporation of antioxidant moieties. This article is protected by copyright. All rights reserved. PMID:24112052

  13. Three New Sesquiterpene Aryl Esters from the Mycelium of Armillaria mellea

    Chien-Chih Chen

    2015-05-01

    Full Text Available Three new sesquiterpene aryl esters and eight known compounds were isolated from the EtOH extract of the mycelium of Armillaria mellea. The structures of new compounds were established by analysis of their spectroscopic data. Some of the isolates showed cytotoxicity to a variety of cancer cell lines, including MCF-7, H460, HT-29, and CEM.

  14. Practical catalytic asymmetric synthesis of diaryl-, aryl heteroaryl-, and diheteroarylmethanols.

    Salvi, Luca; Kim, Jeung Gon; Walsh, Patrick J

    2009-09-01

    Enantioenriched diaryl-, aryl heteroaryl-, and diheteroarylmethanols exhibit important biological and medicinal properties. One-pot catalytic asymmetric syntheses of these compounds beginning from readily available aryl bromides are introduced. Thus, lithium-bromide exchange with commercially available aryl bromides and n-BuLi was followed by salt metathesis with ZnCl(2) to generate ArZnCl. A second equivalent of n-BuLi was added to form the mixed organozinc, ArZnBu. In the presence of enantioenriched amino alcohol-based catalysts, ArZnBu adds to aldehydes to afford essentially racemic diarylmethanols. The low enantioselectivities were attributed to a LiCl-promoted background reaction. To inhibit this background reaction, the chelating diamine TEEDA (tetraethylethylene diamine) was introduced prior to aldehyde addition. Under these conditions, enantioenriched diarylmethanols were obtained with >90% ee. Arylations of enals generated allylic alcohols with 81-90% ee. This procedure was unsuccessful, however, when applied to heteroaryl bromides, which was attributed to decomposition of the heteroaryl lithium under the salt metathesis conditions. To avoid this problem, the metathesis was conducted with EtZnCl, which enabled the salt metathesis to proceed at low temperatures. The resulting EtZn(Ar(Hetero)) intermediates (Ar(Hetero) = 2- and 3-thiophenyl, 2-benzothiophenyl, 3-furyl, and 5-indolyl) were successfully added to aldehydes and heteroaryl aldehydes with enantioselectivities between 81-99%. These are the first examples of catalytic and highly enantioselective syntheses of diheteroarylmethanols. In a similar fashion, ferrocenyl bromide was used to generate FcZnEt and the ferrocenyl group added to benzaldehyde and heteroaromatic aldehydes to form ferrocene-based ligand precursors in 86-95% yield with 96-98% ee. It was also found that the arylation and heteroarylation of enals could be followed by diastereoselective epoxidations to provide epoxy alcohols with high enantio- and diastereoselectivities in a one-pot procedure. PMID:19653691

  15. Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor

    Milius, R.A.; Saha, J.K.; Madras, B.K.; Neumeyer, J.L. (Research Biochemicals Inc., Natick, MA (USA))

    1991-05-01

    The synthesis and pharmacological characterization of a series of N-substituted 3-(4-fluorophenyl)tropane derivatives is reported. The compounds displayed binding characteristics that paralleled those of cocaine, and several had substantially higher affinity at cocaine recognition sites. Conjugate addition of 4-fluorophenyl magnesium bromide to anhydroecgonine methyl ester gave 2 beta-(carbomethoxy)-3 beta-(4-fluorophenyl)tropane (4a, designated CFT, also known as WIN 35,428) after flash chromatography. N demethylation of 4a was effected by Zn/HOAc reduction of the corresponding 2,2,2-trichloroethyl carbamate to give 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)nortropane (5), which was alkylated with allyl bromide to afford the N-allyl analogue, 6. The N-propyl analogue, 7, was prepared by catalytic reduction (Pd/C) of 6. The most potent analogue, 4a, was tritiated at a specific activity of 81.3 Ci/mmol. ({sup 3}H)4a bound rapidly and reversibly to caudate putamen membranes; the two-component binding curve typical of cocaine analogues was observed. Equilibrium was achieved within 2 h and was stable for at least 4 h. High- and low-affinity Kd values observed for ({sup 3}H)4a (4.7 and 60 nM, respectively) were more than 4 times lower than those for ({sup 3}H)cocaine, and the density of binding sites (Bmax = 50 pmol/g, high, and 290 pmol/g, low) for the two drugs were comparable. Nonspecific binding of ({sup 3}H)4a was 5-10% of total binding.

  16. Electrochemical synthesis and characterization of N-substituted polypyrrole derivatives on nickel

    1-Dodecylpyrrole (PyCH3) and 12-(pyrrol-1-yl)dodecane-1-thiol (PySH) films have been successfully electrochemically polymerised on a nickel electrode from acetonitrile solutions containing the monomer and the lithium perchlorate as supporting electrolyte. The electrochemical study of the polymer growth has been carried out by cyclic voltammetry (CV) detecting the nickel dissolution during electropolymerisation. Several surface spectroscopic and microscopic techniques have been used to characterize the surface in term of chemical composition and polymer topography. The presence of unbound and unoxidised thiol groups at the PPySH surface has been evidenced together with a very strong adhesion to the nickel substrate. Furthermore, N-substituted pyrrole derivatives exhibited some corrosion protection properties in neutral NaCl medium

  17. Synthesis and characterization of methacrylamidopropyltrimethylammonium chloride and N-substituted acrylamide ionomers

    2007-11-01

    Full Text Available Quaternary ammonium ionomers of Methacrylamidopropyltrimethyl ammonium chloride with N-substituted acrylamides were prepared at 551C using azobiscyanovaleric acid (ACVA initiator. The monomers and ionomers were characterized by 1H- and 13C-NMR spectroscopy and the copolymer composition was calculated from elemental analysis data. The reduced viscosity of ionomers in methanol behaves as non-polyelectrolytes at lower mole percentage and as polyelectrolyte at higher mole percentage. The molecular weights of ionomers were found to be high and the polydispersity index values indicate termination mainly by disproportionation. The glass transition temperature (Tg of ionomers were greater than those of the corresponding homopolymers, attributed to a reduction in segmental mobility. The initial decomposition temperature (IDT showed that the stability of ionomers increases with increasing mole percentage of ionic content.

  18. Rh(I)-Catalyzed Direct Arylation of Pyridines and Quinolines

    Berman, Ashley; Lewis, Jared; Bergman, Robert; Ellman, Jonathan

    2008-07-29

    The pyridine and quinoline nuclei are privileged scaffolds that occupy a central role in many medicinally relevant compounds. Consequently, methods for their expeditious functionalization are of immediate interest. However, despite the immense importance of transition-metal catalyzed cross-coupling for the functionalization of aromatic scaffolds, general solutions for coupling 2-pyridyl organometallics with aryl halides have only recently been presented. Direct arylation at the ortho position of pyridine would constitute an even more efficient approach because it eliminates the need for the stoichiometric preparation and isolation of 2-pyridyl organometallics. Progress towards this goal has been achieved by activation of the pyridine nucleus for arylation via conversion to the corresponding pyridine N-oxide or N-iminopyridinium ylide. However, this approach necessitates two additional steps: activation of the pyridine or quinoline starting material, and then unmasking the arylated product. The use of pyridines directly would clearly represent the ideal situation both in terms of cost and simplicity. We now wish to document our efforts in this vein, culminating in an operationally simple Rh(I)-catalyzed direct arylation of pyridines and quinolines. We recently developed an electron-rich Rh(I) system for catalytic alkylation at the ortho position of pyridines and quinolines with alkenes. Therefore, we initially focused our attention on the use of similarly electron-rich Rh(I) catalysts for the proposed direct arylation. After screening an array of electron-rich phosphine ligands and Rh(I) salts, only marginal yields (<20%) of the desired product were obtained. Much more efficient was an electron-poor Rh(I) system with [RhCl(CO){sub 2}]{sub 2} as precatalyst (Table 1). For the direct arylation of picoline with 3,5-dimethyl-bromobenzene, addition of P(OiPr){sub 3} afforded a promising 40% yield of the cross coupled product 1a (entry 1). The exclusion of phosphite additive proved even more effective, with the yield of 1a improving to 61% (entry 2). Further enhancement in yield was not observed upon the inclusion of other additives such as MgO (entry 3), various organic bases (entries 4, 5), or a protic acid source (entry 6). Absolute concentration proved very important, with the best results being obtained at relatively high concentrations of the aryl bromide (compare entries 7 and 8). A marginal improvement was observed upon running the reaction with 6 equivalents of 2-methyl pyridine (entry 9). The reaction temperature could also be increased to 175 or 190 C while maintaining reaction yield, to enable the reaction time to be reduced to 24 h (entries 10 and 11). In summary, we have developed a Rh(I)-catalyzed strategy for the direct arylation of pyridines and quinolines. The heterocycle is used without the need for prefunctionalization, and all reaction components are inexpensive and readily available. The strategy represents an expeditious route to an important class of bis(hetero)aryls and should be of broad utility.

  19. Green and selective synthesis of N-substituted amides using water soluble porphyrazinato copper(II) catalyst

    Ghodsinia, Sara S.E.; Akhlaghinia, Batool; Eshghi, Hossein, E-mail: akhlaghinia@um.ac.ir [Ferdowsi University of Mashhad (Iran, Islamic Republic of). Faculty of Sciences. Department of Chemistry; Safaei, Elham [Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan (Iran, Islamic Republic of). Department of Chemistry

    2013-06-15

    N, N',N{sup ,} N{sup '}-Tetramethyl tetra-2,3-pyridinoporphyrazinato copper(II) methyl sulfate ([Cu(2,3-tmtppa)](MeSO{sub 4}){sub 4}) efficiently catalyzed the direct conversion of nitriles to N-substituted amides. The one pot selective synthesis of the N-substituted amides from nitriles and primary amines was performed in refluxing H{sub 2}O. The catalyst was recovered and reused at least four times, maintaining its efficiency. (author)

  20. A survey of the cleavage of aryl-metal bonds by elemental fluorine

    The reaction of elemental fluorine with phenyl derivatives of tin, lead, germanium, silicon, mercury, and thallium has been studied with the aim of developing a general method for labelling aromatic compounds with radioactive 18F. Rapid synthesis of fluorobenzene was achieved in varying chemical yields up to 70 percent, depending largely upon the metal substrate used, with aryl-tin compounds giving the highest yields. Radiochemical yields are also given for the synthesis of 18/F-fluoro-benzene from the cleavage of aryl-tin bonds with 18F-F2

  1. Involvenflavones A-F, six new flavonoids with 3'-aryl substituent from Selaginella involven.

    Long, Hong-Ping; Zou, Hui; Li, Fu-Shuang; Li, Jing; Luo, Ping; Zou, Zhen-Xing; Hu, Chang-Ping; Xu, Kang-Ping; Tan, Gui-Shan

    2015-09-01

    Six new flavonoids, involvenflavones A-F (1-6), were isolated from Selaginella involven. Their structures were elucidated based on UV, IR, 1D and 2D NMR as well as HR-ESI-MS techniques. All compounds belong to apigenin derivatives with 3'-aryl substituent. This is the first report of the apigenin derivatives with 3'-aryl substituent from nature resources. These compounds also exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro. PMID:26226107

  2. Synthesis, characterization and antibacterial activity of halogenated aryl sulfonamides derived from 2-amino-4-chloroanisole

    In the current work, a number of new N-(5-chloro-2-methoxyphenyl)aryl sulfonamides (3a-e) and N-ethyl/benzyl-N-(5-chloro-2-methoxyphenyl)aryl sulfonamides (6a-e and 7a-e) were synthesized and evaluated for their biological activities. The synthesis was carried out by coupling 2-amino-4-chloroanisole (1) with different aryl sulfonyl chlorides, 2a-e, under dynamic pH control in aqueous medium to form aryl sulfonamides, 3a-e. Further, N-ethyl/benzyl-N-(5-chloro-2-methoxyphenyl)aryl sulfonamides (6a-e and 7a-e) were synthesized by stirring 3a-e with the electrophiles, 4 and 5, in the presence of sodium hydride and N,N-dimethylformamide. The structures of the synthesized compounds were characterized from their spectral data. In addition, the in vitro antibacterial activity of all the target compounds was investigated against Gram-negative and Gram-positive bacteria using ciprofloxacin as a reference drug. Many of these compounds exhibited moderate to good activity and subtle structural changes in the substituents altered the inhibitory properties significantly. (author)

  3. Effects of pesticide compounds (chlorothalonil and mancozeb) and benzo[a]pyrene mixture on aryl hydrocarbon receptor, p53 and ubiquitin gene expression levels in haemocytes of soft-shell clams (Mya arenaria).

    Pariseau, Julie; McKenna, Patricia; Aboelkhair, Mohammed; Saint-Louis, Richard; Pelletier, Emilien; Davidson, T Jeffrey; Tremblay, Rjean; Berthe, Franck C J; Siah, Ahmed

    2011-11-01

    The aim of this study is to investigate the effects of the pesticides/polycyclic aromatic hydrocarbon mixture on aryl hydrocarbon receptor (AhR), p53 and ubiquitin mRNA level in haemocytes of Mya arenaria exposed to a mixture of chlorothalonil, mancozeb and benzo[a]pyrene (BaP) for 48 and 72 h. AhR, p53 and ubiquitin gene expression levels were quantified using quantitative Real-time PCR. For robust and accurate quantification of transcripts, suitable housekeeping genes were selected from four sets of ribosomal and elongation factors transcripts previously sequenced from Mya arenaria using geNorm open source software. Quantitative Real-time PCR data exhibited a significantly high expression of AhR after 72 h of exposure (P ? 0.05). p53 gene expression seems to be up-regulated by the mixture after 48 h, however not significantly; but the level of p53 mRNA is down-regulated by the xenobiotics between 48 and 72 h after exposure. This study postulates that AhR mRNA levels could be used as an indicator of the exposure of clams' haemocytes to a mixture of xenobiotics such as chlorothalonil, mancozeb and BaP. However, further studies have to be pursued in order to unravel the molecular mechanisms involved in the p53 signaling pathway. PMID:21688059

  4. A direct method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels

    Boopathy Rathanam

    2000-12-01

    Full Text Available Abstract Background In vertebrates, two types of cholinesterases exist, acetylcholinesterase and butyrylcholinesterase. The function of acetylcholinesterase is to hydrolyse acetylcholine, thereby terminating the neurotransmission at cholinergic synapse, while the precise physiological function of butyrylcholinesterase has not been identified. The presence of cholinesterases in tissues that are not cholinergically innervated indicate that cholinesterases may have functions unrelated to neurotransmission. Furthermore, cholinesterases display a genuine aryl acylamidase activity apart from their predominant acylcholine hydrolase activity. The physiological significance of this aryl acylamidase activity is also not known. The study on the aryl acylamidase has been, in part hampered by the lack of a specific method to visualise this activity. We have developed a method to visualise the aryl acylamidase activity on cholinesterase in polyacrylamide gels. Results The o-nitroaniline liberated from o-nitroacetanilide by the action of aryl acylamidase activity on cholinesterases, in the presence of nitrous acid formed a diazonium compound. This compound gave an azo dye complex with N-(1-napthyl-ethylenediamine, which appeared as purple bands in polyacrylamide gels. Treating the stained gels with trichloroacetic acid followed by Tris-HCl buffer helped in fixation of the stain in the gels. By using specific inhibitors for acetylcholinesterase and butyrylcholinesterase, respectively, differential staining for the aryl acylamidase activities on butyrylcholinesterase and acetylcholinesterase in a sample containing both these enzymes has been demonstrated. A linear relationship between the intensity of colour developed and activity of the enzyme was obtained. Conclusions A novel method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels has been developed.

  5. Antibacterial and Enzyme Inhibition Studies of N'-Substituted Benzylidene-2-(2, 4-Dimethylphenoxy Acetatohydrazides

    1S. Nadeem

    2014-09-01

    Full Text Available The molecules bearing azomethine group are known to possess biological activities. In the present work, the synthesis of N'-Substitutedbenzylidene-2-(2, 4-dimethylphenoxy acetatohydrazide (5a-d has been elaborated using 2,4-Dimethylphenol (1 as precursor. The molecule, 1, was converted to ethyl 2-(2,4-dimethylphenoxyacetate (2 on refluxing with ethyl 2-bromoacetate in ethanol in the presence of KOH. Ethyl ester, 2, was refluxed with hydrated hydrazine (80% in ethanol to yield 2-(2,4-dimethylphenoxy acetohydrazide (3. The target molecules, 5a-d, were synthesized by stirring 3 with phenyl/aryl carboxaldehyde (4a-d in methanol in the presence of glacial acetic acid. The synthesized molecules were characterized by spectral data and evaluated for antibacterial and anti-enzymatic activities.

  6. Synthesis of N-substituted phthalimides and their antifungal activity against Alternaria solani and Botrytis cinerea.

    Pan, Le; Li, Xiuzhuang; Gong, Chengwen; Jin, Hui; Qin, Bo

    2016-06-01

    As organosulfur and organophosphorus agents, phaltane and phosmet are facing great challenges for the environmental contamination, mammalian toxicity and increasing resistance with long term use. It is efficient and meaningful to develop phthalimide-based alternatives with non-sulfur and non-phosphorus groups. A series of N-substituted phthalimides were synthesized and their antifungal activity against two disastrous phytopathogenic fungi, Alternaria solani and Botrytis cinerea was evaluated in vitro. Most of them showed significant antifungal activity against both of fungi, or either of them selectively. N-vinylphthalimide (4) and 8-[4-(phthalimide-2-yl) butyloxy] quinoline (13) were identified as the most promising candidates against B. cinerea and A. solani with the IC50 values of 7.92 μg/mL and 10.85 μg/mL respectively. The brief structure-activity relationships have revealed that vinyl, quinolyl, bromide alkyl and benzyl substitutions were appropriate substituents and coupling functional moieties indirectly with optimum alkyl chain was efficient to prepare phthalimides related fungicides. PMID:27079471

  7. ON THE ANTIOXIDANT EFFECTIVENESS OF N,NSUBSTITUTED P-PHENYLENEDIAMINES

    Vladimr Luke

    2004-10-01

    Full Text Available The ground-state geometry of six N,N-substituted p-phenylenediamines (PPDs: N-phenyl-N-dimethyl-butyl-p-phenylenediamine (6PPD, N-phenyl-N-isopropyl-p-phenylenediamine (IPPD, N-phenyl-N-(?-methylbenzyl-p-phenylenediamine (SPPD, N-(2-methoxybenzyl-N-phenyl-p-phenylenediamine (MBPPD, N-benzyl-N-phenyl-p-phenylenediamine (MBPPDH, N-(1-methyl-1-phenylethyl-N-phenyl-p-phenylene-diamine (CPPD molecules, their radical structures and the energy characterisation of these molecules and radicals were theoretically investigated using PM3 method. Our calculations reveal the most probable radical formation in the order SPPD > MBPPD > MBPPDH > 6PPD > IPPD > CPPD. The theoretical values have been compared with the values obtained by the analysis of structural units contributions based on the results of non-isothermal DSC measurements. The results show that the most likely process is homolytic cleavage of CH bond at the carbon atom in the neighbourhood of the amino nitrogen atom and the sterical arrangement is related to the antioxidant effectiveness of the antioxidants under study. The suggested models can be used for the interpretation and prediction of experimental data what is important from the technological point of view.

  8. N-substituted aminomethanephosphonic and aminomethane-P-methylphosphinic acids as inhibitors of ureases.

    Berlicki, Lukasz; Bochno, Marta; Grabowiecka, Agnieszka; Białas, Arkadiusz; Kosikowska, Paulina; Kafarski, Paweł

    2012-05-01

    Small unextended molecules based on the diamidophosphate structure with a covalent carbon-to-phosphorus bond to improve hydrolytic stability were developed as a novel group of inhibitors to control microbial urea decomposition. Applying a structure-based inhibitor design approach using available crystal structures of bacterial urease, N-substituted derivatives of aminomethylphosphonic and P-methyl-aminomethylphosphinic acids were designed and synthesized. In inhibition studies using urease from Bacillus pasteurii and Canavalia ensiformis, the N,N-dimethyl derivatives of both lead structures were most effective with dissociation constants in the low micromolar range (Ki=13±0.8 and 0.62±0.09 μM, respectively). Whole-cell studies on a ureolytic strain of Proteus mirabilis showed the high efficiency of N,N-dimethyl and N-methyl derivatives of aminomethane-P-methylphosphinic acids for urease inhibition in pathogenic bacteria. The high hydrolytic stability of selected inhibitors was confirmed over a period of 30 days using NMR technique. PMID:21559954

  9. Design and synthesis of N-aryl isothioureas as a novel class of gastric H(+) /K(+) -ATPase inhibitors.

    Ma, Chao; Wu, Anhui; Wu, Yongqi; Ren, Xuhong; Cheng, Maosheng

    2013-12-01

    To find new H(+) /K(+) -ATPase inhibitors for the treatment of peptic ulcer disease, a series of novel N-aryl isothiourea derivatives were synthesized and their structures were identified by (1) H NMR and GC-MS. The effects of these compounds on inhibiting gastric acid secretion were evaluated by the guinea pig stomach mucous membrane study with pantoprazole magnesium as a positive control. The results showed that, of the 37 N-aryl isothiourea compounds synthesized, 20 compounds have comparable or stronger gastric acid inhibitory activities than that of pantoprazole magnesium. The quantitative structure-activity relationships (QSARs) of the N-aryl isothiourea compounds were also studied by comparative molecular field analysis (CoMFA) computation, and the model structure that was supposed to give more powerful bioactivities was finally predicted. PMID:24301963

  10. Testing for partial agonism of the aryl hydrocarbon receptor

    Wall, Richard J

    2008-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent of a group of persistent organic pollutants (POPs). The aryl hydrocarbon receptor (AhR) has a high affinity for these dioxin-like compounds with activation increasing transcription of CYP1A1. The aim of this paper was to measure the agonistic and potential antagonistic effects of four of the most prevalent and potent dioxin-like agonists: 3-Methylcholanthrene (3-MC), 2,3,7,8-Tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-Pentachlorodibe...

  11. Radioiodination of Aryl-Alkyl Cyclic Sulfates

    Mikhail I. Papisov

    2012-11-01

    Full Text Available Among the currently available positron emitters suitable for Positron Emission Tomography (PET, 124I has the longest physical half-life (4.2 days. The long half-life and well-investigated behavior of iodine in vivo makes 124I very attractive for pharmacological studies. In this communication, we describe a simple yet effective method for the synthesis of novel 124I labeled compounds intended for PET imaging of arylsulfatase activity in vivo. Arylsulfatases have important biological functions, and genetic deficiencies of such functions require pharmacological replacement, the efficacy of which must be properly and non-invasively evaluated. These enzymes, even though their natural substrates are mostly of aliphatic nature, hydrolyze phenolic sulfates to phenol and sulfuric acid. The availability of [124I]iodinated substrates is expected to provide a PET-based method for measuring their activity in vivo. The currently available methods of synthesis of iodinated arylsulfates usually require either introducing of a protected sulfate ester early in the synthesis or introduction of sulfate group at the end of synthesis in a separate step. The described method gives the desired product in one step from an aryl-alkyl cyclic sulfate. When treated with iodide, the source cyclic sulfate opens with substitution of iodide at the alkyl center and gives the desired arylsulfate monoester.

  12. Anti-Candida activity and cytotoxicity of a large library of new N-substituted-1,3-thiazolidin-4-one derivatives.

    De Monte, Celeste; Carradori, Simone; Bizzarri, Bruna; Bolasco, Adriana; Caprara, Federica; Mollica, Adriano; Rivanera, Daniela; Mari, Emanuela; Zicari, Alessandra; Akdemir, Atilla; Secci, Daniela

    2016-01-01

    On the basis of the recent findings about the biological properties of thiazolidinones and taking into account the encouraging results about the antifungal activity of some (thiazol-2-yl)hydrazines, new N-substituted heterocyclic derivatives were designed combining the thiazolidinone nucleus with the hydrazonic portion. In details, 1,3-thiazolidin-4-ones bearing (cyclo)aliphatic or (hetero)aromatic moieties linked to the N1-hydrazine at C2 were synthesized and classified into three series according to the aromatic or bicyclic rings connected to the lactam nitrogen of the thiazolidinone. These molecules were assayed for their anti-Candida effects in reference to the biological activity of the conventional topic (clotrimazole, miconazole, tioconazole) and systemic drugs (fluconazole, ketoconazole, amphotericin B). Finally, we investigated the selectivity against fungal cells by testing the compounds endowed with the best MICs on Hep2 cells in order to assess their cell toxicity (CC50) and we noticed that two derivatives were less cytotoxic than the reference drug clotrimazole. Moreover, a preliminary molecular modelling approach has been performed against lanosterol 14-? demethylase (CYP51A1) to rationalize the activity of the tested compounds and to specify the target protein or enzyme. PMID:26562544

  13. Solvent-Free Synthesis, DNA-Topoisomerase II Activity and Molecular Docking Study of New Asymmetrically N,N'-Substituted Ureas

    Aurea Echevarria

    2012-11-01

    Full Text Available A new series of asymmetrically N,N'-substituted ureas 20–25 was prepared using solvent free conditions, which is an eco-friendly methodology, starting with Schiff bases derived from cinnamaldehyde and p-substituted anilines, which are subsequently submitted to reduction reactions that afford the corresponding asymmetric secondary amines. All of the intermediates were prepared using solvent free reactions, which were compared to traditional methodologies. All of the reactions required a remarkably short amount of time and provided good yields when solvent free conditions were employed compared to other methodologies. The DNA-topoisomerase II-α (topo II-α activity was evaluated in relaxation assays, which showed that all of the compounds inhibited the enzyme activity at 10 μM, except for urea 24. Furthermore, a molecular docking study indicated that the compounds 20–25 binding to the topo II-α are able to interact with the same binding site as the anticancer drug etoposide, suggesting that the ureas could inhibit the enzyme by the same mechanism of action observed for etoposide, which prevents re-ligation of the DNA strands.

  14. Synthesis and characterisation of new 4-oxo-N-(substituted-thiazol-2-yl)-4H-chromene-2-carboxamides as potential adenosine receptor ligands

    Cagide, Fernando; Borges, Fernanda; Gomes, Ligia R.; Low, John Nicolson

    2015-06-01

    Chromones are 4H-benzopyran-4-one heterocycles that have been thoroughly studied due to their interesting biological activities. Thiazole based compounds have been used in therapeutics as antimicrobial, antiviral and as antifungal agents for a long time but, in the past decades, they have been identified as potent and selective ligands for adenosine receptor. In continuation of our project related to the syntheses of pharmacologically important heterocycles, a new series of chromone-thiazole hybrids have been designed as potential ligands for human adenosine receptors. In this context, new 4-oxo-N-(substituted-thiazol-2-yl)-4H-chromene-2-carboxamides were synthesized from chromone-2-carboxylic acid by two different amidation methods. The development of dissimilar synthetic approaches provided the possibility of working with diverse reaction conditions, namely with conventional heating and/or microwave irradiation. The structure of the compounds has been established on the basis of NMR and MS spectroscopy and X-ray crystallography. Relevant data related to the molecular geometry and conformation of the chromone-thiazole hybrids has been acquired which can be of the utmost importance to understand ligand-receptor binding.

  15. Synthesis and antifungal activity of novel (1-aryl-2-heterocyclyl)ethylideneaminooxymethyl-substituted dioxolanes

    Baji, H.; Flammang, M.; Kimny, T.; Gasquez, F.; Compagnon, P.L.; Delcourt, A. [Dijon Univ., 21 (France)

    1995-12-31

    A novel series of (1-aryl-2-heterocyclyl)ethylideneaminooxymethyl -substituted dioxolanes IIIa-n were synthesized by condensation of substituted 1,3-dioxolan-4-ylmethyl p-toluenesulfonates 4 with 1-(hydroxyimino)-1-aryl-2-heterocyclylethanes 5. Compounds IIIa-n were found to have effective in vitro antifungal activity when evaluated against the pathogenic fungi Candida albicans, Aspergillus flavus and Fusarium solani with MIC (minimum inhibitory concentration) values of 10 {mu}g-ml{sup -1} for IIIa-I and 5 {mu}g-ml{sup -1} for IIIm,n. (authors). 24 refs., 4 figs., 5 tabs.

  16. Synthesis and antifungal activity of novel (1-aryl-2-heterocyclyl)ethylideneaminooxymethyl-substituted dioxolanes

    A novel series of (1-aryl-2-heterocyclyl)ethylideneaminooxymethyl -substituted dioxolanes IIIa-n were synthesized by condensation of substituted 1,3-dioxolan-4-ylmethyl p-toluenesulfonates 4 with 1-(hydroxyimino)-1-aryl-2-heterocyclylethanes 5. Compounds IIIa-n were found to have effective in vitro antifungal activity when evaluated against the pathogenic fungi Candida albicans, Aspergillus flavus and Fusarium solani with MIC (minimum inhibitory concentration) values of 10 μg-ml-1 for IIIa-I and 5 μg-ml-1 for IIIm,n. (authors). 24 refs., 4 figs., 5 tabs

  17. Synthesis of Dimethyl Aryl Acylsulfonium Bromides from Aryl Methyl Ketones in a DMSO-HBr System

    Zhiling Cao; Dahua Shi; Yingying Qu; Chuanzhou Tao; Weiwei Liu; Guowei Yao

    2013-01-01

    A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO). This sulfonium salt confirms that bromine production and the bromination reaction take place in the DMSO-HBr oxidation system. What’s more, it is also a key intermediate for the synthesis of arylglyoxals.

  18. Synthesis of Dimethyl Aryl Acylsulfonium Bromides from Aryl Methyl Ketones in a DMSO-HBr System

    Zhiling Cao

    2013-12-01

    Full Text Available A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO. This sulfonium salt confirms that bromine production and the bromination reaction take place in the DMSO-HBr oxidation system. What’s more, it is also a key intermediate for the synthesis of arylglyoxals.

  19. SYNTHESIS AND ANTIMICROBIAL EVALUATION OF 2-(4-FLUORO BENZYLTHIO-N-(SUBSTITUTED PHENYLPYRIMIDINE-4-AMINES

    N.M. Goudgaon*, Y. Rohini Reddy and B.U. Sheshikant

    2013-11-01

    Full Text Available Reaction of 4-fluorobenzylchloride with 2-thiouracil (1 gave 2-(4-fluorobenzylthiopyrimidin-4(3H-one (2, which on chlorination with POCl3 furnished 4-chloro-2-(4-fluorobenzylthio-4-chloropyrimidine (3. This intermediate when treated with various substituted anilines gave desired targeted compounds 4(a-k in 50-90% yield. Structural assignments of the synthesized compounds were based on their IR, 1H NMR, Mass and analytical data. The antimicrobial evaluation of newly synthesized compounds was carried out by cup-plate method. The investigation of antimicrobial screening reveals that the compounds 4b, 4g, 4c and 4f showed good activity against bacterial strain B. subtilis. Compounds 4a, 4e, 4b, 4c, 4f, 4g and 4h were active against bacterial strain P. aeruginosa. Compounds 4a and 4c were active against fungul strain A. niger. Compounds 4e, 4b and 4j showed good activity against fungal strain A. flavus. All the synthesized compounds showed excellent antifungal activity against T.viridae. Remaining compounds exhibited moderate to poor activity against bacterial and fungal strains when compared to standard drugs Gentamycin and Fluconazole respectively. So, further we have carried out the antifungal screening of all the synthesized compounds at different concentrations against T. viridae to determine their IC50 values. Compounds 4e, 4b, 4g, 4i, 4d, 4f and 4j have shown better IC50 values.

  20. Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

    Henok H. Kinfe

    2015-04-01

    Full Text Available 1-C and 2-C-branched carbohydrates are present as substructures in a number of biologically important compounds. Although the synthesis of such carbohydrate derivatives is extensively studied, the synthesis of 1,2-cis-2-C-branched C-, S-, and N-glycosides is less explored. In this article a synthetic strategy for the synthesis of 1,2-cis-2-C-branched-aryl-C-glucosides is reported via a hydrogenolytic desulfurization of suitably orientated carbohydrate based hemithioacetals. 1,2-cis-2-Hydroxymethyl and 2-carbaldehyde of aryl-C-glucosides have been synthesized using the current strategy in very good yields. The 2-carbaldehyde-aryl-C-glucosides have been identified as suitable substrates for the stereospecific preparation of 2,3-unsaturated-aryl-C-glycosides (Ferrier products.

  1. Discovery of novel N-aryl piperazine CXCR4 antagonists.

    Zhao, Huanyu; Prosser, Anthony R; Liotta, Dennis C; Wilson, Lawrence J

    2015-11-01

    A novel series of CXCR4 antagonists with substituted piperazines as benzimidazole replacements is described. These compounds showed micromolar to nanomolar potency in CXCR4-mediated functional and HIV assays, namely inhibition of X4 HIV-1(IIIB) virus in MAGI-CCR5/CXCR4 cells and inhibition of SDF-1 induced calcium release in Chem-1 cells. Preliminary SAR investigations led to the identification of a series of N-aryl piperazines as the most potent compounds. Results show SAR that indicates type and position of the aromatic ring, as well as type of linker and stereochemistry are significant for activity. Profiling of several lead compounds showed that one (49b) reduced susceptibility towards CYP450 and hERG, and the best overall profile when considering both SDF-1 and HIV potencies (6-20 nM). PMID:25935642

  2. Novel aryl carbamate derivatives of metronidazole as potential antiamoebic agents.

    Hayat, Faisal; Wahedi, Hussain Mustatab; Park, Seonghyeok; Tariq, Saba; Azam, Amir; Shin, Dongyun

    2016-01-01

    A series of novel aryl carbamate derivatives of metronidazole (MNZ) were designed, synthesized, and screened for antiamoebic activity. As compared to MNZ, most of the derivatives exhibited moderate to excellent activity against the HM1:IMSS strain of Entamoeba histolytica. Compounds 7, 14, 16, 19, and 21 exhibited the most promising antiamoebic activity with IC50 values of 0.24, 0.08, 0.26, 0.26, and 0.15?M, respectively, compared to that of MNZ (1.78?M). Moreover, from the toxicological studies of these compounds on human melanocytes, the melan-a cell line revealed that the potent compounds are nontoxic at concentrations ranging from 2.5 to 50?M. PMID:26597858

  3. Synthesis and biological evaluation of novel dioxa-bicycle C-aryl glucosides as SGLT2 inhibitors.

    Yan, Qi; Ding, Ning; Li, Yingxia

    2016-02-01

    A series of novel C-aryl glucosides containing dioxa-bicycle were synthesized and evaluated for inhibition activity against hSGLT2. Among the compounds tested, compound 6a showed moderate SGLT2 inhibition activities at 700 nM. The results could benefit the discovery of new SGLT2 inhibitors. PMID:26735747

  4. Anaerobic Aryl Reductive Dehalogenation of Halobenzoates by Cell Extracts of "Desulfomonile tiedjei".

    Deweerd, K A; Suflita, J M

    1990-10-01

    We studied the transformation of halogenated benzoates by cell extracts of a dehalogenating anaerobe, "Desulfomonile tiedjei." We found that cell extracts possessed aryl reductive dehalogenation activity. The activity was heat labile and dependent on the addition of reduced methyl viologen, but not on that of reduced NAD, NADP, flavin mononucleotide, flavin adenine dinucleotide, desulfoviridin, cytochrome c(3), or benzyl viologen. Dehalogenation activity in extracts was stimulated by formate, CO, or H(2), but not by pyruvate plus coenzyme A or by dithionite. The pH and temperature optima for aryl dehalogenation were 8.2 and 35 degrees C, respectively. The rate of dehalogenation was proportional to the amount of protein in the assay mixture. The substrate specificity of aryl dehalogenation activity for various aromatic compounds in "D. tiedjei" cell extracts was identical to that of whole cells, except differences were observed in the relative rates of halobenzoate transformation. Dehalogenation was 10-fold greater in "D. tiedjei" extracts prepared from cells cultured in the presence of 3-chlorobenzoate, suggesting that the activity was inducible. Aryl reductive dehalogenation in extracts was inhibited by sulfite, sulfide, and thiosulfate, but not sulfate. Experiments with combinations of substrates suggested that cell extracts dehalogenated 3-iodobenzoate more readily than either 3,5-dichlorobenzoate or 3-chlorobenzoate. Dehalogenation activity was found to be membrane associated. This is the first report characterizing aryl dehalogenation activity in cell extracts of an obligate anaerobe. PMID:16348308

  5. Anaerobic aryl reductive dehalogenation of halobenzoates by cell extracts of Desulfomonile tiedjei

    DeWeerd, K.A.; Suflita, J.M. (Univ. of Oklahoma, Norman (USA))

    1990-10-01

    The authors studied the transformation of halogenated benzoates by cell extracts of a dehalogenating anaerobe, Desulfomonile tiedjei. The authors found that cell extracts possessed aryl reductive dehalogenation activity. The activity was heat labile and dependent on the addition of reduced methyl viologen, but not on that of reduced NAD, NADP, flavin mononucleotide, flavin adenine dinucleotide, desulfoviridin, cytochrome c{sub 3}, or benzyl viologen. Dehalogenation activity in extracts was stimulated by formate, CO, or H{sub 2}, but not by pyruvate plus coenzyme A or by dithionite. The pH and temperature optima for aryl dehalogenation were 8.2 and 35{degree}C, respectively. The rate of dehalogenation was proportional to the amount of protein in the assay mixture. The substrate specificity of aryl dehalogenation activity for various aromatic compounds in D. tiedjei cell extracts was identical to that of whole cells, except differences were observed in the relative rates of halobenzoate transformation. Dehalogenation was 10-fold greater in D. tiedjei extracts prepared from cells cultured in the presence of 3-chlorobenzoate, suggesting that the activity was inducible. Aryl reductive dehalogenation in extracts was inhibited by sulfite, sulfide, and thiosulfate, but not sulfate. Experiments with combinations of substrates suggested that cell extracts dehalogenated 3-iodobenzoate more readily than either 3,5-dichlorobenzoate or 3-chlorobenzoate. Dehalogenation activity was found to be membrane associated. This is the first report characterizing aryl dehalogenation activity in cell extracts of an obligate anaerobe.

  6. Comparative study of spectroscopic properties of the low-lying electronic states of 2,4-pentadien-1-iminium cation and its N-substituted analogues

    Anjan Chattopadhyay

    2012-09-01

    Semiempirical and ab initio-based CI methods have been employed to study the low-lying electronic states of 2,4-pentadien-1-iminium cation and its N-substituted analogues with electron-donating (methyl, isopropyl) and electron-withdrawing (fluoromethyl) groups on nitrogen. Variations of the dihedral angles (Γ3, Γ4) of the ground state have given the global minima and global maxima at (180°, 180°) and (90°, 0°) conformations, respectively, with some exceptions in the case of fluoromethyl compound. Increase in the +I effect on nitrogen shifts the TICT conical intersection point away from the 90° (Γ3 dihedral angle) value, when the Γ4 value is kept fixed at 180°. Transition moment values of the allowed S0(1A -like) → S1 (2B-like) transitions are expectedly higher than the forbidden S0(1A -like) → S2(2A -like) transitions by almost 5.6 D. Radiative lifetime values of the first excited states are calculated to be around 215 ps for all the four compounds. At (180°, 180°) conformation the vertical excitation energy (VEE) between the S0 and S1 states of the 2,4-pentadieniminium cation is found to be 3.3 eV, which corresponds to the absorption wavelength value of roughly 375 nm. The VEE value increases with substituents having +I effect on nitrogen, while for the fluoromethyl compound it is calculated to be around 2.85 eV. The energy gap between the first two excited singlet states is found to have the least value in the isopropyl-substituted compound, where the S2 state contains a huge contribution from the HOMO2→LUMO2 configuration.

  7. Palladium-catalysed ortho arylation of acetanilides

    Guo-zhen zhang; Cheng-Qun Chen; Xin-Hua Feng; Guo-Sheng Huang

    2010-03-01

    The palladium-catalysed direct arylation of acetanilides by using C-H activation methodology has been demonstrated. Several acetanilides were coupled with aryl iodides in the presence of 10 mol% of Pd(OAc)2, 1.0 equiv of Cu(OTf)2, and 0.6 equiv of Ag2O to afford the corresponding products in moderate to excellent yields. The results showed that the amount of Ag2O was important for this protocol.

  8. Synthesis and antileishmanial activity of new 1-Aryl-1H-Pyrazole-4- carboximidamides derivatives

    Santos, Mauricio S. dos; Gomes, Adriana O.; Bernardino, Alice M.R.; Souza, Marcos C. de, E-mail: alicerolim@globo.co [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Programa de Pos-Graduacao em Quimica Organica; Khan, Misbahul A. [The Islamia University of Bahawalpur (Pakistan). Chemistry Dept.; Brito, Monique A. de [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Fac. de Farmacia. Lab. de Quimica Medicinal Computacional; Castro, Helena C.; Abreu, Paula A. [Universidade Federal Fluminense (LABioMol/GCM/UFF), Niteroi, RJ (Brazil). Inst. de Biologia. Lab. de Antibioticos, Bioquimica e Modelagem Molecular; Rodrigues, Carlos R. [Universidade Federal do Rio de Janeiro (ModMol/UFRJ), RJ (Brazil). Fac. de Farmacia. Lab. de Modelagem Molecular e QSAR; Leo, Rosa M.M. de; Leon, Leonor L.; Canto-Cavalheiro, Marilene M. [Fundacao Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, RJ (Brazil). Instituto Oswaldo Cruz. Lab. de Bioquimica de Tripanosomatideos

    2011-07-01

    Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies. (author)

  9. Synthesis and antileishmanial activity of new 1-Aryl-1H-Pyrazole-4- carboximidamides derivatives

    Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies. (author)

  10. Role of the aryl hydrocarbon receptor in cell cycle regulation

    One of the most puzzling aspects of the biological impact of polycyclic aromatic hydrocarbon compounds is that they elicit an apparently unrelated variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans. At the cellular level, these environmental toxicants affect cell cycle regulatory mechanisms and signal transduction pathways in ways that are equally diverse and often contradictory. For example, depending on the particular cell lines studied, exposure to these compounds may lead to cell proliferation, to terminal differentiation, or to apoptosis. These effects are mediated by the aryl hydrocarbon receptor, a ligand-activated transcription factor well known for its regulatory activity on the expression of several phase I detoxification cytochrome P450 genes. Research into the molecular mechanisms of aryl hydrocarbon receptor function has uncovered a novel role for this protein during cell cycle progression. The activated receptor acts as an environmental sensor and cell cycle checkpoint that commits cells exposed to adverse environmental stimuli to arrest before the onset of DNA replication

  11. Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo; Loddo, Roberta

    2007-01-01

    The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate...

  12. Toxicity Studies on Novel N-Substituted Bicyclo-Heptan-2-Amines at NMDA Receptors

    Michelle Farbaniec

    2013-04-01

    Full Text Available Several novel norcamphor derivatives were designed and synthesized as uncompetitive NMDA receptor antagonists at the phencyclidine (PCP binding site. Such compounds have potential as ligands for understanding and possibly the treatment of several neurodegenerative disorders and other glutamate-dependent disorders. We examined the toxic effects of the compounds as compared with memantine, an NMDA receptor antagonist that is FDA approved for treatment of Alzheimer’s disease, by testing these compounds on two cell lines: MDCK (to mimic blood brain barrier and N2a (a neuronal cell line. The compounds showed toxicity profiles similar to those of memantine i.e., dose dependence above 100 μM and IC50 values above 150 μM for each cell line. It is known that the serum level of memantine under therapeutic conditions in patients is about 1 µM, indicting these compounds could have acceptable therapeutic indexes. 2-Phenyl-N-(2-(piperidin-1-yl ethylbicyclo[2.2.1]heptan-2-amine (5a was found to possess acceptable toxicity profiles in both cell lines. Interestingly, this was the compound identified as a good lead in our previous studies based on binding and anticonvulsant (MES activity studies. It has thus emerged as an excellent lead compound for further studies.

  13. Convenient preparation of deuterium-labeled analogs of peptides containing N-substituted glycines for a stable isotope dilution LC-MS quantitative analysis.

    B?chor, Remigiusz; D?bowski, Dawid; ??gowska, Anna; Stefanowicz, Piotr; Rolka, Krzysztof; Szewczuk, Zbigniew

    2015-11-01

    N-substituted glycines constitute mimics of natural amino acids that are of great interest in the peptide-based drug development. Peptoids-oligo(N-substituted glycines) have been recently demonstrated to be highly active peptidomimetics in biological systems, resistant to proteolytic degradation. We developed a method of the deuterium labeling of peptidomimetics containing N-substituted glycine residues via H/D exchange of their ?-carbon hydrogen atoms. The labeling was shown to be easy, inexpensive, and without the use of derivatization reagents or the need for a further purification. The deuterons introduced at the ?-carbon atoms do not undergo a back exchange under acidic conditions during liquid chromatography mass spectrometry (LC-MS) analysis. The LC-MS analysis of a mixture of isotopologues revealed a co-elution of deuterated and nondeuterated forms of the peptidomimetics, which may be useful in the quantitative isotope dilution analysis of peptoids and other derivatives of N-substituted glycines. PMID:26415697

  14. Optimized Anti-pathogenic Agents Based on Core/Shell Nanostructures and 2-((4-Ethylphenoxyethyl-N-(substituted-phenylcarbamothioyl-benzamides

    Mariana Carmen Chifiriuc

    2012-10-01

    Full Text Available The purpose of this study was to design a new nanosystem for catheter surface functionalization with an improved resistance to Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 colonization and subsequent biofilm development. New 2-((4 ethylphenoxymethyl-N-(substituted-phenylcarbamothioyl-benzamides were synthesized and used for coating a core/shell nanostructure. Their chemical structures were elucidated by NMR, IR and elemental analysis, being in agreement with the proposed ones. Fe3O4/C12 of up to 5 nm size had been synthesized with lauric acid as a coating agent and characterized by XRD, FT-IR, TGA, TEM and biological assays. The catheter pieces were coated with the fabricated nanofluid in magnetic field. The microbial adherence ability was investigated in 6 multiwell plates by using culture based methods and Scanning Electron Microscopy (SEM. The nanoparticles coated with the obtained compounds 1ac inhibited the adherence and biofilm development ability of the S. aureus and P. aeruginosa tested strains on the catheter functionalized surface, as shown by the reduction of viable cell counts and SEM examination of the biofilm architecture. Using the novel core/shell/adsorption-shell to inhibit the microbial adherence could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with improved anti-biofilm properties.

  15. ¬Enzyme Inhibition Studies on N-Substituted Sulfonamides Derived from m-phenetidine

    *Aziz-ur-Rehman

    2013-06-01

    Full Text Available Organic synthesis of various compounds followed by biological activities is the going on methodology in the world for pharmacological evaluation. The undertaken research is the synthesis of N-(3-ethoxyphenyl-4-methylbenzenesulfonamide (3 through condensation reaction of m-phenetidine (1 and 4-methylbenzenesulfonyl chloride (2 using basic aqueous media of sodium carbonate. Further, the synthesized compound 3 was reacted with different alkyl/aralkyl halides (4a-j using DMF as aprotic polar solvent and NaH as a base to yield 5a-j compounds. The synthesized molecules were characterized from their spectral data. The synthesized compounds were evaluated against cholinesterase (AChE and BChE, lipoxygenase (LOX, urease, chymotrypsin and tyrosinase enzymes; and found to be the moderate inhibitor against tyrosinase enzyme.

  16. Synthesis and antiplatelet evaluation of novel aryl-sulfonamide derivatives, from natural safrole.

    Lima, L M; Ormelli, C B; Brito, F F; Miranda, A L; Fraga, C A; Barreiro, E J

    1999-06-01

    In the scope of a research program aiming at the synthesis and pharmacological evaluation of novel possible antiplatelet prototype compounds, exploring bioisosterism principles for molecular design, we describe in this paper the synthesis of new aryl-sulfonamides derivatives, structurally similar to known thromboxane A2 receptor antagonists. The synthetic route used to access the new compounds described herein starts from safrole, an abundant Brazilian natural product, which occurs in Sassafras oil (Ocotea pretiosa). The results from preliminary evaluation of these novel aryl-sulfonamide compounds by the platelet aggregation inhibitory test, using rabbit PRP, induced by ADP, collagen, arachidonic acid, and U46619, identified the N-[2-(4-carboxymethoxyphenyl)ethyl]-6-methyl-3,4-methylenedioxyphe nyl- sulfonamido derivative as the most active among them, presenting in IC50 value for the U-46619-induced platelet aggregation in rabbit platelet-rich plasma: 329 microM. PMID:10443173

  17. Inactivation of leukocyte elastase by aryl azolides and sulfonate salts. Structure-activity relationship studies.

    Groutas, W C; Brubaker, M J; Zandler, M E; Mazo-Gray, V; Rude, S A; Crowley, J P; Castrisos, J C; Dunshee, D A; Giri, P K

    1986-07-01

    The inhibitory activity of a series of aryl azolides and sulfonate salts toward human leukocyte elastase is reported. Several of the compounds were found to be potent inhibitors of the enzyme. Active compounds were obtained only when the specificity group and the reactive moiety were separated by a two-carbon chain. The introduction of hydrophobic groups enhanced the inhibitory activity of these compounds, with the exception of the sulfonate salts. The nature of the leaving group had a profound effect on inhibitory activity, with compounds 23 and 26 being the most active (kobsd/[I] = 11,722 and 13,500 M-1 s-1, respectively). PMID:3643283

  18. Synthesis and evaluation of dual antiplatelet activity of bispidine derivatives of N-substituted pyroglutamic acids.

    Misra, Ankita; Anil Kumar, K S; Jain, Manish; Bajaj, Kirti; Shandilya, Shyamali; Srivastava, Smriti; Shukla, Pankaj; Barthwal, Manoj K; Dikshit, Madhu; Dikshit, Dinesh K

    2016-03-01

    N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited both collagen as well as U46619 induced platelet aggregation with concentration dependent anti-platelet efficacy through dual mechanism. In particular, the compound 4j offered significant protection against collagen epinephrine induced pulmonary thromboembolism as well as ferric chloride induced arterial thrombosis, without affecting bleeding tendency in mice. Therefore, the present study suggests that the compound 4j displays a remarkable antithrombotic efficacy much better than aspirin and clopidogrel. PMID:26807542

  19. Synthesis, antimicrobial, and anti-inflammatory activity, of novel S-substituted and N-substituted 5-(1-adamantyl-1,2,4-triazole-3-thiols

    Al-Abdullah ES

    2014-05-01

    Full Text Available Ebtehal S Al-Abdullah,1 Hanadi H Asiri,1 Siham Lahsasni,2 Elsayed E Habib,3 Tarek M Ibrahim,4 Ali A El-Emam1 1Department of Pharmaceutical Chemistry, College of Pharmacy, 2Department of Chemistry, College of Sciences, King Saud University, Riyadh, 3Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Medinah, Saudi Arabia; 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt Abstract: The reaction of 5-(1-adamantyl-4-phenyl-1,2,4-triazoline-3-thione (compound 5 with formaldehyde and 1-substituted piperazines yielded the corresponding N-Mannich bases 6a–f. The reaction of 5-(1-adamantyl-4-methyl-1,2,4-triazoline-3-thione 8 with various 2-aminoethyl chloride yielded separable mixtures of the S-(2-aminoethyl 9a–d and the N-(2-aminoethyl 10a–d derivatives. The reaction of compound 5 with 1-bromo-2-methoxyethane, various aryl methyl halides, and ethyl bromoacetate solely yielded the S-substituted products 11, 12a–d, and 13. The new compounds were tested for activity against a panel of Gram-positive and Gram-negative bacteria and the pathogenic fungus Candida albicans. Compounds 6b, 6c, 6d, 6e, 6f, 10b, 10c, 10d, 12c, 12d, 12e, 13, and 14 displayed potent antibacterial activity. Meanwhile, compounds 13 and 14 produced good dose-dependent anti-inflammatory activity against carrageenan-induced paw edema in rats. Keywords: adamantane derivatives, 1,2,4-triazoles, N-Mannich bases, antimicrobial activity, anti-inflammatory activity

  20. Palladium-catalyzed ?-selective arylation of zincated Boc-allylamines.

    Millet, Anthony; Baudoin, Olivier

    2014-08-01

    The regio- and diastereoselective arylation of Boc-protected allylamines was performed via a one-pot lithiation/transmetalation to zinc/cross-coupling sequence, through an appropriate choice of a phosphine ligand. A variety of ?-arylated products were obtained in moderate to good yield, and the products could be directly transformed into valuable ?-arylamines and ?-aryl aldehydes. PMID:25054519

  1. C-Aryl glucoside SGLT2 inhibitors containing a biphenyl motif as potential anti-diabetic agents.

    Ding, Yuyang; Mao, Liufeng; Xu, Dengfeng; Xie, Hui; Yang, Ling; Xu, Hongjiang; Geng, Wenjun; Gao, Yong; Xia, Chunguang; Zhang, Xiquan; Meng, Qingyi; Wu, Donghai; Zhao, Junling; Hu, Wenhui

    2015-07-15

    A series of highly active C-aryl glucoside SGLT2 inhibitors containing a biphenyl motif were designed and synthesized for biological evaluation. Among the compounds tested, compound 16l demonstrated high inhibitory activity against SGLT2 (IC50=1.9 nM) with an excellent pharmacokinetic profile. Further study indicated that the in vivo efficacy of compound 16l was comparable to that of dapagliflozin, suggesting that further development would be worthwhile. PMID:26026363

  2. Electronic structure and tautomerism of aryl ketones

    Graphical abstract: Photoelectron spectroscopy, tautomerism. - Highlights: • UV photoelectron spectroscopy of aryl ketones. • The relative stability of tautomers and their electronic structures. • The factors influencing tautomerism. - Abstract: The electronic structures of several aryl ketones (AK) and their α-halo derivatives have been studied by UV photoelectron spectroscopy (UPS). The relative stabilities of keto–enol tautomers have been determined using high-level ab initio calculations and the results were used in the analysis of UPS spectra. The main features of electronic structure and tautomerism of the AK derivatives are discussed

  3. Electronic structure and tautomerism of aryl ketones

    Novak, Igor, E-mail: inovak@csu.edu.au [Charles Sturt University, POB 883, Orange, NSW 2800 (Australia); Klasinc, Leo, E-mail: klasinc@irb.hr [Physical Chemistry Department, Ruđer Bošković Institute, HR-10002 Zagreb (Croatia); Šket, Boris, E-mail: Boris.Sket@fkkt.uni-lj.si [Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 (Slovenia); McGlynn, S.P., E-mail: sean.mcglynn@chemgate.chem.lsu.edu [Louisiana State University, Baton Rouge, LA 70803 (United States)

    2015-07-15

    Graphical abstract: Photoelectron spectroscopy, tautomerism. - Highlights: • UV photoelectron spectroscopy of aryl ketones. • The relative stability of tautomers and their electronic structures. • The factors influencing tautomerism. - Abstract: The electronic structures of several aryl ketones (AK) and their α-halo derivatives have been studied by UV photoelectron spectroscopy (UPS). The relative stabilities of keto–enol tautomers have been determined using high-level ab initio calculations and the results were used in the analysis of UPS spectra. The main features of electronic structure and tautomerism of the AK derivatives are discussed.

  4. Nickel-catalyzed three-component domino reactions of aryl Grignard reagents, alkynes, and aryl halides producing tetrasubstituted alkenes.

    Xue, Fei; Zhao, Jin; Hor, T S Andy; Hayashi, Tamio

    2015-03-11

    Three-component reaction of aryl Grignard reagents, alkynes, and aryl halides in the presence of 1 mol % of NiCl2 proceeded sequentially through carbomagnesiation of the alkyne followed by cross-coupling of the resulting alkenyl Grignard reagent with aryl halide to give tetrasubstituted alkenes in high yields. PMID:25714497

  5. Smiles Rearrangement Based Practical One-pot Synthesis of N-Alkyl/aryl-6-aminoquinolines from 6-Hydroxylquinoline

    Xie, Yongsheng; Vijaykumar, B. V. D.; Jang, Kiwan; Choi, Kyungmin; Shin, Dongsoo [Changwon National Univ., Changwon (Korea, Republic of); Zuo, Hua [Southwest Univ., Chongqing (Korea, Republic of); Yoon, Yongjin [Gyeongsang National Univ., Chinju (Korea, Republic of)

    2013-12-15

    The C-N coupling protocol reported herein represents a convenient and practical synthesis of N-alkyl/aryl-6-aminoquinolines in a three-step one-pot manner by simple addition of 6-hydroxyquinoline and N-alkyl/aryl-2-chloroacetamides with Cs{sub 2}CO{sub 3} or K{sub 2}CO{sub 3} in DMF at 150 .deg. C via Smiles rearrangement. An electron donating substituent on the nitrogen counterpart would accelerate the rearrangement process to achieve various anilines in good yields. We currently engaged in making a chemical library including multifarious N-substituted-6-aminoquinolines, to be used in the screening for specific AChEI activity. Furthermore, this work extends the scope of preparing different heterocyclic synthons in drug design for various biological activities. Aminoquinolines and their derivatives are important chemical entities that are widely used as pro-drugs and drugs due to their antimicrobial, cytotoxic and anti-malarial activities etc.

  6. Synthesis of N-substituted phthalimidoalkyl 1,2,3-triazoles via click chemistry

    Moara T. da Silva

    2012-06-01

    Full Text Available In the present work, we have developed a facile procedure for synthesis of new N-phthalimidoalkyl 1H-1,2,3-Triazoles (1-4(a-h using DMF, 10 mol% CuI, Et3N and ultrasound energy at room temperature. This protocol furnished 28 new compounds in 20 to 30 min of reaction and moderate-to-excellent yields (64-94%.

  7. Pseudoephedrine-Directed Asymmetric ?-Arylation of ?-Amino Acid Derivatives.

    Atkinson, Rachel C; Fernndez-Nieto, Fernando; Mas Rosell, Josep; Clayden, Jonathan

    2015-07-27

    Available ?-amino acids undergo arylation at their ??position in an enantioselective manner on treatment with base of N'-aryl urea derivatives ligated to pseudoephedrine as a chiral auxiliary. In?situ silylation and enolization induces diastereoselective migration of the N'-aryl group to the ??position of the amino acid, followed by ring closure to a hydantoin with concomitant explulsion of the recyclable auxiliary. The hydrolysis of the hydantoin products provides derivatives of quaternary amino acids. The arylation avoids the use of heavy-metal additives, and is successful with a range of amino acids and with aryl rings of varying electronic character. PMID:26083236

  8. Synthesis and antimicrobial screening of pyrazolo-3-aryl quinazolin-4(3hones

    Deshmukh M

    2010-01-01

    Full Text Available 2-thio-3-aryl quinazolin-4(3Hone (1 was synthesized by reacting anthranilic acid with thiocarbamate salts of substituted aniline and carbon disulphide, which on reflux with excess of hydrazine hydrate to form 2-hydrazino quinazolin-4(3Hone derivatives (2. The reaction of (2 with variously substituted aryl aldehydes gave the corresponding hydrazones (3. Further, the cyclization of compound (3 in acetic anhydride gave tricyclic pyrazoloquinazolinones (4. All newly synthesized compounds have been tested for their antibacterial activity against gram +ve bacteria B. substilis, S. aureus and gram -ve bacteria E. coli, P. vulgaris. The species used for antifungal activity are Aspergillus niger and Phytophora. Introduction of -OCH3, -OH and -Cl groups to the heterocyclic frame work enhanced antibacterial and antifungal activities.

  9. One-pot synthesis of N-aryl 1,4-dihydropyridine derivatives and their biological activities

    Isaivani Dhinakaran; Vediappen Padmini; Nattamai Bhuvanesh

    2015-12-01

    Highly efficient, one pot synthesis of N-aryl, 1,4-dihydopyridines was carried out by four component reaction. Synthesized 1,4-dihydropyridines were screened for their cytotoxicity against A549 cell line. All the synthesized compounds exhibited better DPPH radical scavenging activity.

  10. Synthesis of novel substituted N-aryl benzamides as hA3G stabilizers and their inhibitory activities against hepatitis C virus replication

    Yanping Li

    2013-09-01

    Full Text Available A series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus (HCV replication in acutely infected Huh7.5 cells. Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities. Compounds 1f, 1g and 4c exhibited potent anti-replicative activity at low micromolar levels (IC50=1.02.0?M with selective indices (SI greater than 40. Mechanistic analysis indicated that the active compounds increased intracellular hA3G protein levels and inhibited HCV replication in a dose-dependent manner. The results demonstrate that this series of substituted N-aryl benzamide compounds warrant further investigation as inhibitors of HCV replication.

  11. Synthesis, Characterization, Thermal and Antimicrobial studies of N-substituted Sulfanilamide derivatives

    Lahtinen, Manu; Kudva, Jyothi; Hegde, Poornima; Bhat, Krishna; Kolehmainen, Erkki; Nonappa; Venkatesh; Naral, Damodara

    2014-02-01

    Four sulfanilamide derivatives N-[4-(phenylsulfamoyl)phenyl]acetamide (1), 4-amino-N-phenylbenzenesulfonamide (2),N-[4-(phenylsulfamoyl)phenyl]benzamide (3) and N-{4-[(3-chlorophenyl)sulfamoyl]phenylbenzamide (4) were synthesized and characterized by Infra-Red (IR), Nuclear Magnetic Resonance (NMR) and UV-visible (UV-Vis) spectra. Also Liquid Chromatographic (LCMS) and High Resolution Mass Spectrometric (HRMS) methods were used. Crystal structures of 1-4 were determined by single crystal X-ray diffraction (XRD) and their conformational and hydrogen bond (HB) network properties were examined with survey of the literature data. Compounds 1 and 2 crystallize in the same orthorhombic Pbca symmetry with equivalent molecular conformation (tilted V-shape) but showed distinct packing and hydrogen bonding models. Compounds 3 and 4 crystallize in monoclinic and triclinic crystal systems, albeit exhibiting identical molecular conformation (L-shaped). Same donor acceptor pairs both on 3 and 4 result to different kind of HB network. Thermogravimetric (TG) and differential scanning calorimetric (DSC) methods were used to evaluate thermal properties of the substances. All sulfanilamide derivatives have melting points between195-227 °C, initiation of thermal decomposition between 259-271 °C and enthalpies of fusion ΔHfusT = 38.96, 36.60, 46.23 and 44.81 kJ mol-1 were determined for 1-4, respectively. The derivatives were screened for their antibacterial and antifungal activities against various bacterial and fungal strains. It is observed that there is no significant antibacterial activity with the introduction of the benzene ring to CO-NH group or SO2-NH moiety, and none of the compounds exhibited antifungal activity.

  12. QSAR Studies on N-aryl Derivative Activity Towards Alzheimer’s Disease

    Kamalakaran Anand Solomon; Veluchamy Abirami; Srinivasan Sundararajan

    2009-01-01

    A Quantitative Structure Activity Relationship (QSAR) study has been an attempted on a series of 88 N-aryl derivatives which display varied inhibitory activity towards both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), targets in Alzheimer’s drug discovery. QSAR models were derived for 53 and 61 compounds for each target, respectively, with the aid of genetic function approximation (GFA) technique using topological, molecular shape, electronic and structural descriptors. The p...

  13. Preparation of Peptide p-Nitroanilides using an Aryl Hydrazine Solid Support

    Kwon, Y; Welsh, K; Mitchell, A R; Camarero, J A

    2004-08-05

    Peptide p-nitroanilides are useful compounds for studying protease activity, however the poor nucleophilicity of p-nitroaniline makes their preparation difficult. We describe a new efficient approach for the Fmoc-based synthesis of peptide p-nitroanilides using an aryl hydrazine resin. Mild oxidation of the peptide hydrazide resin yields a highly reactive acyl diazene, which efficiently reacts with weak nucleophiles. We have prepared several peptide p-nitroanilides, including substrates for the Lethal Factor protease from B. anthracis.

  14. Polymeric media comprising polybenzimidazoles N-substituted with organic-inorganic hybrid moiety

    Klaehn, John R [Idaho Falls, ID; Peterson, Eric S [Idaho Falls, ID; Wertsching, Alan K [Idaho Falls, ID; Orme, Christopher J [Shelley, ID; Luther, Thomas A [Idaho Falls, ID; Jones, Michael G [Pocatello, ID

    2009-12-15

    A PBI compound includes imidazole nitrogens at least a portion of which are substituted with an organic-inorganic hybrid moiety may be included in a separator medium. At least 85% of the imidazole nitrogens may be substituted. The organic-inorganic hybrid moiety may be an organosilane moiety, for example, (R)Me.sub.2SiCH.sub.2-- where R is selected from among methyl, phenyl, vinyl, and allyl. The separatory medium may exhibit an H.sub.2, Ar, N.sub.2, O.sub.2, CH.sub.3, or CO.sub.2 gas permeability greater than the gas permeability of a comparable separatory medium comprising the PBI compound without substitution. The separatory medium may further include an electronically conductive medium and/or ionically conductive medium. The separatory medium may be used as a membrane (semi-permeable, permeable, and non-permeable), a barrier, an ion exhcange media, a filter, a gas chromatography coating (such as stationary phase coating in affinity chromatography), etc.

  15. Aryl Polyphosphonates: Useful Halogen-Free Flame Retardants for Polymers

    Li Chen

    2010-10-01

    Full Text Available Aryl polyphosphonates (ArPPN have been demonstrated to function in wide applications as flame retardants for different polymer materials, including thermosets, polycarbonate, polyesters and polyamides, particularly due to their satisfactory thermal stability compared to aliphatic flame retardants, and to their desirable flow behavior observed during the processing of polymeric materials. This paper provides a brief overview of the main developments in ArPPN and their derivatives for flame-retarding polymeric materials, primarily based on the authors’ research work and the literature published over the last two decades. The synthetic chemistry of these compounds is discussed along with their thermal stabilities and flame-retardant properties. The possible mechanisms of ArPPN and their derivatives containing hetero elements, which exhibit a synergistic effect with phosphorus, are also discussed.

  16. Highly efficient and mild copper-catalyzed N- and C-arylations with aryl bromides and iodides.

    Cristau, Henri-Jean; Cellier, Pascal P; Spindler, Jean-Francis; Taillefer, Marc

    2004-11-01

    Mild, efficient, copper-catalyzed N-arylation procedures for nitrogen heterocycles, amides, carbamates, and C-arylation procedures for malonic acid derivatives have been developed that afford high yields of arylated products with excellent selectivity. The N-arylation of imidazole with aryl bromides or iodides was found to be greatly accelerated by inexpensive, air-stable catalyst systems, combining catalytic copper salts or oxides with a set of structurally simple chelating ligands. The reaction was shown to be compatible with a broad range of aryl halides, encompassing sterically hindered, electron-poor, and electron-rich ones, providing the arylated products under particularly mild conditions (50-82 degrees C). The lower limit in ligand and catalyst loading and the scope of Ullmann-type condensations catalyzed by complexes bearing those ligands with respect to the nucleophile class have also been investigated. Chelating Schiff base Chxn-Py-Al (1c) generates a remarkably general copper catalyst for N-arylation of pyrrole, indole, 1,2,4-triazole, amides, and carbamates; and C-arylation of diethyl malonate, ethyl cyanoacetate, and malononitrile with aryl iodides under mild conditions (50-82 degrees C). The new method reported here is the most successful to date with regard to Ullmann-type arylation of some of these nucleophiles. PMID:15457520

  17. Naphthalene bisimides asymmetrically and symmetrically N-substituted with triarylamine--comparison of spectroscopic, electrochemical, electronic and self-assembly properties.

    Rybakiewicz, Renata; Zapala, Joanna; Djurado, David; Nowakowski, Robert; Toman, Petr; Pfleger, Jiri; Verilhac, Jean-Marie; Zagorska, Malgorzata; Pron, Adam

    2013-02-01

    Two semiconducting naphthalene bisimides were comparatively studied: NBI-(TAA)(2), symmetrically N-substituted with triaryl amine and asymmetric NBI-TAA-Oc with triaryl amine and octyl N-substituents. Both compounds show very similar spectroscopic and redox properties but differ in their supramolecular organization. As evidenced by STM, in monolayers on HOPG they form ordered 2D structures, however of different packing patterns. NBI-(TAA)(2) does not form ordered 3D structures, yielding amorphous thin films whereas films of NBI-TAA-Oc are highly crystalline. DFT calculations predict the ionization potential (IP) of 5.22 eV and 5.18 eV for NBI-TAA-Oc and NBI-(TAA)(2), respectively, as well as the electron affinity values (EA) of -3.25 eV and -3.22 eV. These results are consistent with the cyclic voltammetry data which yield similar values of IP (5.20 eV and 5.19 eV) and somehow different values of EA (-3.80 eV and -3.83 eV). As judged from these data, both semiconductors should exhibit ambipolar behavior. Indeed, NBI-TAA-Oc is ambipolar, showing hole and electron mobilities of 4.5 × 10(-5) cm(2)/(V s) and of 2.6 × 10(-4) cm(2)/(V s), respectively, in the field effect transistor configuration. NBI-(TAA)(2) is not ambipolar and yields field effect only in the p-channel configuration. This different behavior is rationalized on the basis of structural factors. PMID:23243662

  18. Electrospun N-Substituted Polyurethane Membranes with Self-Healing Ability for Self-Cleaning and Oil/Water Separation.

    Fang, Wenyuan; Liu, Libin; Li, Ting; Dang, Zhao; Qiao, Congde; Xu, Jinku; Wang, Yanyan

    2016-01-18

    Membranes with special functionalities, such as self-cleaning, especially those for oil/water separation, have attracted much attention due to their wide applications. However, they are difficult to recycle and reuse after being damaged. Herein, we put forward a new N-substituted polyurethane membrane concept with self-healing ability to address this challenge. The membrane obtained by electrospinning has a self-cleaning surface with an excellent self-healing ability. Importantly, by tuning the membrane composition, the membrane exhibits different wettability for effective separation of oil/water mixtures and water-in-oil emulsions, whilst still displaying a self-healing ability and durability against damage. To the best of our knowledge, this is the first report to demonstrate a self-healing membrane for oil/water separation, which provides the fundamental research for the development of advanced oil/water separation materials. PMID:26603820

  19. Living Polymerization of N -Substituted β-Alanine N -Carboxyanhydrides: Kinetic Investigations and Preparation of an Amphiphilic Block Copoly-β-Peptoid

    Grossmann, Arlett

    2012-07-03

    Poly(α-peptoid)s (N-substituted polyglycines) are interesting peptidomimetic biomaterials that have been discussed for many applications. Poly(β-peptoid)s (N-substituted poly-β-alanines), although equally intriguing, have received much less attention. Here we present results that suggest that while N-substituted β-alanine N-carboxyanhydrides can undergo a living nucleophilic ring-opening polymerization, the solubility of poly(β-peptoid)s can be very poor, which contributes to the limited accessibility using other synthetic approaches. The living character of the polymerization was utilized for the preparation of the first polymerized amphiphilic block copoly-β-peptoid. Our results may open a new route towards highly defined functional poly(β-peptoid)s which could represent biomaterials. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Visible-light-driven Photocatalytic N-arylation of Imidazole Derivatives and Arylboronic Acids on Cu/graphene catalyst

    Cui, Yan-Li; Guo, Xiao-Ning; Wang, Ying-Yong; Guo, Xiang-Yun

    2015-07-01

    N-aryl imidazoles play an important role as structural and functional units in many natural products and biologically active compounds. Herein, we report a photocatalytic route for the C-N cross-coupling reactions over a Cu/graphene catalyst, which can effectively catalyze N-arylation of imidazole and phenylboronic acid, and achieve a turnover frequency of 25.4 h-1 at 25 oC and the irradiation of visible light. The enhanced catalytic activity of the Cu/graphene under the light irradiation results from the localized surface plasmon resonance of copper nanoparticles. The Cu/graphene photocatalyst has a general applicability for photocatalytic C-N, C-O and C-S cross-coupling of arylboronic acids with imidazoles, phenols and thiophenols. This study provides a green photocatalytic route for the production of N-aryl imidazoles.

  1. Study of configuration and conformational analysis of 2-aryl-trans- decahydroquinolin-4-ols by mass spectrometric approach

    Sharmila, N.; Hari Babu, B.

    2016-04-01

    The conformational analysis of 2-Aryl-trans-decahydroquinolin-4-ols was studied by using electron ionization mass spectrometry. The peak intensities, that is the abundance of the peaks and ion mass, characteristics of each fragmentation were used as the principle tools for determining the conformations. An examination of the Mass fragmentation indicated that the configuration of the hydroxyl group of 2-aryl-trans-decahydroquinolin-4-ols was equatorial and axial configuration. In 3-Methyl-2-aryl-trans-decahydroquinolin-4-ols the methyl and phenyl groups had equatorial configuration. In 1-Methyl-2-aryl-trans-decahydroquinolin-4-ol and 1,3-dimethyl-2-aryl-trans-decahydroquinolin-4-ol the N-methyl group has greater preference for equatorial position. It was found that in all the epimeric molecules the base peak was formed only after the elimination of cyclohexyl ring except in 1-Methyl epimeric molecules. Further, in all the spectra of the epimeric compounds the peaks up to stable tropylium cation were studied.

  2. Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates

    Ackerman, Laura K. G.; Lovell, Matthew M.; Weix, Daniel J.

    2015-08-01

    The advent of transition-metal catalysed strategies for forming new carbon-carbon bonds has revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules. In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation of two distinct catalysts--multimetallic catalysis--can be used instead. Many important reactions rely on multimetallic catalysis, such as the Wacker oxidation of olefins and the Sonogashira coupling of alkynes with aryl halides, but this approach has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing oxidative addition. Here, we demonstrate that cooperativity between two group 10 metal catalysts--(bipyridine)nickel and (1,3-bis(diphenylphosphino)propane)palladium--enables a general cross-Ullmann reaction (the cross-coupling of two different aryl electrophiles). Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple carbon-hydrogen bonds that is required for direct arylation methods. Selectivity can be achieved without an excess of either substrate and originates from the orthogonal reactivity of the two catalysts and the relative stability of the two arylmetal intermediates. While (1,3-bis(diphenylphosphino)propane)palladium reacts preferentially with aryl triflates to afford a persistent intermediate, (bipyridine)nickel reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5 per cent cross-coupled product in isolation, together they are able to achieve a yield of up to 94 per cent. Our results reveal a new method for the synthesis of biaryls, heteroaryls, and dienes, as well as a general mechanism for the selective transfer of ligands between two metal catalysts. We anticipate that this reaction will simplify the synthesis of pharmaceuticals, many of which are currently made with pre-formed organometallic reagents, and lead to the discovery of new multimetallic reactions.

  3. N-SUBSTITUTION AND 1-ADRENERGIC RECEPTOR AFFINITY OF LAUDANOSINE ANALOGUES

    PATRICIO ITURRIAGA-VSQUEZ

    2006-09-01

    Full Text Available Benzyltetrahydroisoquinoline (BTHIQ molecules are able to adopt widely differing conformations that depend on the presence or absence of N-substituents. To assess the possible role of BTHIQ conformation on the affinity of these compounds for a 1-adrenergic receptors, of interest for the management of hypertension, the racemic N-unsubstituted BTHIQ norlaudanosine and a series of N-alkylated derivatives were assessed for binding to rat brain cortical sites labelled with the radioligand [H]prazosin. The a 1-adrenergic affinity in this series increased with the bulk of the substituent on the nitrogen atom, from the N-ethyl to the N-propyl analogue. Comparison of these results with published data for related BTHIQs and for the rigid mimics of the fully extended and semi-folded conformations of laudanosine, tetrahydropalmatine and glaucine, suggested that the a 1-adrenergic receptor binding site is able to accommodate either conformation. The presence of a bulky substituent on the nitrogen atom seems to favor receptor binding independently of the favored conformation, and that the orientation in which BTHIQs are bound probably differs depending on the presence or absence of a hydroxyl group at a key position

  4. Cloning and heterologous expression of two aryl-aldehyde dehydrogenases from the white-rot basidiomycete Phanerochaete chrysosporium

    Nakamura, Tomofumi [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Fukuoka Institute of Health and Environmental Sciences, 39 Mukaizano, Dazaifu-shi, Fukuoka 818-0135 (Japan); Ichinose, Hirofumi [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Wariishi, Hiroyuki, E-mail: hirowari@agr.kyushu-u.ac.jp [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Bio-Architecture Center, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)

    2010-04-09

    We identified two aryl-aldehyde dehydrogenase proteins (PcALDH1 and PcALDH2) from the white-rot basidiomycete Phanerochaete chrysosporium. Both PcALDHs were translationally up-regulated in response to exogenous addition of vanillin, one of the key aromatic compounds in the pathway of lignin degradation by basidiomycetes. To clarify the catalytic functions of PcALDHs, we isolated full-length cDNAs encoding these proteins and heterologously expressed the recombinant enzymes using a pET/Escherichia coli system. The open reading frames of both PcALDH1 and PcALDH2 consisted of 1503 nucleotides. The deduced amino acid sequences of both proteins showed high homologies with aryl-aldehyde dehydrogenases from other organisms and contained ten conserved domains of ALDHs. Moreover, a novel glycine-rich motif 'GxGxxxG' was located at the NAD{sup +}-binding site. The recombinant PcALDHs catalyzed dehydrogenation reactions of several aryl-aldehyde compounds, including vanillin, to their corresponding aromatic acids. These results strongly suggested that PcALDHs metabolize aryl-aldehyde compounds generated during fungal degradation of lignin and various aromatic xenobiotics.

  5. Synthesis of N-substituted Cyclic Hydrocarbons, such as Pyrimidine, in The Ionosphere of Titan

    Bera, P. P.; Peverati, R.; Head-Gordon, M.; Lee, T. J.

    2014-12-01

    The instruments on board the CASSINI spacecraft observed large carbonaceous molecules in the upper atmosphere of Titan. How these large polyatomic molecules are synthesized in such exotic conditions is, thus far, unknown. Molecular ions, including positive and negative ions, are in relative abundance in the ionosphere of Titan. Hence, barrierless ion-molecule interactions may play a major role in guiding molecules towards each other and initiating reactions. We study these condensation pathways to determine whether they are a viable means of forming large pure hydrocarbon molecules, and nitrogen-containing carbonaceous chains, stacks, and even cyclic compounds. By employing accurate quantum chemical methods we have investigated the processes of growth, structures, nature of bonding, mechanisms, and spectroscopic properties of the ensuing ionic products after pairing small carbon, hydrogen, and nitrogen-containing molecules with major ions observed in the upper atmosphere of Titan, e.g. C2H5+ and HCNH+. We have also studied the ion-neutral association pathways involving pure-carbon molecules e.g. acetylene, ethylene and other hydrocarbons, and their dissociation fragments in a plasma discharge. We have investigated how nitrogen atoms are incorporated into the carbon ring during growth. Specifically, we explored the mechanisms by which the synthesis of pyrimidine will be feasible in the atmosphere of Titan in conjunction with ion-mobility experiments. We have used accurate ab initio coupled cluster theory, Møller-Plesset perturbation theory, density functional theory, and coupled cluster theory quantum chemical methods together with large correlation consistent basis sets in these investigations. We found that a series of hydrocarbons with a specific stoichiometric composition prefers cyclic molecule formation rather than chains. Some of the association products we investigated have large oscillator strengths for charge-transfer type electronic excitations in the near infrared and visible regions of the electromagnetic spectrum. Our quantum chemistry computations complement well the results from the molecular/ion plasma experiments performed by the Laboratory Astrochemistry groups at Ames.

  6. C(aryl-O Bond Formation from Aryl Methanesulfonates via Consecutive Deprotection and SNAr Reactions with Aryl Halides in an Ionic Liquid

    Yang Chen

    2007-04-01

    Full Text Available An efficient K3PO4-mediated synthesis of unsymmetrical diaryl ethers using the ionic liquid [Bmim]BF4 (1-butyl-3-methylimidazolium tetrafluoroborate as solvent has been developed. The procedure involves consecutive deprotection of aryl methane-sulfonates and a nucleophilic aromatic substitution (SNAr with activated aryl halides.

  7. Copper-catalysed N-arylation of arylsulfonamides with aryl bromides and aryl iodides using KF/Al2O3

    Rahman Hosseinzadeh; Mahmood Tajbakhsh; Maryam Mohadjerani; Mohammad Alikarami

    2010-03-01

    An efficient synthesis of -arylsulfonamides with a variety of aryl bromides, aryl iodides and heteroaryl bromides using KF/Al2O3 as a suitable base, CuI as an inexpensive catalyst and ,'-dimethylethylenediamine (,'-DMEDA) as an effective ligand is described.

  8. Formation Routes For Pure and N-substituted Cyclic Hydrocarbon Molecules in The Ionosphere of Titan

    Bera, P. P.; Peverati, R.; Head-Gordon, M.; Lee, T. J.

    2013-12-01

    Titan's upper atmosphere contains large carbonaceous molecules as has been observed by the instruments on board the CASSINI spacecraft. How these large polyatomic molecules are synthesized in such exotic conditions is, thus far, unknown. Molecular ions are in relative abundance in the ionosphere of Titan. Hence, barrierless ion-molecule interactions may play a major role in guiding molecules towards each other and initiating reactions. We study these cold condensation pathways to determine whether they are a viable means of forming large pure hydrocarbon molecules, and nitrogen-containing carbonaceous chains, stacks, and even cyclic compounds. By employing accurate quantum chemical methods we have investigated the processes of growth, structures, nature of bonding, mechanisms, and spectroscopic properties of the ensuing ionic products after pairing small carbon, hydrogen, and nitrogen-containing molecules with major ions observed in the upper atmosphere of Titan, e.g. C2H5+ and HCNH+. We have also studied the ion-neutral association pathways involving pure-carbon molecules e.g. acetylene, ethylene and other hydrocarbons, and their dissociation fragments in a plasma discharge. Additionally, we have investigated how nitrogen atoms are incorporated into the carbon ring during growth. We have used accurate ab initio coupled cluster theory, Møller-Plesset perturbation theory and density functional theory quantum chemical methods together with large correlation consistent basis sets in these investigations. We also employed time-dependent density functional theory and equations-of-motion coupled cluster theory to compute electronic excitation energies and oscillator strengths of the products of the ion-molecule reactions. We obtained accurate vibrational frequencies under the harmonic approximation and vibrational intensities using the double harmonic approximation for fundamental molecular vibrations. We identified three types of bonding motifs with strong, moderate, and weak binding energies among the carbonaceous complexes. Both linear and cyclic isomers identified on the potential energy surface of these molecular complexes are expected to form rather easily due to electrostatic interactions. We uncovered that a series of hydrocarbons with a specific stoichiometric composition prefers cyclic molecule formation rather than chains. Some of the association products we investigated have large oscillator strengths for charge-transfer type electronic excitations in the near infrared and visible regions of the electromagnetic spectrum. Our quantum chemistry computations complement well the results from the molecular/ion plasma experiments performed by the Laboratory Astrochemistry groups at Ames. P. P. Bera, Martin Head-Gordon, and Timothy J. Lee Astron & Astrophys. 535, A74, (2011) P. P. Bera, M. Head-Gordon, and T. J. Lee, 15, 2012-2023,Phys. Chem. Chem. Phys. (2013) P. P. Bera, Roberto Peverati, M. Head-Gordon, and Timothy J. Lee, To be submitted (2013)

  9. Aryl Hydrocarbon Receptor Control of Adaptive Immunity

    Quintana, Francisco J.; Sherr, David H

    2013-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that belongs to the family of basic helix-loop-helix transcription factors. Although the AhR was initially recognized as the receptor mediating the pathologic effects of dioxins and other pollutants, the activation of AhR by endogenous and environmental factors has important physiologic effects, including the regulation of the immune response. Thus, the AhR provides a molecular pathway through which environmental f...

  10. Novel 3-aryl indoles as progesterone receptor antagonists for uterine fibroids.

    Richardson, Timothy I; Clarke, Christian A; Yu, Kuo-Long; Yee, Ying K; Bleisch, Thomas J; Lopez, Jose E; Jones, Scott A; Hughes, Norman E; Muehl, Brian S; Lugar, Charles W; Moore, Terry L; Shetler, Pamela K; Zink, Richard W; Osborne, John J; Montrose-Rafizadeh, Chahrzad; Patel, Nita; Geiser, Andrew G; Galvin, Rachelle J Sells; Dodge, Jeffrey A

    2011-02-10

    We report the synthesis and characterization of novel 3-aryl indoles as potent and efficacious progesterone receptor (PR) antagonists with potential for the treatment of uterine fibroids. These compounds demonstrated excellent selectivity over other steroid nuclear hormone receptors such as the mineralocorticoid receptor (MR). They were prepared from 2-bromo-6-nitro indole in four to six steps using a Suzuki cross-coupling as the key step. Compound 8f was orally active in the complement 3 model of progesterone antagonism in the rat uterus and demonstrated partial antagonism in the McPhail model of progesterone activity. PMID:24900294

  11. Synthesis of aryl b-N-acetylglucosamine desmodified at C-6 as potential antimicrobial agents

    We report herein the synthesis of aryl beta-N-acetylglucosaminides containing azido, amino and acetamido groups at C-6 as potential antimicrobial agents. It was expected that these compounds could interfere with the biosynthesis and/or biotransformation of Nacetylglucosamine in fungi and bacteria. None of the compounds showed antimicrobial activity against bacteria (Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa), filamentous fungus (Aspergillus niger) and yeasts (Saccharomyces cerevisae, Candida albicans and Candida tropicallis), at the concentration of 1 mg/mL in agar diffusion assay. (author)

  12. Infrared study of lignin: Reexamination of aryl-alkyl ether C-O stretching peak assignments

    Infrared (IR) C-O ether stretching peak assignments of beta- O-4 interunit bonds and methoxyl groups have been assigned by isotope labeling. The Caryl-O peak for both types of ethers was typically found at 1262-1224 cm-1, but syringyl and 3,5-dimethoxyl derivatives gave Caryl-O peaks of 1328-1295 cm-1 and 1254-1204 cm-1. The Caryl-O peak for all ethers was found at 1047-1004 cm-1. These assignments are similar to values reported in general IR tables for aryl-alkyl ethers, except for the unusually high Caryl-O stretch for syringyl and 3,5- dimethoxyl compounds. IR shift tables also often list a peak at 1176 cm-1 associated with the Caryl-O bond of aryl-alkyl ethers. It is doubtful the peaks observed in this region are due to the Caryl-O bond

  13. N-dealkylation of arylpiperazine derivatives: disposition and metabolism of the 1-aryl-piperazines formed.

    Caccia, Silvio

    2007-08-01

    In recent years several arylpiperazine derivatives have reached the stage of clinical application, mainly for the treatment of depression, psychosis or anxiety. Examples are the pyrimidinylpiperazine buspirone, the chlorophenylpiperazine derivatives nefazodone and trazodone, the dichlorophenylpiperazine aripiprazole and the benzisothiazolyl derivatives perospirone and ziprasidone. Most of them undergo extensive pre-systemic and systemic metabolism including CYP3A4-dependent N-dealkylation to 1-aryl-piperazines. These metabolites are best known for the variety of serotonin receptor-related effects they cause in man and animals, although some have affinity for other neurotransmitter receptors; others, however, are still largely unexplored despite uncontrolled use as amphetamine-like designer drugs. Once formed they distribute extensively in tissues, including brain which is the target site of most arylpiperazine derivatives, and are then primarily biotransformed by CYP2D6-dependent oxidation to hydroxylates which are excreted as conjugates; only 1-(2-benzisothiazolyl)-piperazine is more susceptible to sulfur oxidation than to aromatic hydroxylation. In studies analysing animal brain and human blood, 1-aryl-piperazine concentrations were either higher or lower than the parent compound(s), although information is available only for some derivatives. At steady state, the metabolite-to-parent drug ratios varied widely among individuals taking the same dosage of the same arylpiperazine derivative. This is consistent with the known individual variability in the expression and activity of CYP3A4 and CYP2D6. This review also surveys current published information on physiological and pathological factors affecting the 1-aryl-piperazine-to-parent drug ratios and examines the potential role of 1-aryl-piperazine formation in the pharmacological actions of the arylpiperazine derivatives that are already or will shortly be available in major markets. PMID:17691920

  14. N-Heterocyclic carbenepalladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

    Ismail zdemir

    2013-02-01

    Full Text Available New PdNHC complexes have been synthesized and employed for palladium-catalyzed direct arylation of pyrrole derivatives by using electron-deficient aryl chlorides as coupling partners. The desired coupling products were obtained in moderate to good yields by using 1 mol % of these air-stable palladium complexes. This is an advantage compared to the procedures employing air-sensitive phosphines, which have been previously shown to promote the coupling of aryl chlorides with heteroarenes.

  15. Synthesis and antiinflammatory activity of n-aryl anthranilic acid and its derivatives

    Joshi J

    2007-01-01

    Full Text Available N-aryl anthranilic acid and its derivatives (3a-f have been synthesized via Ullmann condensation of o-chloro benzoic acid with various substituted anilines (2a-f in the presence of cupric oxide and anhydrous potassium carbonate. All the synthesized compounds (3a-f were characterized by mp, TLC, UV, IR, 1 H NMR and mass spectral analysis. All the synthesized compounds (3a-f were screened for their antiinflammatory activity by carrageenan induced rat paw edema method. All the synthesized compounds (3a-f showed significant antiinflammatory activity. Compounds 3a and 3c were found to be the most potent compounds.

  16. In-Silico Identification and Molecular docking studies of Qui nolone resistance determining region (QRDR of e.coli DNA Gyrase-a with n- substituted Piperazinyl Schiff bases of Gatifloxacin

    Sahu Susanta Kumar

    2013-12-01

    Full Text Available A series of N-substituted piperazinyl Schiff bases of gatifloxacin were designed and were docked within the “Quinolone Resistance Determining Region” (QRDR of E. coli DNA Gyrase-A (EcGyr-A chain (QRDR-A, to evaluate the possible relationship between docking scores and their contribution to biological activity, along with the interaction with target residues. The obtained docking scores of analogues were compared with score of reference ligand gatifloxacin, under identical experimental sets. The analogue with 2-(pyridin-4-ylcarbonyl hydrazinylidenesubstituents, 1h showed highest docking score (-167.66 kcal.mol-1. Compounds with substituents 2-hydroxyimino, 1b and2-carbamothioylhydrazinylidene, 1d showed moderate docking score (-161.32 kcal.mol-1 and -158.64 kcal.mol-1respectively against QRDR-A. Among the eight analogues selected for docking studies, a moderate correlation was also observed between docking scores and experimental biological activity reported in our previouswork. Further structural analysis of docking studies on our compounds suggests attractive starting point to find new lead compounds with potential improvements.

  17. Electrochemical and Physical properties of N-substituted arylmethylene pyrrole polymers and N-alkylmethine pyrrole copolymers

    Highlights: N-Arylmethylene and methine pyrroles were electropolymerised into polymers and copolymers. N-arylmethylene pyrrole monomers readily formed stable homopyrrole polymer films. N-alkylmethine pyrrole monomers only formed stable copolymers films with pyrrole. N-(1,2-dicarboxyethyl)-1H-pyrrole films readily complexed Cu+ or Cd2+ ions under a appliedve field. -- Abstract: The electrochemical behaviour of N-arylmethylene and N-alkylmethine pyrrole monomers were investigated in their ability to be electropolymerised into polymer and co-polymer films with pyrrole using the techniques of cyclic voltammetry and scanning electron microscopy (SEM). N-substituted arylmethylene pyrrole monomers readily formed homopolymers by the oxidative electropolymerisation of pyrrole monomers by potentiostatic cycling in acetonitrile containing tetrabutylammonium perchlorate. The polymer films formed were brown in appearance and redox active, with the exception of the 1-((4-chlorophenyl)methyl)-1H-pyrrole (1d) which formed a pale yellow film lacking redox activity. The thickness of films produced calculated on the charge consumed followed the order 1e + and Cd2+ ions at a concentration of 1 10?4 M under an appliedve field and to release the metal ion on stepping the potential to zero

  18. Palladium-Catalyzed, tert-Butyllithium-Mediated Dimerization of Aryl Halides and Its Application in the Atropselective Total Synthesis of Mastigophorene?A.

    Buter, Jeffrey; Heijnen, Dorus; Vila, Carlos; Hornillos, Valentn; Otten, Edwin; Giannerini, Massimo; Minnaard, Adriaan J; Feringa, Ben L

    2016-03-01

    A palladium-catalyzed direct synthesis of symmetric biaryl compounds from aryl halides in the presence of tBuLi is described. In?situ lithium-halogen exchange generates the corresponding aryl lithium reagent, which undergoes a homocoupling reaction with a second molecule of the aryl halide in the presence of the palladium catalyst (1?mol?%). The reaction takes place at room temperature, is fast (1?h), and affords the corresponding biaryl compounds in good to excellent yields. The application of the method is demonstrated in an efficient asymmetric total synthesis of mastigophorene?A. The chiral biaryl axis is constructed with an atropselectivity of 9:1 owing to catalyst-induced remote point-to-axial chirality transfer. PMID:26878822

  19. Mechanism-based inactivation of benzo[a]pyrene hydroxylase by aryl acetylenes and aryl olefins

    A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo[a]pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo[a]pyrene hydroxylase. The mechanism-based loss of benzo[a]pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenes therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, 3H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo[a]pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne

  20. Selective copper catalysed aromatic N-arylation in water

    Engel-Andreasen, Jens; Shimpukade, Bharat; Ulven, Trond.

    2013-01-01

    4,7-Dipyrrolidinyl-1,10-phenanthroline (DPPhen) was identified as an efficient ligand for copper catalyzed selective arom. N-arylation in water. N-Arylation of indoles, imidazoles and purines proceeds with moderate to excellent yields and complete selectivity over aliph. amines. Aq. medium and th...

  1. Aryl (meth)acrylates and polymers based on them

    Data on the synthesis, polymerisation and copolymerisation of aryl (meth)acrylates are generalised and systematised. Chemical and photochemical properties of the polymers and copolymers are considered. Basic directions of practical application of poly[aryl (meth)acrylates] and copolymers are demonstrated. The bibliography includes 449 references.

  2. Palladium-Catalyzed alpha-Arylation of Tetramic Acids

    Storgaard, Morten; Dorwald, F. Z.; Peschke, B.; Tanner, David Ackland

    2009-01-01

    A mild, racemization-free, palladium-Catalyzed alpha-arylation of tetramic acids (2,4-pyrrolidinediones) has been developed. Various amino acid-derived tetramic acids were cleanly arylated by treatment with 2 mol % of Pd(OAc)(2), 4 mol % of a sterically demanding biaryl phosphine, 2.3 equiv of K2...

  3. Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates.

    Ackerman, Laura K G; Lovell, Matthew M; Weix, Daniel J

    2015-08-27

    The advent of transition-metal catalysed strategies for forming new carbon-carbon bonds has revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules. In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation of two distinct catalysts--multimetallic catalysis--can be used instead. Many important reactions rely on multimetallic catalysis, such as the Wacker oxidation of olefins and the Sonogashira coupling of alkynes with aryl halides, but this approach has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing oxidative addition. Here, we demonstrate that cooperativity between two group 10 metal catalysts--(bipyridine)nickel and (1,3-bis(diphenylphosphino)propane)palladium--enables a general cross-Ullmann reaction (the cross-coupling of two different aryl electrophiles). Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple carbon-hydrogen bonds that is required for direct arylation methods. Selectivity can be achieved without an excess of either substrate and originates from the orthogonal reactivity of the two catalysts and the relative stability of the two arylmetal intermediates. While (1,3-bis(diphenylphosphino)propane)palladium reacts preferentially with aryl triflates to afford a persistent intermediate, (bipyridine)nickel reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5 per cent cross-coupled product in isolation, together they are able to achieve a yield of up to 94 per cent. Our results reveal a new method for the synthesis of biaryls, heteroaryls, and dienes, as well as a general mechanism for the selective transfer of ligands between two metal catalysts. We anticipate that this reaction will simplify the synthesis of pharmaceuticals, many of which are currently made with pre-formed organometallic reagents, and lead to the discovery of new multimetallic reactions. PMID:26280337

  4. Synthesis, Half-Wave Potentials and Antiproliferative Activity of 1-Aryl-substituted Aminoisoquinolinequinones

    Juana Andrea Ibacache

    2014-01-01

    Full Text Available The synthesis of a variety of 1-aryl-7-phenylaminoisoquinolinequinones from 1,4-benzoquinone and arylaldehydes via the respective 1-arylisoquinolinequinones is reported. The cyclic voltammograms of the new compounds exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasi-reversible oxidation peaks. The half-wave potential values (EI½ of the members of the series have proven sensitive to the electron-donor effect of the aryl group (phenyl, 2-thienyl, 2-furyl at the 1-position as well as to the phenylamino groups (anilino, p-anisidino at the 7-position. The antiproliferative activity of the new compounds was evaluated in vitro using the MTT colorimetric method against one normal cell line (MRC-5 lung fibroblasts and two human cancer cell lines: AGS human gastric adenocarcinoma and HL-60 human promyelocytic leukemia cells in 72-h drug exposure assays. Among the series, compounds 5a, 5b, 5g, 5h, 6a and 6d exhibited interesting antiproliferative activities against human gastric adenocarcinoma. The 1-arylisoquinolinequinone 6a was found to be the most promising active compound against the tested cancer cell lines in terms of IC50 values (1.19; 1.24 µM and selectivity index (IS: 3.08; 2.96, respect to the anti-cancer agent etoposide used as reference (IS: 0.57; 0.14.

  5. An efficient and convenient synthesis of N-substituted amides under heterogeneous condition using Al(HSO4)3 via Ritter reaction

    Elnaz Karimian; Batool Akhlaghinia; Sara S E Ghodsinia

    2016-03-01

    An efficient and inexpensive synthesis of N-substituted amides from the reaction of aliphatic and aromatic nitriles with various benzylic alcohols (secondary and tertiary) and tert-butyl alcohol by refluxing nitromethane via the Ritter reaction catalyzed by aluminum hydrogen sulfate [Al(HSO4)3] is described. Thecatalyst which is an air-stable, cost-effective solid acid could be readily recycled by filtration and reused four times without any significant loss of its activity.

  6. The optical properties, synthesis and characterization of novel 5-aryl-3-benzimidazolyl-1-phenyl-pyrazoline derivatives

    Cao, Xiao Qun; Lin, Xiao Hui; Zhu, Yan; Ge, Yan Qing; Wang, Jian Wu

    2012-12-01

    A series of novel 5-aryl-3-benzimidazolyl-1-phenyl-pyrazoline derivatives were synthesized by the reaction of benzimidazolyl chalcone and phenylhydrazine in 41-72% yields. The compounds were characterized using IR, 1H NMR and HRMS. Absorption and fluorescence spectra were measured in different organic solvent. An intense absorption maxima was noted at ca. 370 nm and emission maxima was noted at ca. 460 nm. The absorption spectra of the pyrazoline derivatives reveal that 5-aryl group attached to the pyrazoline ring hardly influenced the maximum absorption. The fluorescence spectra of these compounds indicated the emission wavelength was red shifted and the fluorescence intensity was decreased with the increase in solvent polarity.

  7. Synthesis and Antiviral Bioactivities of 2-Aryl- or 2-Methyl-3-(substituted- Benzalamino-4(3H-quinazolinone Derivatives

    Zhuo Chen

    2007-12-01

    Full Text Available A simple and general method has been developed for the synthesis of various4(3H-quinazolinone derivatives by the treatment of the appropriate 3-amino-2-aryl-4(3H-quinazolinone with a substituted benzaldehyde in ethanol. The structures of the compoundswere characterized by elemental analysis, IR, 1H-NMR and 13C-NMR spectra. The title 2-aryl- or 2-methyl-3-(substituted-benzalamino-4(3H-quinazolinone compounds III-1~III-31 were found to possess moderate to good antiviral activity. Semi-quantitative PCR andReal Time PCR assays were used to ascertain the target of action of compound III-31against TMV. The studies suggest that III-31 possesses antiviral activity due to inductionof up-regulation of PR-1a and PR-5, thereby inhibiting virus proliferation and movementby enhancement of the activity of some defensive enzyme.

  8. Synthesis and antimicrobial activities of new oxime carbamates of 3-aryl-2-thioquinazolin-4(3H)-one

    Suresh S Patil; Swati D Jadhav; M B Deshmukh

    2012-09-01

    S-alkylation of 3-aryl-2-thioquinazolin-4(3H)-one (1) with chloroacetone gave 2-(propanonyl thio)-3-arylquinazol-4(3H)ones (2). Further, the treatment of compound (2) with hydroxylamine hydrochloride gave the corresponding oximes (3) which on reaction with phenyl isocyanate in THF yielded corresponding oxime carbamates 4. The synthesized compounds have been confirmed using IR and 1H NMR, mass spectral data together with elemental analysis. All newly synthesized compounds have been tested for their antibacterial and antifungal activities.

  9. Consecutive Three-Component Synthesis of 3-(HeteroAryl-1H-pyrazoles with Propynal Diethylacetal as a Three-Carbon Building Block

    Thomas J. J. Mller

    2011-11-01

    Full Text Available A novel consecutive three-component synthesis of 3-(heteroaryl-1H-pyrazoles via room temperature Sonogashira arylation of propynal diethylacetal used as a propargyl aldehyde synthetic equivalent has been disclosed. The final acetal cleavage-cyclocondensation with hydrazine hydrochloride at 80 C rapidly furnishes the title compounds in a one-pot fashion.

  10. Synthesis and biological evaluation of novel tetrahydroisoquinoline-C-aryl glucosides as SGLT2 inhibitors for the treatment of type 2 diabetes.

    Pan, Xuan; Huan, Yi; Shen, Zhufang; Liu, Zhanzhu

    2016-05-23

    A series of novel tetrahydroisoquinoline-C-aryl glucosides has been synthesized and evaluated for the inhibition of human SGLT2. Compared with dapagliflozin, compound 13h exhibited equivalent in vitro inhibitory activity against SGLT2, which might become a promising candidate for the treatment of type 2 diabetes. PMID:26974378

  11. Synthesis of 5-Dialkyl(aryl)aminomethyl-8-hydroxyquinoline Dansylates as Selective Fluorescent Sensors for Fe3+

    Yaowu Sha; Feng Wang; Ruogu Peng

    2007-01-01

    A series of 5-dialkyl(aryl)aminomethyl-8-hydroxyquinoline dansylates were synthesized and their fluoroionophoric properties toward representative alkali ions, alkaline earth ions and transition metal ions were investigated. Among the selected ions, Fe3+ caused considerable quenching of the fluorescence, while Cr3+ caused quenching to some extent. The absence of any significant fluorescence quenching effects of the other ions examined, especially Fe2+, renders these compounds highly useful Fe3...

  12. Synthesis of Novel 1-[(2,6-Dichloro-4-trifluoromethyl)phenyl]-3-aryl-1H-pyrazole-4-carbaldehydes

    Anjiang Zhang; Lisheng Ding; Changhua Ge; Huanan Hu

    2010-01-01

    A series of novel 1-[(2,6-dichloro-4-trifluoromethyl)phenyl]-3-aryl-1H-pyrazole-4-carbaldehydes 6a-i were synthesized using the Vilsmeier-Haack reagent. The structures of all the title compounds have been confirmed by elemental analysis, 1H-NMR and 13C-NMR and in addition, the structure of intermediate 5b was investigated by X-ray crystallography.

  13. A new one-pot synthesis of 1,2,4-oxadiazoles from aryl nitriles, hydroxylamine and crotonoyl chloride

    Masoumeh Zakeri; Majid M Heravi; Ebrahim Abouzari-Lotf

    2013-07-01

    The reaction of aryl nitriles with hydroxylamine using acetic acid as a catalyst followed by subsequent addition of crotonoyl chloride to the intermediate amidoxime represents a straightforward one-pot access to new 1,2,4-oxadiazole synthesis under mild conditions. The course of the reaction was found to be high yielding and all new compounds were well characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS) and elemental analysis.

  14. Glucosides with cyclic diarylpolynoid as novel C-aryl glucoside SGLT2 inhibitors.

    Kang, Suk Youn; Kim, Min Ju; Lee, Jun Sung; Lee, Jinhwa

    2011-06-15

    Novel C-aryl glucoside SGLT2 inhibitors containing cyclic diarylpolynoid motif were designed and synthesized for biological evaluation. Alkylzinc bromides have been efficiently prepared by the direct insertion of zinc metal into alkyl bromides. The organozinc reagents underwent smooth Pd-catalyzed cross-coupling reactions. Subsequent ring closing metathesis using 2nd generation Grubbs catalyst successfully generated novel class of ansa-compounds. These glucosides with cyclic diarylpolynoids demonstrated moderate in vitro inhibitory activity against SGLT2 in this series to date (IC(50)=59.5-103 nM). PMID:21592794

  15. Syntheses and Pharmacological Evaluations of Novel N-substituted Bicyclo-heptan-2-amines at NMDA Receptors

    Ates-Alagoz, Zeynep; Sun, Shengguo; Wallach, Jason; Adejare, Adeboye

    2011-01-01

    Several novel norcamphor (bicycloheptane) based compounds were designed and synthesized as noncompetitive NMDA receptor antagonists at the Phencyclidine (PCP) binding sites. The heterocyclic ring was also varied to examine piperidine, pyrrolidine and morpholine groups. We examined pharmacological activities of these compounds in vitro (binding studies) and in vivo (MES test). Pharmacological evaluations revealed one of the compounds, 5a, to be a good lead, exhibiting moderate binding at NMDA ...

  16. Cloning, expression and characterization of an aryl-alcohol dehydrogenase from the white-rot fungus Phanerochaete chrysosporium strain BKM-F-1767

    Yang Dong-Dong

    2012-06-01

    Full Text Available Abstract Background The white-rot fungus Phanerochaete chrysosporium is among the small group of fungi that can degrade lignin to carbon dioxide while leaving the crystalline cellulose untouched. The efficient lignin oxidation system of this fungus requires cyclic redox reactions involving the reduction of aryl-aldehydes to the corresponding alcohols by aryl-alcohol dehydrogenase. However, the biochemical properties of this enzyme have not been extensively studied. These are of most interest for the design of metabolic engineering/synthetic biology strategies in the field of biotechnological applications of this enzyme. Results We report here the cloning of an aryl-alcohol dehydrogenase cDNA from the white-rot fungus Phanerochaete chrysosporium, its expression in Escherichia coli and the biochemical characterization of the encoded GST and His6 tagged protein. The purified recombinant enzyme showed optimal activity at 37°C and at pH 6.4 for the reduction of aryl- and linear aldehydes with NADPH as coenzyme. NADH could also be the electron donor, while having a higher Km (220 μM compared to that of NADPH (39 μM. The purified recombinant enzyme was found to be active in the reduction of more than 20 different aryl- and linear aldehydes showing highest specificity for mono- and dimethoxylated Benzaldehyde at positions 3, 4, 3,4 and 3,5. The enzyme was also capable of oxidizing aryl-alcohols with NADP + at 30°C and an optimum pH of 10.3 but with 15 to 100-fold lower catalytic efficiency than for the reduction reaction. Conclusions In this work, we have characterized the biochemical properties of an aryl-alcohol dehydrogenase from the white-rot fungus Phanerochaete chrysosporium. We show that this enzyme functions in the reductive sense under physiological conditions and that it displays relatively large substrate specificity with highest activity towards the natural compound Veratraldehyde.

  17. Highly Efficient C-SeCF3 Coupling of Aryl Iodides Enabled by an Air-Stable Dinuclear Pd(I) Catalyst.

    Aufiero, Marialuisa; Sperger, Theresa; Tsang, Althea S-K; Schoenebeck, Franziska

    2015-08-24

    Building on our recent disclosure of catalysis at dinuclear Pd(I) sites, we herein report the application of this concept to the realization of the first catalytic method to convert aryl iodides into the corresponding ArSeCF3 compounds. Highly efficient C-SeCF3 coupling of a range of aryl iodides was achieved, enabled by an air-, moisture-, and thermally stable dinuclear Pd(I) catalyst. The novel SeCF3 -bridged dinuclear Pd(I) complex 3 was isolated, studied for its catalytic competence and shown to be recoverable. Experimental and computational data are presented in support of dinuclear Pd(I) catalysis. PMID:26118426

  18. Multicomponent, solvent-free synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[]-xanthen-11-one derivatives catalysed by cyanuric chloride

    Zhan-Hui Zhang; Peng Zhang; Shu-Hong Yang; Hong-Juan Wang; Jia Deng

    2010-05-01

    An efficient and direct protocol for the preparation of 12-aryl-8,9,10,12-tetrahydro-benzo[] xanthen-11-one derivatives employing a three-component one-pot reaction of aryl aldehydes, 2-naphthol and cyclic 1,3-dicarbonyl compounds in the presence of a catalytic amount of cyanuric chloride (2,4,6-trichloro-1,3,5-triazine, TCT) under solvent-free conditions is described. The desired products are obtained in high yields with short reaction times.

  19. Boronated porphyrin compounds

    Kahl, Stephen B. (Portola Valley, CA); Koo, Myoung-Seo (San Francisco, CA)

    1992-01-01

    A compound is described having the structure ##STR1## where R preferably is ##STR2## and most preferably R.sup.3 is a closo-carborane and R.sup.2 is --H, an alkyl or aryl having 1 to about 7 carbon atoms, This invention was made with Government support under NIH Grant No. CA-37961 awarded by the Department of Health and Human Services and under the Associated Universities Inc. Contract No. De-AC02-76CH00016 with the U.S. Department of Energy. The Government has rights in this invention.

  20. The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

    Volodymyr V. Tkachenko

    2014-12-01

    Full Text Available The switchable three-component reactions of 5-amino-3-methylisoxazole, salicylaldehyde and N-aryl-3-oxobutanamides under different conditions were studied and discussed. The unexpected influence of the aryl substituent in N-aryl-3-oxobutanamides on the behavior of the reaction was discovered. The key influence of ultrasonication and Lewis acid catalysts led to an established protocol to selectively obtain two or three types of heterocyclic scaffolds depending on the substituent in the N-aryl moiety.

  1. Synthesis and Biological evaluation of some of N-alkylidine/ Arylidene-5-Alkyl/Aryl - 1, 3, 4-Thiadiazol- 2 -Amines

    Agarwal Alka

    2013-03-01

    Full Text Available A series N-Alkylidine/Arylidene-5- Alkyl/Aryl-1, 3, 4- Thiadiazol-2-Amines have been synthesized via multistep reaction sequence. The 5-alkyl/aryl-1, 3, 4-thiadiazol-2- amine derivatives were prepared by the reaction of different aliphatic/ aromatic carboxylic acids with thiosemicarbazide in presence of catalytic amount of concentrated sulfuric acid. These derivatives were treated with different aldehydes and ketones to afford the titled compounds. Structures of synthesized compounds were assigned on the basis analytical and spectral data. All the synthesized compounds were subjected to preliminary in-vitro antibacterial activity against Gram-positive bacterial strains Bacillus Subtillis and Gram-negative bacterial strains Klebsiella Pneumoniae, Escheria coli and Pseudomonas aeruginasa. The antifungal activity of the synthesized derivatives was evaluated against Candida albicans and Aspergillus fumigates. The synthesized compounds were found to possess comparable antimicrobial activity to the standard drug.

  2. Azo-hydrazone tautomerism of aryl azo pyridone dyes

    Mirković Jelena M.

    2013-01-01

    Full Text Available In the last three or four decades disperse dyes derived from pyridones (in particular azo pyridone dyes have gained in importance, and are widely used in various fields. These compounds have excellent coloration properties, and are suitable for the dyeing of polyester fabrics. Basic features of these dyes are simplicity of their synthesis by diazotation and azo coupling. They generally have high molar extinction coefficient with medium to high light and wet fastness. The absorption maxima of these dyes show their visible absorption wavelength ranging from yellow to orange, which can be attributed to poorly delocalized electrons in the pyridone ring. However, there are several dyes with deep colors such as red or violet. Pyridone dyes with alkyl and aryl groups in ortho position to azo group show 2-pyridone/2-hydroxypyridine tautomerism, while those containing OH and NHR groups conjugated with the azo group show azo-hydrazone tautomerism. Determining azo-hydrazone tautomerism could be therefore interesting, since the tautomers have different physico-chemical properties and most importantly different coloration. The literature on azo-hydrazone tautomerism, determination of equilibrium position, and investigation of substituent and solvent influence on tautomerism has been summarized in the presented review. The general conclusion is that the equilibrium between two tautomers is influenced by the structure of the compounds and by the solvents used. The tautomeric behavior patterns of the arylazo pyridone dyes in the reviewed literature has been studied using various instrumental techniques, including FT-IR, UV-vis, and NMR spectroscopy. The quantum chemical calculations related to the azo-hydrazon tautomerism have also been included. A large number of pyridone dyes exist in hydrazone form in solid state, while in solvents there is a mixture of tautomers. In addition, the X-ray single-crystal diffraction data analysis of some commercial pyridone dyes has been discussed concluding that they all crystallize in the hydrazone form.

  3. Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B.

    Verma, Neelam; Mittal, Minakshi; Verma, Raman Kumar

    2008-01-01

    Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors. PMID:19238234

  4. A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

    Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca2+ channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca2+ channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca2+ channel-blocking activity and antioxidant properties. The Ca2+ channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca2+ channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca2+ channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca2+ entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca2+ blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca2+ blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties

  5. Palladium-catalyzed asymmetric reductive heck reaction of aryl halides.

    Yue, Guizhou; Lei, Kaining; Hirao, Hajime; Zhou, Jianrong Steve

    2015-05-26

    Asymmetric reductive Heck reaction of aryl halides is realized in high stereoselectivity. Hydrogen-bond donors, trialkylammonium salts in a glycol solvent, were used to promote halide dissociation from neutral arylpalladium complexes to access cationic, stereoselective pathways. PMID:25867113

  6. SYNTHESIS AND ANTIMICROBIAL EVALUATION OF 2-(4-FLUORO BENZYLTHIO)-N-(SUBSTITUTED PHENYL)PYRIMIDINE-4-AMINES

    N.M. Goudgaon*, Y. Rohini Reddy and B.U. Sheshikant

    2013-01-01

    Reaction of 4-fluorobenzylchloride with 2-thiouracil (1) gave 2-(4-fluorobenzylthio)pyrimidin-4(3H)-one (2), which on chlorination with POCl3 furnished 4-chloro-2-(4-fluorobenzylthio)-4-chloropyrimidine (3). This intermediate when treated with various substituted anilines gave desired targeted compounds 4(a-k) in 50-90% yield. Structural assignments of the synthesized compounds were based on their IR, 1H NMR, Mass and analytical data. The antimicrobial evaluation of newly synthesized compound...

  7. Induction of targeted osteogenesis with 3-aryl-2H-benzopyrans and 3-aryl-3H-benzopyrans: Novel osteogenic agents.

    Gupta, Atul; Ahmad, Imran; Kureel, Jyoti; Hasanain, Mohammad; Pandey, Praveen; Singh, Sarita; John, Aijaz A; Sarkar, Jayanta; Singh, Divya

    2016-04-01

    Development of target oriented chemotherapeutics for treatment of chronic diseases have been considered as an important approach in drug development. Following this approach, in our efforts for exploration of new osteogenic leads, substituted 3-aryl-2H-benzopyran and 3-aryl-3H-benzopyran derivatives (19, 20a-e, 21, 22a-e, 26, 27, 28a-e, 29, 31a-b, 32 and 33) have been characterized as estrogen receptor-β selective osteogenic (bone forming) agents. The synthesized compounds were evaluated for osteogenic activity using mouse calvarial osteoblast cells. Four compounds viz20b, 22a, 27and 32 showed significant osteogenic activity at EC50 values 1.35, 34.5, 407 and 29.5pM respectively. Out of these, 20b and 32 were analyzed for their bone mineralization efficacy and osteogenic gene expression by qPCR. The results showed that 20b and 32 significantly increased mineral nodule formation and the transcript levels of BMP-2, RUNX-2 and osteocalcin at 100pM concentrations respectively. Further mechanistic studies of 20b and 32 using transiently knocked down expression of ER-α and β in mouse osteoblast (MOBs) showed that 20b and 32 exerts osteogenic efficacy via activation of estrogen receptor-β preferentially. Additionally, compounds showed significant anticancer activity in a panel of cancer cell lines within the range of (IC50) 6.54-27.79μM. The most active molecule, 22b inhibited proliferation of cells by inducing apoptosis and arresting cell cycle at sub-G0 phase with concomitant decrease in cells at S phase. PMID:26807865

  8. Development of N-substituted quinolinimides, as potential PET tracers for the visualisation of δ-opioid receptors

    In order to develop radiotracers for in vivo studies of δ-opioid receptors by Positron Emission Tomography (PET) or Single Photon Emission computed Tomography (SPECT), we undertook the synthesis of halogenated analogues (chlorinated and brominated) of compound 12. These analogues were prepared by a convergent synthesis and from these novel structures a halogen exchange reaction has been performed to complete this series. These molecules were tested to determine their in vitro affinity and selectivity toward δ opioid receptors. The compounds 12 and 15 were labelled with carbon-11. The radiosynthesis of compound 12, in weak radioactivity chemistry, was performed first by the Stille reaction and second by a new methodology based on the transfer reaction of [11C]-methyl group. This new methodology used a mono-organotin compound prepared by addition of [11C]-iodomethane onto Lappert's stannylene. The compound [11C]-12 was obtained with 60 and 10% radiochemical yield respectively. In order to produce higher radioactivity quantities, the Stille reaction was automated. The compounds [11C]-12 and [11C]-15 were obtained in 40 minutes with a specific radioactivity ranging from 322 to 747 mCi/μmol. (author)

  9. A convenient catalyst system for microwave accelerated cross-coupling of a range of aryl boronic acids with aryl chlorides

    Milton Edward J

    2007-05-01

    Full Text Available Abstract A convenient microwave accelerated cross-coupling procedure between aryl chlorides with a range of boronic acids has been developed. An explanation for the low reactivity of highly fluorinated boronic acids in Suzuki coupling is provided.

  10. N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties

    Ondrej Jandourek

    2014-01-01

    Full Text Available In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction times. The products of this reaction were characterized by IR, NMR and other analytical data. The compounds were evaluated for their antibacterial, antifungal and herbicidal activity. Compounds 3 (R = 3,4-Cl, 9 (R = 2-Cl and 11 (R = 4-CF3 showed good antimycobacterial activity against Mycobacterium tuberculosis (MIC = 6.25 µg/mL. It was found that the lipophilicity is important for antimycobacterial activity and the best substitution on the benzyl moiety of the compounds is a halogen or trifluoromethyl group according to Craig’s plot. The activities against bacteria or fungi were insignificant. The presented compounds also inhibited photosynthetic electron transport in spinach chloroplasts and the IC50 values of the active compounds varied in the range from 16.4 to 487.0 µmol/L. The most active substances were 2 (R = 3-CF3, 3 (R = 3,4-Cl and 11 (R = 4-CF3. A linear dependence between lipophilicity and herbicidal activity was observed.

  11. C-aryl glucosides substituted at the 4'-position as potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes.

    Xu, Baihua; Feng, Yan; Cheng, Huawei; Song, Yanli; Lv, Binhua; Wu, Yuelin; Wang, Congna; Li, Shengbin; Xu, Min; Du, Jiyan; Peng, Kun; Dong, Jiajia; Zhang, Wenbin; Zhang, Ting; Zhu, Liangcheng; Ding, Haifeng; Sheng, Zelin; Welihinda, Ajith; Roberge, Jacques Y; Seed, Brian; Chen, Yuanwei

    2011-08-01

    A series of C-aryl glucosides with various substituents at the 4'-position of the distal aryl ring have been synthesized and evaluated for inhibition of hSGLT1 and hSGLT2. Introduction of alkyl or alkoxy substituents at the 4'-position was found to improve SGLT2 potency, whereas introduction of a hydrophilic group at this position was deleterious. Compounds with alkoxy-, cycloalkoxy- or cycloalkenyloxy-ethoxy scaffolds exhibited good inhibitory activity and high selectivity toward SGLT2. Selected compounds were investigated for in vivo efficacy. PMID:21737266

  12. Compounds of thiourea and its complexes with metal salts

    A review of literature on thiourea compounds is given. Three types of the compounds are described: clathrates, ion complexes and coordination compounds. The main attention is paid to thiourea complexes of transition metals. The structure of the complexes is considered, using X-ray structural analysis and other physicochemical methods. Stability and lability of thiourea coordination compounds and its N- and N, N'-substituted derivatives are characterized, as well as peculiarities of the given ligands in substitution reactions. Acid-basic, redox and thermal properties of thioamide complexes are discussed

  13. MICROWAVE ASSISTED SYNTHESIS OF 3-(2-BENZOYL-6-HYDROXY-3-METHYL BENZO[b] FURAN-5-YL-5-(ARYL-4, 5-DIHYDRO-1H-PYRAZOLE CARBOTHIOAMIDES AND THEIR ANTIBACTERIAL ACTIVITY Mikrowellen unterstützte Synthese von 3 - (2-Benzoyl-6-HYDROXY-3-METHYL Benzo [b] furan-5-yl -5 - (ARYL -4, 5-DIHYDRO-1H-pyrazol CARBOTHIOAMIDES UND ihre antibakterielle Aktivität

    Ashok D, Sudershan K,Khalilullah M

    2011-10-01

    Full Text Available A series of 3-(2-Benzoyl-6-hydroxy-3-methyl benzo[b] furan-5-yl-5-(aryl-4, 5-dihydro-1Hpyrazole carbothioamides have been prepared by the reaction of (E-1-(2-Benzoyl-6-hydroxy-3- methylbenzo[b]furan-5-yl-3-aryl-2-propen-1-ones with thiosemicarbazide in the presence of sodium hydroxide under microwave irradiation. The structures of newly synthesized compounds have been confirmed on the basis of elemental analysis, IR,1H-NMR,13C-NMR and mass spectral data. All the compounds were screened for their antibacterial activity.

  14. Synthesis of aryl-1H-1,2,3-triazoles via 1,3-dipolar cycloaddition

    Wagner O. Valena

    2012-06-01

    Full Text Available A series of Aryl-1H-1,2,3-triazoles were prepared from the reaction between aril-azide (1 with 1.5 equiv. of terminal alkynes (2a-o. The reactions carried out at room temperature and in the presence of CuI (10 mol% in acetonitrile. The compounds (3a-o were obtained in moderate-to-good yields (50-94%. In general, not was observed significant inductive effect on the reactivity of the alkynes (2a-f. The alcohol alkynes (2i-k showed moderate yields 50-72%. On the other hand, the reaction with alkyl alkynes (2m,n furnished the compounds (3m and (3n in excellent yields of 89% and 90%, respectively.

  15. Synthesis, activity evaluation, and docking analysis of barbituric acid aryl hydrazone derivatives as RSK2 inhibitors.

    Xue, Mengzhu; Xu, Minghao; Lu, Weiqiang; Huang, Jin; Li, Honglin; Xu, Yufang; Liu, Xiaofeng; Zhao, Zhenjiang

    2013-08-01

    The 90 kDa ribosomal S6 kinases (RSKs), especially RSK2, have attracted attention for the development of new anticancer agents. Through structural optimization of the hit compound 1 from our previous study, a series of barbituric acid aryl hydrazone analogues were designed and synthesized as potential RSK2 inhibitors. The most potent one, compound 9, showed a higher activity against RSK2 with an IC50 value of 1.95 μM. To analyze and elucidate their structure-activity relationship, the homology model of RSK2 N-terminal kinase domain was built and molecular docking simulations were performed, which provide helpful clues to design new inhibitors with desired activities. PMID:22545939

  16. The use of AgNO3/BF3.Et2O and HNO3/Al(H2PO43 systems in the synthesis of aryl thiosulfonates

    Edson Anjos Santos

    2012-06-01

    Full Text Available The thiosulfonates are a class of compounds of great industrial importance. It is worth noting that the aryl thiosulfonates present several biological activities. The synthesis of these compounds is known in the literature although; only a few make use of thiols as the sole starting material. This work shows the use of two reaction systems employed for the synthesis of nitrophenols, AgNO3/BF3.EtO2 (I and HNO3/Al(H2PO43 (II, as an alternative to the preparation of aryl thiosulfonates. The use of system I led to higher yields (72-76% then system II (56-61%. These methodologies have not been reported before for the synthesis of these compounds and the products were obtained with good purity.

  17. Discovery of potent cytotoxic ortho-aryl chalcones as new scaffold targeting tubulin and mitosis with affinity-based fluorescence.

    Zhu, Cuige; Zuo, Yinglin; Wang, Ruimin; Liang, Baoxia; Yue, Xin; Wen, Gesi; Shang, Nana; Huang, Lei; Chen, Yu; Du, Jun; Bu, Xianzhang

    2014-08-14

    A series of new ortho-aryl chalcones have been designed and synthesized. Many of these compounds were found to exhibit significant antiproliferation activity toward a panel of cancer cell lines. Selected compounds show potent cytotoxicity against several drug resistant cell lines including paclitaxel (Taxol) resistant human ovarian carcinoma cells, vincristine resistant human ileocecum carcinoma cells, and doxorubicin resistant human breast carcinoma cells. Further investigation revealed that active analogues could inhibit the microtubule polymerization by binding to colchicine site and thus induce multipolar mitosis, G2/M phase arrest, and apoptosis of cancer cells. Furthermore, affinity-based fluorescence enhancement was observed during the binding of active compounds with tubulin, which greatly facilitated the determination of tubulin binding site of the compounds. Finally, selected compound 26 was found to exhibit obvious in vivo antitumor activity in A549 tumor xenografts model. Our systematic studies implied a new scaffold targeting tubulin and mitosis for novel antitumor drug discovery. PMID:25061803

  18. Chromatin remodeling by curcumin alters endogenous aryl hydrocarbon receptor signaling.

    Mohammadi-Bardbori, Afshin; Akbarizadeh, Amin Reza; Delju, Fatemeh; Rannug, Agneta

    2016-05-25

    The aim of this study was to gain more information about the mechanisms that regulate expression of the aryl hydrocarbon receptor (AHR) target gene CYP1A1. Human hepatoma cells (HepG2 and Huh7) and human immortalized keratinocytes (HaCaT) were treated with different concentrations of the dietary polyphenolic compound curcumin (CUR) alone or in combination with the natural AHR agonist 6-formylindolo[3,2-b]carbazole (FICZ). In an earlier study, we described that CUR can activate the AHR indirectly by inhibiting metabolic clearance of FICZ. Here, we measured cell viability, activation of AHR signaling, oxidative stress and histone modifying activities in response to CUR at concentrations ranging from 0.1 to 50 μM. We observed apparent non-linear responses on cell viability and activation of AHR signaling. The CYP1A1 expression and the CYP1A1 enzyme activity in the presence of CUR reflected the histone acetylation efficiency observed in nuclear extracts. At the lowest concentration, CUR significantly decreased histone deacetylase activity and increased the FICZ-induced CYP1A1 activity. In contrast, at the highest concentration, CUR increased the formation of reactive oxygen species, significantly inhibited histone acetylation, and temporally decreased FICZ-induced CYP1A1 activity. The results suggest that CUR can both increase and decrease the accessibility of DNA and thereby influence transcriptional responses to the ligand-activated AHR. This suggestion was supported by the fact that chromatin remodeling treatments with trichostatin A, p300, or 5-aza-dC increased CYP1A1 transcription. We conclude that the AHR-dependent transcriptional efficiency is modified by factors that influence the cellular redox status and the chromatin structure. PMID:27041069

  19. Toxicity of teriflunomide in aryl hydrocarbon receptor deficient mice.

    Redaelli, Chiara; Gaffarogullari, Ece Cazibe; Brune, Maik; Pilz, Caroline; Becker, Simon; Sonner, Jana; Jschke, Andres; Grne, Hermann-Josef; Wick, Wolfgang; Platten, Michael; Lanz, Tobias Volker

    2015-12-01

    The intracellular transcription factor aryl hydrocarbon receptor (AHR) is bound and activated by xenobiotics, thereby promoting their catabolism by inducing expression of cytochrome P450 oxidase (CYP) genes through binding xenobiotic response elements (XRE) in their promoter region. In addition, it is involved in several cellular pathways like cell proliferation, differentiation, regeneration, tumor invasiveness and immune responses. Several pharmaceutical compounds like benzimidazoles activate the AHR and induce their own metabolic degradation. Using newly generated XRE-reporter mice, which allow in vivo bioluminescence imaging of AHR activation, we show here that the AHR is activated in vivo by teriflunomide (TER), which has recently been approved for the treatment of multiple sclerosis. While we did not find any evidence that the AHR mediates the immunomodulatory effects of TER, AHR activation led to metabolism and detoxification of teriflunomide, most likely via CYP. Mice deficient for the AHR show higher blood levels of teriflunomide, suffer from enhanced thrombo- and leukopenia and elevated liver enzymes as well as from severe gastrointestinal ulcers and bleeding which are lethal after 8-11 days of treatment. Leukopenia, acute liver damage and diarrhea have also been described as common side effects in human trials with TER. These data suggest that the AHR is relevant for detoxification not only of environmental toxins but also of drugs in clinical use, with potential implications for the application of AHR-modifying therapies in conjunction to TER in humans. The XRE-reporter mouse is a useful novel tool for monitoring AHR activation using in vivo imaging. PMID:26341389

  20. Theoretical study on the electronic structures and phosphorescent properties of a series of iridium(III) complexes with the different positional N-substitution in the pyridyl moiety

    The geometry structures, electronic structures, absorption and phosphorescent properties of a series of iridium(III) complexes with the different N-substitution cyclometalating ligand and the same benzyldiphenylphosphine auxiliary ligand have been theoretically investigated by using the density functional theory method. The lowest energy absorption wavelengths are located at 378 nm for A, 430 nm for B, 411 nm for C, 436 nm for D, and 394 nm for E. The introduction of N atom substitution at 1-, 2-, 3-, and 4-positions on the pyridyl moiety of complex A leads to an obvious redshifted absorption. The lowest energy emissions for complexes AE are localized at 450, 409, 438, 483, and 429 nm, respectively, simulated in CH2Cl2 medium at M052X level. Ionization potential and electron affinity have been calculated to evaluate the injection abilities of holes and electrons into these complexes. For complex C, the calculated results showed that it can possibly possess the larger radiative decay rate (kr) value than those of other four complexes. It is anticipated that the theoretical studies can provide valuable information for designing new phosphorescent metal complexes of organic light-emitting diodes. - Highlights: Five Ir(III) complexes have been theoretically investigated. The effect of N-substitution cyclometalating ligand has been studied. The complex C possibly possesses the largest radiative decay rate value

  1. Theoretical study on the electronic structures and phosphorescent properties of a series of iridium(III) complexes with the different positional N-substitution in the pyridyl moiety

    Han, Deming; Hao, Fengqi [School of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022 (China); Tian, Jian [Clean Energy Technology Laboratory, Changchun University of Science and Technology, Changchun 130022 (China); Pang, Chunying; Li, Jingmei [School of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022 (China); Zhao, Lihui, E-mail: zhaolihui@yahoo.com [School of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022 (China); Zhang, Gang [State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China)

    2015-03-15

    The geometry structures, electronic structures, absorption and phosphorescent properties of a series of iridium(III) complexes with the different N-substitution cyclometalating ligand and the same benzyldiphenylphosphine auxiliary ligand have been theoretically investigated by using the density functional theory method. The lowest energy absorption wavelengths are located at 378 nm for A, 430 nm for B, 411 nm for C, 436 nm for D, and 394 nm for E. The introduction of N atom substitution at 1-, 2-, 3-, and 4-positions on the pyridyl moiety of complex A leads to an obvious redshifted absorption. The lowest energy emissions for complexes A–E are localized at 450, 409, 438, 483, and 429 nm, respectively, simulated in CH{sub 2}Cl{sub 2} medium at M052X level. Ionization potential and electron affinity have been calculated to evaluate the injection abilities of holes and electrons into these complexes. For complex C, the calculated results showed that it can possibly possess the larger radiative decay rate (k{sub r}) value than those of other four complexes. It is anticipated that the theoretical studies can provide valuable information for designing new phosphorescent metal complexes of organic light-emitting diodes. - Highlights: • Five Ir(III) complexes have been theoretically investigated. • The effect of N-substitution cyclometalating ligand has been studied. • The complex C possibly possesses the largest radiative decay rate value.

  2. Synthesis, structure elucidation, DNA-PK and PI3K and anti-cancer activity of 8- and 6-aryl-substituted-1-3-benzoxazines.

    Morrison, Rick; Al-Rawi, Jasim M A; Jennings, Ian G; Thompson, Philip E; Angove, Michael J

    2016-03-01

    The synthesis of 6-aryl, 8- aryl, and 8-aryl-6-chloro-2-morpholino-1,3-benzoxazines with potent activity against PI3K and DNA-PK is described. Synthesis of thirty one analogues was facilitated by an improved synthesis of 3-bromo-2-hydroxybenzoic acid 13 by de-sulphonation of 3-bromo-2-hydroxy-5-sulfobenzoic acid 12 en route to 2-methylthio-substituted-benzoxazine intermediates 17-19. From this series, compound 20k (LTURM34) (dibenzo[b,d]thiophen-4-yl) (IC50=0.034?M) was identified as a specific DNA-PK inhibitor, 170 fold more selective for DNA-PK activity compared to PI3K activity. Other compounds of the series show markedly altered selectivity for various PI3K isoforms including compound 20i (8-(naphthalen-1-yl) a potent and quite selective PI3K? inhibitor (IC50=0.64?M). Finally, nine compounds were evaluated and showed antiproliferative activity against an NCI panel of cancer cell lines. Compound 20i (8-(naphthalen-1-yl) showed strong anti-proliferative activity against A498 renal cancer cells that warrants further investigation. PMID:26854431

  3. Kinetics and Mechanism of Pyridinolyses of Aryl Methyl and Aryl Propyl Chlorothiophosphates in Acetonitrile

    The nucleophilic substitution reactions of Y-aryl methyl (8) and Y-aryl propyl (10) chlorothiophosphates with X-pyridines are studied kinetically in acetonitrile at 35.0 .deg. C. The Hammett and Bronsted plots with X in the nucleophiles for both substrates exhibit biphasic concave upwards with a break region between X = 3-Me and H. The obtained values of the cross-interaction constants (?XY) are negative with 8 while positive with 10 despite the same free energy correlations with X for both substrates. A stepwise mechanism with a rate-limiting bond formation is proposed with 8, whereas a stepwise mechanism with a rate-limiting leaving group departure from the intermediate is proposed with 10 based on the sign of ?XY, negative and positive with 8 and 10, respectively. A frontside nucleophilic attack is proposed with strongly basic pyridines based on the considerably great magnitudes of ?X and ?X values while a backside attack is proposed with weakly basic pyridines based on the relatively small magnitudes of ?X and ?X for both substrates

  4. Control of Reactivity and Regioselectivity for On-Surface Dehydrogenative Aryl-Aryl Bond Formation.

    Kocić, Nemanja; Liu, Xunshan; Chen, Songjie; Decurtins, Silvio; Krejčí, Ondřej; Jelínek, Pavel; Repp, Jascha; Liu, Shi-Xia

    2016-05-01

    Regioselectivity is of fundamental importance in chemical synthesis. Although many concepts for site-selective reactions are well established for solution chemistry, it is not a priori clear whether they can easily be transferred to reactions taking place on a metal surface. A metal will fix the chemical potential of the electrons and perturb the electronic states of the reactants because of hybridization. Additionally, techniques to characterize chemical reactions in solution are generally not applicable to on-surface reactions. Only recent developments in resolving chemical structures by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) paved the way for identifying individual reaction products on surfaces. Here we exploit a combined STM/AFM technique to demonstrate the on-surface formation of complex molecular architectures built up from a heteroaromatic precursor, the tetracyclic pyrazino[2,3-f][4,7]phenanthroline (pap) molecule. Selective intermolecular aryl-aryl coupling via dehydrogenative C-H activation occurs on Au(111) upon thermal annealing under ultrahigh vacuum (UHV) conditions. A full atomistic description of the different reaction products based on an unambiguous discrimination between pyrazine and pyridine moieties is presented. Our work not only elucidates that ortho-hydrogen atoms of the pyrazine rings are preferentially activated over their pyridine equivalents, but also sheds new light onto the participation of substrate atoms in metal-organic coordination bonding during covalent C-C bond formation. PMID:27059121

  5. Synthesis and Antifungal Evaluation of 1-Aryl-2-dimethyl-aminomethyl-2-propen-1-one Hydrochlorides

    Mehmet Emin Topaloglu

    2011-06-01

    Full Text Available The development of resistance to current antifungal therapeutics drives the search for new effective agents. The fact that several acetophenone-derived Mannich bases had shown remarkable antifungal activities in our previous studies led us to design and synthesize some acetophenone-derived Mannich bases, 1-8 and 2-acetylthiophene-derived Mannich base 9, 1-aryl-2-dimethylaminomethyl-2-propen-1-one hydrochloride, to evaluate their antifungal activities. The designed chemical structures have ?,?-unsaturated ketone moieties, which are responsible for the bioactivities of the Mannich bases. The aryl part was C6H5 (1; 4-CH3C6H4 (2; 4-CH3OC6H4 (3; 4-ClC6H4 (4; 4-FC6H4 (5; 4-BrC6H4 (6; 4-HOC6H4 (7; 4-NO2C6H4 (8; and C4H3S(2-yl (9. In this study the designed compounds were synthesized by the conventional heating method and also by the microwave irradiation method to compare these methods in terms of reaction times and yields to find an optimum synthetic method, which can be applied for the synthesis of Mannich bases in further studies. Since there are limited number of studies reporting the synthesis of Mannich bases by microwave irradiation, this study may also contribute to the general literature on Mannich bases. Compound 7 was reported for the first time. Antifungal activities of all compounds and synthesis of the compounds by microwave irradiation were also reported for the first time by this study. Fungi (15 species were used for antifungal activity test. Amphotericin B was tested as an antifungal reference compound. In conclusion, compounds 1-6, and 9, which had more potent (216 times antifungal activity than the reference compound amphotericin B against some fungi, can be model compounds for further studies to develop new antifungal agents. In addition, microwave irradiation can be considered to reduce reaction period, while the conventional method can still be considered to obtain compounds with higher reaction yields in the synthesis of new Mannich bases.

  6. FERRIC ION-SPECIFIC SEQUESTERING AGENTS. 7. SYNTHESIS, IRON EXCHANGE KINETICS, AND STABILITY CONSTANTS OF N-SUBSTITUTED, SULFONATED CATECHOYLAMIDE ANALOGUES OF ENTEROBACTIN.

    Pecoraro, Vincent L.; Weitl, Frederick L.; Raymond, Kenneth N.

    1980-10-01

    For treatment of chronic iron overload (as occurs in Cooley's anemia), ferric ion sequestering agents with specific properties are necessary. Two analogues of enterobactin [a microbial chelating agent with the greatest stability constant known for an Fe(III) complex] are reported which exhibit: i) hydrolytic stability; ii) water solubility; iii) N-substitution to block peptidase hydrolysis. The first compound, N,N',N"- trimethyl-N,N',N"-tris(2,3-dihydroxysulfobenzoyl)1,3,5-triaminomethyl- benzene, [Me{sub 3}MECAMS, 6] was prepared from the amide of trimesloyl chloride (1) and MeNH{sub 2}. The resulting amide was reduced to the triamine (3) and converted in three steps to the final product 6 in 6% overall yield. The proton-dependent formation constant (log K*) for the reaction: Fe{sup 3+} + H{sub 3}L{sup 6-} = FeL{sup 6-} + 3H{sup +} is 4.87, which gives an equilibrium concentration of [Fe{sup 3+}] at pH 7.4 of 2 x 10{sup -27} M for 10{sup -5} M L (6) and 10{sup -6} M total Fe{sup 3+}. The estimated formation constant (log {beta}{sub 110}) is 40. At low pH the FeL{sup 6-} complex undergoes a series of three, one-proton reactions which probably gives a tris-salicylate complex formed by the carbonyl and ortho-catechol oxygen of the 2,3~dihydroxybenzoyl units (the same reaction that occurs with ferric enterobactin). After six hours in the presence of 6 mM ascorbate, Me{sub 3}MECAMS (6.0 mM) removed 3.7% of the ferric ion initially sequestered by the iron storage protein, ferritin. The human iron transport protein transferrin goves up iron to Me{sub 3}MECAMS with a pseudo first-order rate constant of 1.9 x 10{sup -3}min{sup -1} (ligand concentration 2 X 10{sup -4} M). This rate is comparable to that of enterobactin and other catechoyl amide sequestering agents. and greatly exceeds that of desferrioxamine B (Desferal{reg-sign}). the current drug of choice in treating iron overload. Two related compounds have been prepared in which the catechol ring is attached to the amide nitrogen through a methylene group, with amide formation with an acetyl group. In N,N',N"-triacetyl-N,N' ,N"-tris(2,3- dihydroxysulfobenzoyl) -N,N',N"-triaminomethylbenzene [NAcMECAMS, 111... and its unsulfonated precursor, the amide linkage of the catechoyl amides such as Me{sub 3}MECAMS (6) has been shifted from an endo position relative to the benzene and catechol rings to an exo position in which the amide carbonyl is not conjugated with the catechol ring and cannot form a stable chelate ring in conjunction with a catechol oxygen. The preparation of 11 and 10 proceeded from the previously described precursor of TRIMCAM, 7. borane reduction to the tri.amine 8, and amide formation with acetyl chloride to 9, followed by deprotection of the catechol oxygens with BBr{sub 3}/CH{sub 2}Cl{sub 2} to give 10. Sulfonation of 10 to NAcMECAMS, 11, is carried out in fuming sulfuric acid. In comparison with Me{sub 3}MECAMS, the protonation of NAcMECAMS (11) proceeds by an initial two-proton step in contrast to the one-proton reactions typical of the catechoyl amides, which can form a salicylate mode of coordination involving the amide carbonyl group. Also as a result of the removal of the carbonyl group from conjugation with the catechol ring, the acidity of NAcMECAMS (11) is less than Me{sub 3}MECAMS (6). While the estimated log {beta{sub 110} is approximately the same as for Me{sub 3}MECAMS (40). the effective formation constant (log K*) and pM.(- log [Fe{sub aq}{sup 3+}] ) values are lower (4.0 and 25.0, respectively).

  7. Ligand-controlled ?- and ?-arylation of acyclic N-Boc amines.

    Millet, Anthony; Dailler, David; Larini, Paolo; Baudoin, Olivier

    2014-03-01

    The palladium-catalyzed ligand-controlled arylation of ?-zincated acyclic amines, obtained by directed ?-lithiation and transmetalation, is described. Whereas PtBu3 gave rise to ?-arylated Boc-protected amines, more flexible N-phenylazole-based phosphine ligands induced major ?-arylation through migrative cross-coupling. PMID:24504659

  8. Photoreactive molecular layers containing aryl ester units: Preparation, UV patterning and post-exposure modification

    Hoefler, Thomas [Institute for Chemistry and Technology of Materials, Graz University of Technology, Stremayrgasse 16, A-8010 Graz (Austria); Track, Anna M. [Institute of Solid State Physics, Graz University of Technology, Petersgasse 16/II, A-8010 Graz (Austria); Institute of Physics, University of Graz, Universitaetsplatz 5, A-8010 Graz (Austria); Pacher, Peter [Institute of Solid State Physics, Graz University of Technology, Petersgasse 16/II, A-8010 Graz (Austria); Shen, Quan [Institute of Physics, Montanuniversitaet Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Flesch, Heinz-Georg [Institute of Solid State Physics, Graz University of Technology, Petersgasse 16/II, A-8010 Graz (Austria); Hlawacek, Gregor [Institute of Physics, Montanuniversitaet Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Koller, Georg; Ramsey, Michael G. [Institute of Physics, University of Graz, Universitaetsplatz 5, A-8010 Graz (Austria); Schennach, Robert; Resel, Roland [Institute of Solid State Physics, Graz University of Technology, Petersgasse 16/II, A-8010 Graz (Austria); Teichert, Christian [Institute of Physics, Montanuniversitaet Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Kern, Wolfgang [Institute of Chemistry of Polymers, Montanuniversitaet Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria); Trimmel, Gregor [Institute for Chemistry and Technology of Materials, Graz University of Technology, Stremayrgasse 16, A-8010 Graz (Austria); Griesser, Thomas, E-mail: thomas.griesser@unileoben.ac.at [Institute for Chemistry and Technology of Materials, Graz University of Technology, Stremayrgasse 16, A-8010 Graz (Austria); Institute of Chemistry of Polymers, Montanuniversitaet Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria)

    2010-01-15

    The photolithographic modification of thin functional silane layers provides a versatile and powerful means of fabricating functionalized patterned surfaces which can be applied for tuning inorganic surface properties and for modern immobilisation techniques. In this contribution we present the synthesis of a new functional trichloro organosilane bearing photoreactive aryl ester groups and its application in thin silane layers on silicon oxide surfaces. Whereas the trichlorosilyl group acts as anchoring unit to the inorganic surface, the aryl ester group undergoes the photo-Fries rearrangement to yield hydroxyketones upon irradiation with UV-light of 254 nm which leads to a change in chemical reactivity of the surface. By a subsequent reaction with perfluorobutyryl chloride, the photogenerated hydroxy groups yield the corresponding perfluorinated ester compound, which allows further tuning of surface properties. The layer formation as well as the photoreaction and post-modification reaction was monitored by FTIR spectroscopy and X-ray photoelectron spectroscopy (XPS). The thickness of the obtained thin layers was determined by X-ray reflectivity (XRR). Photopatterned surfaces were produced using a contact mask during illumination followed by the post-modification reaction. Friction force microscopy (FFM) revealed the contrast between modified and unmodified regions of the patterned samples.

  9. Aryl end-capped quaterthiophenes applied as anode interfacial layers in inverted organic solar cells

    Heiskanen, Juha P., E-mail: juha.heiskanen@oulu.fi [Department of Chemistry, P.O. Box 3000, FI-90014 University of Oulu (Finland); Manninen, Venla M. [Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere (Finland); Pankov, Dmitri [Department of Chemistry, P.O. Box 3000, FI-90014 University of Oulu (Finland); Omar, Walaa A.E. [Department of Chemistry, P.O. Box 3000, FI-90014 University of Oulu (Finland); Department of Chemistry and Mathematics, Faculty of Petroleum and Mining Engineering, Suez University, Suez 43721 (Egypt); Kastinen, Tuuva; Hukka, Terttu I.; Lemmetyinen, Helge J. [Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere (Finland); Hormi, Osmo E.O. [Department of Chemistry, P.O. Box 3000, FI-90014 University of Oulu (Finland)

    2015-01-01

    Four aryl end-capped quaterthiophene derivatives were synthesized and their material properties were studied by computational, spectroscopic, electrochemical, and thermoanalytical methods. Compounds were applied as interfacial layers between the bulk heterojunction active layer and Ag anode in inverted organic solar cells. Results show that p-cyanophenyl end-capped quaterthiophene with hexyl side chains increases both the short circuit current density and power conversion efficiency notably compared to reference interlayer material, tris-(8-hydroxyquinoline)aluminum. The improved cell performance was attributed to the optimal positions of the highest occupied molecular orbital and the lowest unoccupied molecular orbital (LUMO) of this material, relative to those of the photoactive electron donor poly(3-hexylthiophene) and Ag anode, and evenly distributed LUMO. In addition, the use of these materials as an anode interfacial layer increases the absorption of the solar cell, which could contribute to the formation of excitons and additional current production by the cell. - Highlights: • Aryl end-capped oligothiophenes were synthesized in good overall yields. • Materials could be applied as anode interfacial layers in organic solar cells. • Computational, spectroscopic, and electrochemical analyses support conclusions. • Substitution patterns determine HOMO and LUMO levels of interfacial material. • Improved cell performance was attributed mainly to optimal HOMO and LUMO levels.

  10. Aryl end-capped quaterthiophenes applied as anode interfacial layers in inverted organic solar cells

    Four aryl end-capped quaterthiophene derivatives were synthesized and their material properties were studied by computational, spectroscopic, electrochemical, and thermoanalytical methods. Compounds were applied as interfacial layers between the bulk heterojunction active layer and Ag anode in inverted organic solar cells. Results show that p-cyanophenyl end-capped quaterthiophene with hexyl side chains increases both the short circuit current density and power conversion efficiency notably compared to reference interlayer material, tris-(8-hydroxyquinoline)aluminum. The improved cell performance was attributed to the optimal positions of the highest occupied molecular orbital and the lowest unoccupied molecular orbital (LUMO) of this material, relative to those of the photoactive electron donor poly(3-hexylthiophene) and Ag anode, and evenly distributed LUMO. In addition, the use of these materials as an anode interfacial layer increases the absorption of the solar cell, which could contribute to the formation of excitons and additional current production by the cell. - Highlights: • Aryl end-capped oligothiophenes were synthesized in good overall yields. • Materials could be applied as anode interfacial layers in organic solar cells. • Computational, spectroscopic, and electrochemical analyses support conclusions. • Substitution patterns determine HOMO and LUMO levels of interfacial material. • Improved cell performance was attributed mainly to optimal HOMO and LUMO levels

  11. SYNTHESIS AND BIOLOGICAL ACTIVITIES OF CERTAIN MESOIONIC SYDNONE COMPOUNDS CONTAINING CHALCONE MOIETY

    Shreenivas R. Deshpande; Pai, K. Vasantakumar

    2010-01-01

    In order to have antibacterial, analgesic and anti-inflammatory activity in the same molecule, 4-[1-oxo-3- (substituted aryl)-2-propenyl]-3-(4-chlorophenyl) sydnones were synthesized by condensing 4-acetyl-3-(4-chlorophenyl)sydnone with various substituted aryl aldehydes and characterized by spectral studies; 4-acetyl-3-(4-chlorophenyl)sydnone itself, was prepared by acetylation of 3-(4-chlorophenyl) sydnone. The newly synthesized compounds were evaluated for antibacterial and anti-inflammato...

  12. N-Aryl-O-glycosyl Haloacetimidates as Glycosyl Donors

    Huchel, Uschi; Tiwari, Pallavi; Schmidt, Richard

    2010-01-01

    Reaction of 1-O-unprotected tetra-O-acetyl- and tetra-O-benzyl-glucopyranose with N-aryl haloacetimidoyl chlorides in the presence of sodium hydride and 15-crown-5 afforded N-aryl-O-glucopyranosyl haloacetimidates. Mainly the β-anomers were obtained in this anomeric O-acylation-type reaction. The glycosyl donor properties of these haloacetimidates were investigated with 6-O- and 4-O-unprotected glucopyranosides as acceptors. The results were compared with those obtained with the corresponding...

  13. Synthesis, characterisation of few N-substituted 1,8-naphthalimide derivatives and their copper(II) complexes

    Nilotpal Barooah; Chandan Tamuly; Jubaraj B Baruah

    2005-03-01

    A few 1,8-naphthalimide derivatives with phenyl (1), benzyl (2), 3,4-dimethoxyphenyl ethyl (3), 4-pyridyl (4), 2-hydroxy ethyl (5), 4-pyridylmethyl (6) groups attached to the nitrogen atom are synthesized and characterized. Cyclic voltammograms of all these compounds show one-electron reversible redox cycle (-1.24 V to -1.18 V) due to formation of anion radicals. However, in the case of (5), quenching of this redox process occurs when polyhydroxy-aromatic compounds such as 1,3-dihydroxy benzene and 1,3,5-trihydroxybenzene are added. Copper complexes, namely bis-{N-(4-pyridylmethyl)1,8-naphthalimide}copper (II) perchlorate (8), bis-{N-(4-pyridylmethyl)1,8-naphthalimide}copper (II) perchlorate (9) and bis-{N-(4-pyridylmethyl)phthalimide} copper (II) perchlorate (10) are synthesized and characterised. The complexes (8) and (9) show reversible redox couple of the ligand without any significant interaction with the redox active copper (II) centre.

  14. Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

    Rajendra Surasani

    2012-11-01

    Full Text Available Simple and efficient procedures for palladium-catalyzed cross-coupling reactions of N-substituted 4-bromo-7-azaindole (1H-pyrrole[2,3-b]pyridine, with amides, amines, amino acid esters and phenols through C–N and C–O bond formation have been developed. The C–N cross-coupling reaction of amides, amines and amino acid esters takes place rapidly by using the combination of Xantphos, Cs2CO3, dioxane and palladium catalyst precursors Pd(OAc2/Pd2(dba3. The combination of Pd(OAc2, Xantphos, K2CO3 and dioxane was found to be crucial for the C–O cross-coupling reaction. This is the first report on coupling of amides, amino acid esters and phenols with N-protected 4-bromo-7-azaindole derivatives.

  15. The synthesis of bisguanidinoalkanes and guanidinoalkanes, N- or N'-substitutes with pyrimidines, as analogues of chlorhexidine

    A series of N,N''' -alkanediylbis[N'-(5-halopyrimidin-2-yl)guanidine] salts has been synthesized along with N,N'''-(trans-cyclohexane-1,4-diyl)bis[N'-(5-chloropyrimidin-2-yl)guanidine], N,N'''-(cis-cyclohexane-1,4-diyl)bis[N'-(5-chloropyrimidin-2-yl)guanidine] dihydrochloride and N-(cis-4-aminocyclohexan-1-yl)-N'-(5-chloropyrimidin-2-yl)guanidine dihydrochloride. Furthermore, a series of N-(alkan-1-yl)-N'-(5-chloropyrimidin-2yl)guanidine hydrochlorides and N-(6-aminohexan-1-yl)-N'-(5-chloropyrimidin-2-yl)guanidine dihydrochloride were synthesized. This series of compounds was prepared by displacement reactions of 2-methylsulfonylpyrimidines with bisguanidinoalkanes or by condensation of 5-chloro-2-cyanoaminopyrimidine (5-chloropyrimidin-2-ylcyanamide) with alkylamines. 19 refs

  16. The synthesis of bisguanidinoalkanes and guanidinoalkanes, N- or N`-substitutes with pyrimidines, as analogues of chlorhexidine

    Elmes, B.C.; Holan, G.; Wernert, G.T.; Winkler, D.A. [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Melbourne, VIC (Australia). Div. of Materials Science

    1996-12-31

    A series of N,N``` -alkanediylbis[N`-(5-halopyrimidin-2-yl)guanidine] salts has been synthesized along with N,N```-(trans-cyclohexane-1,4-diyl)bis[N`-(5-chloropyrimidin-2-yl)guanidine], N,N```-(cis-cyclohexane-1,4-diyl)bis[N`-(5-chloropyrimidin-2-yl)guanidine] dihydrochloride and N-(cis-4-aminocyclohexan-1-yl)-N`-(5-chloropyrimidin-2-yl)guanidine dihydrochloride. Furthermore, a series of N-(alkan-1-yl)-N`-(5-chloropyrimidin-2yl)guanidine hydrochlorides and N-(6-aminohexan-1-yl)-N`-(5-chloropyrimidin-2-yl)guanidine dihydrochloride were synthesized. This series of compounds was prepared by displacement reactions of 2-methylsulfonylpyrimidines with bisguanidinoalkanes or by condensation of 5-chloro-2-cyanoaminopyrimidine (5-chloropyrimidin-2-ylcyanamide) with alkylamines. 19 refs.

  17. SYNTHESIS OF NOVEL N-SUBSTITUTED 2-(1H-BENZOTRIAZOL-1-YL - ACETOHYDRAZIDE DERIVATIVES AS ANTIMICROBIAL AGENTS

    Jimit S. Patel

    2012-06-01

    Full Text Available As a part of research project on the synthesis of number of substituted benzotriazole derivatives with electron donating as well as electron withdrawing groups was done and evaluated them for antibacterial and antifungal activity. First of all benzotriazole was prepared using o-phenylene diamine and sodium nitrite in acidic conditions. Now benzotriazole was reacted with ethyl chloroacetate to form benzotriazole ethyl acetate which was then reacted with hydrazine hydrate to produce benzotriazole acetohydrazide. Finally it was reacted with different sulfonyl chlorides and benzoyl chlorides to give various derivatives. The purity of all compounds have been checked by the TLC monitoring and the confirmation of the structure is checked by different spectral analysis like UV, IR, Mass and NMR and evaluated as antibacterial agent by using sulfacetamide as standard drug and for antifungal activity by using clotrimazole as standard drug.

  18. CuO-promoted construction of N-2-aryl-substituted-1,2,3-triazoles via azide-chalcone oxidative cycloaddition and post-triazole arylation.

    Zhang, Yuanqing; Li, Xiaolong; Li, Jihui; Chen, Jinying; Meng, Xu; Zhao, Mingming; Chen, Baohua

    2012-01-01

    An efficient one-pot three-component stepwise approach for the synthesis of N-2-aryl-substituted-1,2,3-triazoles has been developed. By using this azide-chalcone oxidative cycloaddition and post-triazole arylation, a series of N-2-aryl-substituted-1,2,3-triazoles are readily prepared under mild conditions in excellent yields and high regioselectivity. Both the catalyst and substrates are readily available. PMID:22133007

  19. New Trends in Aryl Hydrocarbon Receptor Biology

    Mulero-Navarro, Sonia; Fernandez-Salguero, Pedro M.

    2016-01-01

    Traditionally considered as a critical intermediate in the toxic and carcinogenic response to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD), the Aryl hydrocarbon/Dioxin receptor (AhR) has proven to be also an important regulator of cell physiology and organ homeostasis. AhR has become an interesting and actual area of research mainly boosted by a significant number of recent studies analyzing its contribution to the proper functioning of the immune, hepatic, cardiovascular, vascular and reproductive systems. At the cellular level, AhR establishes functional interactions with signaling pathways governing cell proliferation and cell cycle, cell morphology, cell adhesion and cell migration. Two exciting new aspects in AhR biology deal with its implication in the control of cell differentiation and its more than likely involvement in cell pluripotency and stemness. In fact, it is possible that AhR could help modulate the balance between differentiation and pluripotency in normal and transformed tumor cells. At the molecular level, AhR regulates an increasingly large array of physiologically relevant genes either by traditional transcription-dependent mechanisms or by unforeseen processes involving genomic insulators, chromatin dynamics and the transcription of mobile genetic elements. AhR is also closely related to epigenetics, not only from the point of view of target gene expression but also with respect to its own regulation by promoter methylation. It is reasonable to consider that deregulation of these many functions could have a causative role, or at least contribute to, human disease. Consequently, several laboratories have proposed that AhR could be a valuable tool as diagnostic marker and/or therapeutic target in human pathologies. An additional point of interest is the possibility of regulating AhR activity by endogenous non-toxic low weight molecules agonist or antagonist molecules that could be present or included in the diet. In this review, we will address these molecular and functional features of AhR biology within physiological and pathological contexts.

  20. Base-Promoted Domino Reaction of 5-Substituted 2-Nitrosophenols with Bromomethyl Aryl Ketones: A Transition-Metal-Free Approach to 2-Aroylbenzoxazoles.

    Aljaar, Nayyef; Malakar, Chandi C; Conrad, Jrgen; Beifuss, Uwe

    2015-11-01

    The reaction of 5-substituted 2-nitrosophenols with bromomethyl aryl ketones and related compounds employing K2CO3 as a base in refluxing THF and DMF at 80 C, respectively, delivers 2-aroylbenzoxazoles in a single step with yields up to 85%. The new method involves an intermolecular nucleophilic substitution followed by intramolecular 1,2-addition and elimination. It allows an efficient and practical access to 2-aroylbenzoxazoles under transition-metal-free conditions. PMID:26399156

  1. Ultrasound promoted and SiO2/CCl3COOH mediated synthesis of 2-aryl-1-arylmethyl-1-benzimidazole derivatives in aqueous media: An eco-friendly approach

    Brajesh Kumar; Kumari Smita; Brajendra Kumar; Luis Cumbal

    2014-11-01

    Ultrasonic irradiation is an efficient and innocuous technique of reagent activation for synthesizing organic compounds. First one-pot synthesis of 2-aryl-1-arylmethyl-1H- benzimidazole derivatives from o- phenylenediamine and an aromatic aldehyde in the presence of silica gel supported trichloroacetic acid (SiTCA) was carried out with excellent yields at 50°C by sonication. This method provided several advantages such as green solvent, inexpensive catalyst, simple experimental methodology, shorter reaction time and higher yield.

  2. Synthesis and characterization of novel poly(imino ketone)s via palladium-catalyzed aryl amination

    Al-Hussaini, Ayman S.

    2005-01-01

    The challenge of the present work was to synthesize and to characterize new classes of N-containing polymers via palladium-catalyzed aryl amination. This work was inspired by a desire to combine the properties of high-performance polymers such as PEKs with those of N-containing conductive polymers such as polyaniline (PANI), poly(aromatic amides) (PAAs), and the ready synthesis of N-containing simple aromatic compound by the Buchwald-Hartwig reaction. Careful investigation of a model reaction...

  3. Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

    Kinfe, Henok H.; Mebrahtu, Fanuel M; Manana, Mandlenkosi M; Kagiso Madumo; Mokela S. Sokamisa

    2015-01-01

    1-C and 2-C-branched carbohydrates are present as substructures in a number of biologically important compounds. Although the synthesis of such carbohydrate derivatives is extensively studied, the synthesis of 1,2-cis-2-C-branched C-, S-, and N-glycosides is less explored. In this article a synthetic strategy for the synthesis of 1,2-cis-2-C-branched-aryl-C-glucosides is reported via a hydrogenolytic desulfurization of suitably orientated carbohydrate based hemithioacetals. 1,2-cis-2-Hydroxym...

  4. Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines.

    Li, Xiaoming; Hilgers, Mark; Cunningham, Mark; Chen, Zhiyong; Trzoss, Michael; Zhang, Junhu; Kohnen, Lucy; Lam, Thanh; Creighton, Chris; G C, Kedar; Nelson, Kirk; Kwan, Bryan; Stidham, Mark; Brown-Driver, Vickie; Shaw, Karen J; Finn, John

    2011-09-15

    Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim (TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains. PMID:21831637

  5. Synthesis, Characterization and Biological Screening of Various O-phenyl-N-aryl Carbamates

    A series of O-phenyl-N-aryl carbamates (3a-i) were synthesized by the reaction of phenyl chloroformate (1) with different aromatic amines (2a-i). The compounds were characterized by IR and 1H-NMR and screened against acetylcholinesterase, butrylcholinesterase and lipoxygenase enzymes. The results revealed that O-phenyl-N-phenyl carbamate (3a) and O-phenyl-N-(3-hydroxyphenyl) carbamate (3e) were active against acetylcholinesterase while O-phenyl-N-benzyl carbamate (3b), O-phenyl-N-(4-hydroxyphenyl) carbamate (3f) and O-phenyl-N-(3-methoxyphenyl) carbamate (3h) exhibited potential inhibitory activity against 5-lipoxygenase. All these carbamates were also assayed for their antimicrobial and hemolytic activities. O-phenyl-N-(2-hydroxyphenyl) carbamate (3d), O-phenyl-N-(4-hydroxyphenyl) carbamate (3f) and O-phenyl-N-(3-methoxyphenyl) carbamate (3h) showed good antimicrobial and hemolytic activity among all the carbamates. (author)

  6. Influence of conjugation axis on the optical and electronic properties of aryl-substituted benzobisoxazoles.

    Tlach, Brian C; Tomlinson, Aime L; Ryno, Alden G; Knoble, Dawn D; Drochner, Dana L; Krager, Kyle J; Jeffries-EL, Malika

    2013-07-01

    Six different 2,6-diethyl-4,8-diarylbenzo[1,2-d:4,5-d']bis(oxazoles) and four different 2,4,6,8-tetraarylbenzobisoxazoles were synthesized in two steps: a Lewis acid catalyzed orthoester cyclization followed by a Suzuki or Stille cross-coupling with various arenes. The influence of aryl group substitution and/or conjugation axis variation on the optical and electronic properties of these benzobis(oxazole) (BBO) compounds was evaluated. Structural modifications could be used to alter the HOMO, LUMO, and band gap over a range of 1.0, 0.5, and 0.5 eV, respectively. However, depending on the location and identity of the substituent, the HOMO level can be altered without significantly impacting the LUMO level. This is supported by the calculated frontier molecular orbitals. Our results indicate that the FMOs and band gaps of benzobisoxazoles can be readily modified either jointly or individually. PMID:23796165

  7. Absorption and fluorescence properties of aryl substituted porphyrins in different media

    Bozkurt, Serap Seyhan; Merdivan, Melek; Ayata, Sevda

    2010-02-01

    Absorption and fluorescence properties of aryl substituted porphyrins, 5,10,15,20-tetra-4-oxy(aceticacid)phenylporphyrin (TAPP), 5,10,15,20-tetra-(4-phenoxyphenyl) porphyrin (TPPP), 5,10,15,20-tetra-(3-bromo-4-hydroxyphenyl) porphyrin (TBHPP), and 5,10,15,20-tetra-p-chloromethylphenyl porphyrin (CMPP) were investigated. The UV/vis absorption, fluorescence and excited spectra as the fluorescence quantum yields and fluorescence lifetimes for the compounds were measured in organic solvents (chloroform (CHCl 3), tetrahydrofuran (THF)) and immobilized media (PVC film, sol-gel matrix). The fluorescence quantum yields of TAPP and TPPP were higher than the others. The fluorescence lifetimes of all studied porphyrin derivates were found to be fifty percent lower and their fluorescence intensities were increased fifty percent more in both of immobilized mediums, as compared to organic solvents.

  8. An Efficient Three Component One-Pot Synthesis of 5-Amino-7-aryl-7,8-dihydro-[1,2,4] triazolo[4,3-a]-pyrimidine-6-carbonitriles

    Sun Wan-Fu

    2012-02-01

    Full Text Available A series of novel 5-amino-7-aryl-7,8-dihydro-[1,2,4] triazolo[4,3-a]-pyrimidine-6-carbonitriles were synthesized by a one-pot reaction of 3-amino-1,2,4-triazole, malononitrile and aryl aldehydes in the presence of 20 mol% NaOH in ethanol under heating or ultrasonic irradiation. The structures of the target compounds were confirmed by inspection of their 1H- NMR, 13C-NMR, IR and MS spectra. The advantages of this method are short reaction times, good yields, high selectivity and operational simplicity.

  9. Aryl azoles with neuroprotective activity--parallel synthesis and attempts at target identification.

    Cocconcelli, Giuseppe; Diodato, Enrica; Caricasole, Andrea; Gaviraghi, Giovanni; Genesio, Eva; Ghiron, Chiara; Magnoni, Letizia; Pecchioli, Elena; Plazzi, Pier Vincenzo; Terstappen, Georg C

    2008-02-15

    A parallel synthesis of aryl azoles with neuroprotective activity is described. All compounds obtained were evaluated in an in vitro assay using a NMDA toxicity paradigm showing a neuroprotective activity between 15% and 40%. The potential biological target of the active compounds was investigated by extensive literature searches based around similar scaffolds with reported neuroprotective activity. The most interesting molecules active in the NMDA toxicity assay (3a and 2g) showed moderate but significant activity in the inhibition of the Site 2 Sodium Channel binding assay at 10 microM. To confirm our hypothesis compounds 3a, c, f and 2g were tested in the Veratridine assay which is one of the excitotoxicity assays of relevance to NaV channels. The compounds tested showed an activity between 40% and 70%. The identification of neuroprotective small molecules and the identification of NaV channels as the potential site of action were the most important goals of this work. PMID:18024137

  10. Characterization of Natural Aryl Hydrocarbon Receptor Agonists from Cassia Seed and Rosemary

    Yoshiaki Amakura

    2014-04-01

    Full Text Available Many recent studies have suggested that activation of the aryl hydrocarbon receptor (AhR reduces immune responses, thus suppressing allergies and autoimmune diseases. In our continuing study on natural AhR agonists in foods, we examined the influence of 37 health food materials on the AhR using a reporter gene assay, and found that aqueous ethanol extracts of cassia seed and rosemary had particularly high AhR activity. To characterize the AhR-activating substances in these samples, the chemical constituents of the respective extracts were identified. From an active ethyl acetate fraction of the cassia seed extract, eight aromatic compounds were isolated. Among these compounds, aurantio-obtusin, an anthraquinone, elicited marked AhR activation. Chromatographic separation of an active ethyl acetate fraction of the rosemary extract gave nine compounds. Among these compounds, cirsimaritin induced AhR activity at 10–102 μM, and nepitrin and homoplantagenin, which are flavone glucosides, showed marked AhR activation at 10–103 μM.

  11. Synthesis and Toxicity Evaluation of Some N4-Aryl Substituted 5-Trifluoromethoxyisatin-3-thiosemicarbazones

    Muhammad Yaqub

    2011-07-01

    Full Text Available A series of twenty one N4-aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones 3a-3u was synthesized by the reaction of trifluoromethoxyisatin 1 with different arylthiosemicarbazides 2 in aqueous ethanol (50%, containing a few drops of acetic acid. Their structures were established on the basis of analytical (CHN and spectral (IR, 1H-NMR, EIMS data. All the synthesized compounds were evaluated for their toxicity potential by a brine shrimp lethality bioassay. Ten compounds i.e., 3a, 3e, 3i-3l and 3n-3q proved to be active in this assay, displaying promising toxicity (LD50 = 1.11 × 10−5 M − 1.80 × 10−4 M. Amongst these, 3k, 3n and 3o were found to be the most active ones (LD50 = 1.11 × 10−5 M − 1.43 × 10−5 M. Compound 3k showed the highest activity with a LD50 value of 1.11 × 10−5 M and can, therefore, be used as a lead for further studies. Structure-activity relationship (SAR studies revealed that the presence of strong inductively electron-attracting trifluoromethoxy substituent at position-5 of the isatin moiety played an important role in inducing or enhancing toxic potentiality of some of the synthesized compounds.

  12. A FACILE ONE-POT SYNTHESIS OF NOVEL 1,1′-(ALKANEDIYLBIS(5-OXO-3- ALKYL/ARALKYL/ARYL-1,2,3,4,5,6,7,8-OCTAHYDROQUINAZOLINES and THEIR ANTI-BACTERIAL ACTIVITIES A FACILE ONE-POT Synthese von neuartigen 1,1 '- (Alkandiyl BIS (5-oxo-3- ALKYL/ARALKYL/ARYL-1,2,3,4,5,6,7,8-OCTAHYDROQUINAZOLINES and their Anti-bakterielle AKTIVITÄTEN

    Madhusudhan Saha and Jai N. Vishwakarma

    2013-04-01

    Full Text Available A facile one-pot synthesis of novel 1,1′-(alkanediylbis(5-oxo-3-alkyl/aralkyl/aryl- 1,2,3,4,5,6,7,8-octahydroquinazolines 3a-r has been devised by the cyclocondensation of bisenaminones 2a-f with primary amine and formaldehyde. The structures of the products have been established by spectral and analytical data as 1, 1′-(alkanediylbis(5-oxo-3-alkyl/ aralkyl/aryl-1,2,3,4,5,6,7,8-octahydroquinazolines. Some of the compounds have been found to possess promising anti-bacterial properties.

  13. On the mechanism of the palladium-catalyzed ?-arylation of ester enolates.

    Larini, Paolo; Kefalidis, Christos E; Jazzar, Rodolphe; Renaudat, Alice; Clot, Eric; Baudoin, Olivier

    2012-02-13

    The palladium-catalyzed ?-arylation of ester enolates with aryl bromides was studied both experimentally and computationally. First, the effect of the ligand on the selectivity of the ?/?-arylation reactions of ortho- and meta-fluorobromobenzene was described. Selective ?-arylation was observed for the reaction of o-fluorobromobenzene with a range of biarylphosphine ligands, whereas ?-arylation was predominantly observed with m-fluorobromobenzene for all ligands except DavePhos, which gave an approximate 1:1 mixture of ?-/?-arylated products. Next, the effect of the substitution pattern of the aryl bromide reactant was studied with DavePhos as the ligand. We showed that electronic factors played a major role in the ?/?-arylation selectivity, with electron-withdrawing substituents favoring ?-arylation. Kinetic and deuterium-labeling experiments suggested that the rate-limiting step of ?-arylation with DavePhos as the ligand was the palladium-enolate-to-homoenolate isomerization, which occurs by a ??H-elimination, olefin-rotation, and olefin-insertion sequence. A dimeric oxidative-addition complex, which was shown to be catalytically competent, was isolated and structurally characterized. A common mechanism for ?- and ?-arylation was described by DFT calculations. With DavePhos as the ligand, the pathway leading to ?-arylation was kinetically favored over the pathway leading to ?-arylation, with the palladium-enolate-to-homoenolate isomerization being the rate-limiting step of the ?-arylation pathway and the transition state for olefin insertion its highest point. The nature of the rate-limiting step changed with PCy(3) and PtBu(3) ligands, and with the latter, ?-arylation became kinetically favored. The trend in selectivity observed experimentally with differently substituted aryl bromides agreed well with that observed from the calculations. The presence of electron-withdrawing groups on these bromides mainly affected the ?-arylation pathway by disfavoring C-C reductive elimination. The higher activity of the ligands of the biaryldialkylphosphine ligands compared to their corresponding trialkylphosphines could be attributed to stabilizing interactions between the biaryl backbone of the ligands and the metal center, thereby preventing deactivation of the ?-arylation pathway. PMID:22241631

  14. The synthesis, X-ray crystal structure and optical properties of novel 5-aryl-3-ferrocenyl-1-pyridazinyl-pyrazoline derivatives.

    Gong, Zhong-Liang; Xie, Yong-Sheng; Zhao, Bao-Xiang; Lv, Hong-Shui; Liu, Wei-Yong; Zheng, Liang-Wen; Lian, Song

    2011-01-01

    A series of novel 5-aryl-3-ferrocenyl-1-pyridazinyl pyrazoline derivatives was synthesized by the reaction of ferrocenyl chalcone and 3-chloro-6-hydrazinylpyridazine in 10-65% yields. The compounds were characterized using IR, (1)H NMR, HRMS spectroscopic techniques and representative compounds 3c and 4c were assigned based on the X-ray crystallographic structure. The absorption and fluorescence characteristics of the compounds were investigated in chloroform, tetrahydrofuran and acetonitrile, respectively. The results showed that the absorption maxima of the compounds varied from 323 to 327 nm depending on the groups bonded to benzene and pyridazine ring. The maximum emission spectra of compounds in CHCl(3) were dependent on groups in pyridazine ring in which a strong donating-electron group such as propoxyl group on pyridazine ring in N-1 position of pyrazoline made the emission wavelength of 4a-4e small red shifte than that of compounds 3a-3e with chlorine group. The intensity of absorption and fluorescence was also correlated with substituent on aryl ring in C-5 position of pyrazoline. In addition, the absorption spectra of these compounds changed very little, but the fluorescence spectra had much change with increasing solvent polarity. PMID:20890645

  15. A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

    Galvis-Pareja, David [Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Zapata-Torres, Gerald [Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago (Chile); Hidalgo, Jorge [Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago (Chile); Ayala, Pedro [Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); and others

    2014-08-15

    Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca{sup 2+} channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca{sup 2+} channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca{sup 2+} channel-blocking activity and antioxidant properties. The Ca{sup 2+} channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca{sup 2+} channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca{sup 2+} channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca{sup 2+} entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca{sup 2+} blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca{sup 2+} blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties.

  16. The discovery of new potent non-peptide Angiotensin II AT1 receptor blockers: A concise synthesis, molecular docking studies and biological evaluation of N-substituted 5-butylimidazole derivatives

    Agelis, G.; Resvani, A.; Durdagi, S.; Spyridaki, K.; Tůmová, Tereza; Slaninová, Jiřina; Giannopoulos, P.; Vlahakos, D.; Liapakis, G.; Mavromoustakos, T.; Matsoukas, J.

    2012-01-01

    Roč. 55, Sep (2012), s. 358-374. ISSN 0223-5234 Institutional research plan: CEZ:AV0Z40550506 Keywords : synthesis * angiotensin II receptor blockers * N-substituted 5-butylimidazole derivatives * antihypertensive activity * molecular docking Subject RIV: CC - Organic Chemistry Impact factor: 3.499, year: 2012

  17. Radioiodination of Aryl-Alkyl Cyclic Sulfates

    Papisov, Mikhail I.; Chandra Mushti

    2012-01-01

    Among the currently available positron emitters suitable for Positron Emission Tomography (PET), 124I has the longest physical half-life (4.2 days). The long half-life and well-investigated behavior of iodine in vivo makes 124I very attractive for pharmacological studies. In this communication, we describe a simple yet effective method for the synthesis of novel 124I labeled compounds intended for PET imaging of arylsulfatase activity in vivo. Arylsulfatases have important biological function...

  18. Síntese de beta-N-acetilglicosaminídeos de arila modificados em C-6 como potenciais agentes antimicrobianos Synthesis of aryl beta-N-acetylglucosaminedes modified at C-6 as potential antimicrovial agents

    Rozângela Magalhães Manfrini; José Dias de Souza Filho; Rute Cunha Figueiredo; Allison Fabiano D'Angelis; Maria Auxiliadora Fontes Prado; Elzíria de Aguiar Nunan; Gabriela Aires Martins; Ricardo José Alves/

    2008-01-01

    We report herein the synthesis of aryl beta-N-acetylglucosaminides containing azido, amino and acetamido groups at C-6 as potential antimicrobial agents. It was expected that these compounds could interfere with the biosynthesis and/or biotransformation of N-acetylglucosamine in fungi and bacteria. None of the compounds showed antimicrobial activity against bacteria (Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa), filamentous fungus ...

  19. Binding of Estrogenic Compounds to Recombinant Estrogen Receptor-α: Application to Environmental Analysis

    Pillon, Arnaud; Boussioux, Anne-Marie; Escande, Aurélie; Aït-Aïssa, Sélim; Gomez, Elena; Fenet, Hélène; Ruff, Marc; Moras, Dino; Vignon, Françoise; Duchesne, Marie-Josèphe; Casellas, Claude; Nicolas, Jean-Claude; Balaguer, Patrick

    2004-01-01

    Estrogenic activity in environmental samples could be mediated through a wide variety of compounds and by various mechanisms. High-affinity compounds for estrogen receptors (ERs), such as natural or synthetic estrogens, as well as low-affinity compounds such as alkylphenols, phthalates, and polychlorinated biphenyls are present in water and sediment samples. Furthermore, compounds such as polycyclic aromatic hydrocarbons, which do not bind ERs, modulate estrogen activity by means of the aryl ...

  20. Functionalization of poly(aryl ether ether ketone)

    Wang, Fei; Roovers, J. [Institute for Environmental Chemistry, Ontario (Canada)

    1993-12-31

    Bromomethyl and dibromomethyl substituted poly(aryl ether ether ketone) have been prepared from methyl poly(aryl ether ether ketone) by bromination with bromine. These brominated polymers are intermediates that can be further functionalized by: hydrolysis, oxidation, substitution etc. A series of new functionalized PEEK polymers has been prepared. The functional group includes -CH{sub 2}OH, -CH{sub 2}OCH{sub 3}, -CHO, -COOH, -COOCH{sub 3}, -CH{sub 2}CN, -CH{sub 2}COOH, -CH{sub 2}OCOCH{sub 3}, -CH{sub 2}N{sup +}H(CH{sub 2}CH{sub 3}){sub 2}Br{sup {minus}}, -CH{sub 2}N(CH{sub 2}CH{sub 3}){sub 2}, -CH{sub 2}N{sup +}H(CH{sub 2}CH{sub 3}){sub 3}Br{sup {minus}}.

  1. Group 9 Metal Complexes of meso-Aryl-Substituted Rubyrin.

    Soya, Takanori; Osuka, Atsuhiro

    2015-07-20

    Invited for the cover of this issue are Takanori Soya and Atsuhiro Osuka at Kyoto University. The image depicts Group 9 metal (Co, Rh, and Ir) complexes of meso-aryl-substituted rubyrin and a meteorite approaching to the atmosphere. A large amount of Iridium is often contained in meteorites. Read the full text of the article at 10.1002/chem.201501080. PMID:26042817

  2. Aryl Polyphosphonates: Useful Halogen-Free Flame Retardants for Polymers

    Li Chen; Yu-Zhong Wang

    2010-01-01

    Aryl polyphosphonates (ArPPN) have been demonstrated to function in wide applications as flame retardants for different polymer materials, including thermosets, polycarbonate, polyesters and polyamides, particularly due to their satisfactory thermal stability compared to aliphatic flame retardants, and to their desirable flow behavior observed during the processing of polymeric materials. This paper provides a brief overview of the main developments in ArPPN and their derivatives for flame-re...

  3. The aryl hydrocarbon receptor promotes aging phenotypes across species

    Anna Eckers; Sascha Jakob; Christian Heiss; Thomas Haarmann-Stemmann; Christine Goy; Vanessa Brinkmann; Cortese-Krott, Miriam M.; Roberto Sansone; Charlotte Esser; Niloofar Ale-Agha; Joachim Altschmied; Natascia Ventura; Judith Haendeler

    2016-01-01

    The ubiquitously expressed aryl hydrocarbon receptor (AhR) induces drug metabolizing enzymes as well as regulators of cell growth, differentiation and apoptosis. Certain AhR ligands promote atherosclerosis, an age-associated vascular disease. Therefore, we investigated the role of AhR in vascular functionality and aging. We report a lower pulse wave velocity in young and old AhR-deficient mice, indicative of enhanced vessel elasticity. Moreover, endothelial nitric oxide synthase (eNOS) showed...

  4. Asymmetric ?-arylation of ?-amino acids via rearrangement of urea derivatives

    Atkinson, Rachel Clare

    2015-01-01

    Quaternary amino acids are biologically important and useful building blocks for both natural product and pharmaceutical targets. They can be made from their naturally occurring proteinogenic tertiary counterparts through methods such as alkylation. However, ?-arylation of amino acids is challenging with only a small number of methods available, which are far from general and access only a limited substrate scope.The N to C rearrangement chemistry established in the Clayden group allowed us t...

  5. Kumada coupling of aryl, heteroaryl, and vinyl chlorides catalyzed by amido pincer nickel complexes.

    Liu, Ning; Wang, Zhong-Xia

    2011-12-16

    A series of amido pincer complexes of nickel were examined for their catalysis in the Kumada cross-coupling reaction. The P,N,O-pincer nickel complexes tested are active catalysts for the cross-coupling of aryl, heteroaryl, and vinyl chlorides with aryl Grignard reagents. The reactions can proceed at room temperature and tolerate functional groups in aryl chlorides with the aid of LiCl and ZnCl(2) additives. PMID:22077596

  6. Transition metal-catalyzed arylation of unactivated C(sp3)-H bonds.

    Baudoin, Olivier

    2011-10-01

    Transition-metal-catalyzed C-H bond arylation has recently emerged as a powerful tool for the functionalization of organic molecules that may complement or even replace traditional catalytic cross-couplings. While many efforts have focused on the arylation of arenes and heteroarenes in the past two decades, less studies have been devoted to the arylation of nonacidic C-H bonds of alkyl groups. This tutorial review highlights recent work in this active area. PMID:21505712

  7. Carbamoylation of aryl halides by molybdenum or tungsten carbonyl amine complexes.

    Ren, Wei; Yamane, Motoki

    2010-05-01

    When aryl halide is treated with molybdenum carbonyl amine complex in the presence of base, carbamoylation proceeds to give amide in good yield. The proposed mechanism involves oxidative addition of aryl halide to molybdenum(0) complex, migratory insertion to carbon monoxide giving acyl(amino)molybdenum(II) or aryl(carbamoyl)molybdenum(II) intermediate, and reductive elimination of the amide. This method is simple and provides an alternative method to the conventional palladium-catalyzed amide formation using gaseous carbon monoxide. PMID:20349980

  8. 2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.

    Ryu, HyungChul; Seo, Sejin; Kim, Myeong Seop; Kim, Mi-Yeon; Kim, Ho Shin; Ann, Jihyae; Tran, Phuong-Thao; Hoang, Van-Hai; Byun, Jieun; Cui, Minghua; Son, Karam; Sharma, Pankaz Kumar; Choi, Sun; Blumberg, Peter M; Frank-Foltyn, Robert; Bahrenberg, Gregor; Koegel, Babette-Yvonne; Christoph, Thomas; Frormann, Sven; Lee, Jeewoo

    2014-08-15

    A series of 2-aryl pyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Multiple compounds showed highly potent TRPV1 antagonism toward capsaicin comparable to previous lead 7. Among them, compound 9 demonstrated anti-allodynia in a mouse neuropathic pain model and blocked capsaicin-induced hypothermia in a dose-dependent manner. Docking analysis of 9 with our hTRPV1 homology model provided insight into its specific binding mode. PMID:25011915

  9. Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action

    Fangfang Tan; Baojun Shi; Jian Li; Wenjun Wu; Jiwen Zhang

    2015-01-01

    Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that the compounds (S)-2-(2′-hydroxyphenyl)-4-hydroxy-methyl- 4,5-dihydrothiazole (7h) and (R)-2-(2′-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydro-thiazole (7h′) exhibited significant i...

  10. A quantitative structure-activity relationship study of novel inhibitors of cyclooxygenase-2: The 5-aryl-2,2-dialkyl-4-phenyl-3(2 Hfuranone derivatives

    Singh P

    2007-01-01

    Full Text Available The cyclooxygenase-2 enzyme inhibition activity of 5-aryl-2,2-dialkyl-4-phenyl-3(2 H furanone derivatives is quantitatively analyzed through Fujita-Ban and Hansch type of approaches. The analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory activity of these congeners. From both approaches it is revealed that more hydrophobic susbtituents at 4- R1, a non-hydrogen bond acceptor substitutent, preferably a -F substituent, at 3- R1 in 4-phenyl ring of 3(2 H furanone scaffold improve inhibitory action of a compound. The substituents exhibiting collective molecular bulk smaller than spirocyclopentyl at X and Y positions are preferred as these geminal positions seems to be involved in steric interation. Similarly, 4-aminosulfonyl in 5-aryl ring of 3(2 H furanone moiety emerged as a better choice than 4-methylsulfonyl substitution.

  11. Simple and efficient synthesis of [Formula: see text]-aryl-[Formula: see text]-deoxyguanosine analogs by azide-alkyne click reaction and their antileishmanial activities.

    Daligaux, Pierre; Pomel, Sébastien; Leblanc, Karine; Loiseau, Philippe M; Cavé, Christian

    2016-05-01

    A series of non-hydrolysable [Formula: see text]-aryl substituted GDP analogs has been synthesized by reacting [Formula: see text]-azido-[Formula: see text]-deoxyguanosine with different aryl- and benzyloxy-alkynes. Cu(I) nanoparticles in water were found to be the most efficient catalyst, producing the desired [Formula: see text]-arylguanosines with good yields. The synthesized compounds were screened for in vitro antileishmanial activity against Leishmania donovani axenic amastigotes and intramacrophage amastigotes stages. The 4-(3-nitrobenzyl)-1,2,3-triazole [Formula: see text]-substituted guanosine analog was found to be the most active in the series with an IC[Formula: see text] of [Formula: see text] on axenic amastigotes. Despite a rather low in vitro antileishmanial activity on the intramacrophage amastigotes, the absence of cytotoxicity on RAW 264.7 macrophages justifies further pharmacomodulations making this antileishmanial series promising. PMID:26754628

  12. Synthesis of Novel Aryl(heteroarylsulfonyl Ureas of Possible Biological Interest

    Maria Gdaniec

    2010-02-01

    Full Text Available The course of reaction of aryl and heteroaryl sulfonamides with diphenylcarbonate (DPC and 4-dimethylaminopyridine (DMAP was found to depend on the pKa of the sulfonamide used. Aryl sulfonamides with pKa ~ 10 gave 4-dimethylamino-pyridinium arylsulfonyl-carbamoylides, while the more acidic heteroaryl sulfonamides (pKa ~ 8 furnished 4-dimethylaminopyridinium heteroarylsulfonyl carbamates. Both the carbamoylides and carbamate salts reacted with aliphatic and aromatic amines with the formation of appropriate aryl(heteroarylsulfonyl ureas, and therefore, can be regarded as safe and stable substitutes of the hazardous and difficult to handle aryl(heteroarylsulfonyl isocyanates.

  13. Microwave Assisted Solvent Free Synthesis of Azomethines from Aryl Aldehydes on Melamin Formaldehyde as Solid Support

    Ramin Rezaei; Mohammadi, Mohammad K; Tahereh Ranjbar

    2011-01-01

    Various aryl aldehydes underwent prompt one pot conversion into the corresponding azomethines in high yields by reacting with hydroxylamine hydrochloride supported on melamine formaldehyde under microwave irradiation.

  14. Synthesis and characterization of 5-heteroarylsulfanyl-4-aryl-1,2,3-selena/thiadiazoles

    Ramaiyan Manikannan; Masilamani Shanmugaraja; Seetharaman Manojveer; Shanmugam Muthusubramanian

    2012-03-01

    Synthesis and spectral characterization of 2-methyl-5-[(4-aryl-1,2,3-selenadiazol-5-yl)sulfanyl]-1,3,4-thiadiazoles, 5-[4-aryl-1,2,3-selenadiazol-5-yl]sulfanyl-1-phenyl-1-1,2,3,4-tetraazoles, 4-aryl-5-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-1,2,3-thiadiazole and 5-[4-aryl-1,2,3-thiadiazol-5-yl]sulfanyl-1-phenyl-1-1,2,3,4-tetraazole have been reported.

  15. Discovery of 5-aryl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones as positive allosteric modulators of metabotropic glutamate subtype-2 (mGlu2) receptors with efficacy in a preclinical model of psychosis.

    Layton, Mark E; Reif, Alexander J; Hartingh, Timothy J; Rodzinak, Kevin; Dudkin, Vadim; Wang, Cheng; Arrington, Ken; Kelly, Michael J; Garbaccio, Robert M; O'Brien, Julie A; Magliaro, Brian C; Uslaner, Jason M; Huszar, Sarah L; Fillgrove, Kerry L; Tang, Cuyue; Kuo, Yuhsin; Jacobson, Marlene A

    2016-02-15

    Optimization of a benzimidazolone template for potency and physical properties revealed 5-aryl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones as a key template on which to develop a new series of mGlu2 positive allosteric modulators (PAMs). Systematic investigation of aryl-SAR led to the identification of compound 27 as a potent and highly selective mGlu2 PAM with sufficient pharmacokinetics to advance to preclinical models of psychosis. Gratifyingly, compound 27 showed full efficacy in the PCP- and MK-801-induced hyperlocomotion assay in rats at CSF concentrations consistent with mGlu2 PAM potency. PMID:26810316

  16. Theoretical investigations on Rh(III)-catalyzed cross-dehydrogenative aryl-aryl coupling via C-H bond activation.

    Zhao, Dan; Li, Xiaoxi; Han, Keli; Li, Xingwei; Wang, Yong

    2015-03-26

    The reaction mechanism of Rh(III)-catalyzed cross-dehydrogenative aryl-aryl coupling between benzamides and haloarenes was investigated through detailed density functional theoretical (DFT) studies in terms of regioselectivity and deuterium kinetic isotope effects (KIEs). Three possible routes including one PivO(-)-assisted reaction route and two non-PivO(-)-assisted reaction routes have been studied. The calculated results refute the proposed mechanism (without PivO(-)-assisted process) in the experimental paper and demonstrate that the PivO(-)-assisted reaction mechanism is the most favored. Meanwhile, the calculation revealed that the PivO(-) anion plays a crucial role as a proton acceptor in the C-H bond activation, especially when the second C-H activation of haloarenearene proceeds via a S(E)3 mechanism. The S(E)3 mechanism is presented for the Rh(III)-catalyzed aryl-aryl reaction for the first time. Our mechanism is evaluated by the calculations of the para-/meta-regioselectivity and KIEs. And it is found that the second activation process is the rate-determining step of the whole catalytic cycle. All these calculated properties agree well with the experiment and Glorius's proposal that the Rh(III)-catalyzed cross-dehydrogenative C-C coupling reaction proceeds by dual C-H activations. Our theoretical studies suggest that the Rh(III) complex catalyst strongly affects the mechanisms of the second C-H activation step and thus this work might provide insight into the design of new catalytic systems. PMID:25693049

  17. Potential of aryl-urea-benzofuranylthiazoles hybrids as multitasking agents in Alzheimer's disease.

    Kurt, Belma Zengin; Gazioglu, Isil; Basile, Livia; Sonmez, Fatih; Ginex, Tiziana; Kucukislamoglu, Mustafa; Guccione, Salvatore

    2015-09-18

    New benzofuranylthiazole derivatives containing the aryl-urea moiety were synthesized and evaluated in vitro as dual acetylcholinesterase (AChE)-butyrylcholinesterase (BuChE) inhibitors. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were assayed. The result showed that all the synthesized compounds exhibited inhibitory activity on both AChE and BuChE with 1-(4-(5-bromobenzofuran-2-yl)thiazol-2-yl)-3-(2-fluorophenyl)urea (e25, IC50 value of 3.85 μM) and 1-(4-iodophenyl)-3-(4-(5-nitrobenzofuran-2-yl)thiazol-2-yl)urea (e38, IC50 value of 2.03 μM) as the strongest inhibitors against AChE and BuChE, respectively. Compound e38 was 8.5-fold more potent than galanthamine. The selectivity index of e25 and e38 was 2.40 and 0.37 against AChE and BuChE, respectively. Compound e2, e4 and e11 (IC50 = 0.2, 0.5 and 1.13 μM, respectively) showed a better ABTS cation radical scavenging ability than the standard quercetin (IC50 = 1.18 μM). Best poses of compounds e38 on BuChE and e25 on AChE indicate that the thiazole ring and the amidic moiety are important sites of interaction with both ChEs. In addition, the benzofuran ring and phenyl ring are anchored to the side chains of both enzymes by π-π(pi-pi) interactions. PMID:26244990

  18. Synthesis and biological activities of certain mesoionic sydnone compounds containing chalcone moiety.

    Deshpande, Shreenivas R; Pai, K Vasantakumar

    2010-06-01

    In order to have antibacterial, analgesic and anti-inflammatory activity in the same molecule, 4-[1-oxo-3- (substituted aryl)-2-propenyl]-3-(4-chlorophenyl) sydnones were synthesized by condensing 4-acetyl-3-(4-chlorophenyl)sydnone with various substituted aryl aldehydes and characterized by spectral studies; 4-acetyl-3-(4-chlorophenyl)sydnone itself, was prepared by acetylation of 3-(4-chlorophenyl) sydnone. The newly synthesized compounds were evaluated for antibacterial and anti-inflammatory activities by cup plate and carrageenan induced rat paw edema methods respectively. Some of the compounds showed promising antibacterial and anti-inflammatory activities. PMID:24825982

  19. Synthesis and antibacterial activity of 2-(2,4-dinitrophenyl-3,5-diphenyl (substituted-6-aryl-3,3a,5,6-tetrahydro-2H-pyrazolo[3,4-d] thiazoles

    Sahu S

    2006-01-01

    Full Text Available Condensation of substituted benzaldehydes with primary aryl amines gave a series of Schiff bases(1a 1 -e 1 ,a 2 ,b 2 ,d 2 ,b 3 -e 3 which, on reaction with thioglycolic acid, resulted in the formation of the corresponding 4-thiazolidinones(2a 1 -e 1 ,a 2 ,b 2 ,d 2 ,b 3 -e 3 . These compounds, on condensation with substituted benzaldehydes in anhydrous sodium acetate, furnished 2-phenyl(substituted-3-aryl-5-benzilidine(substituted-thiazolidine-4-ones(3a 1 -e 1 ,a 2 ,b 2 ,d 2 , b 3 -e 3 . The latter, on heating with 2,4-dinitrophenyl hydrazine in anhydrous sodium acetate, gave the title compounds(4a 1 -e 1 ,a 2 ,b 2 ,d 2 ,b 3 -e 3 . The structures have been established on the basis of elemental analysis and spectral data. The title compounds have been screened in vitro for their possible antibacterial activity

  20. High-resolution laser spectroscopy and magnetic effect of the B 2 E ' ? X 2 A 2 ' transition of the 15N substituted nitrate radical

    Tada, Kohei; Teramoto, Kanon; Ishiwata, Takashi; Hirota, Eizi; Kasahara, Shunji

    2015-03-01

    Rotationally resolved high-resolution fluorescence excitation spectra of the 0-0 band of the B 2 E ' ? X 2 A 2 ' transition of the 15N substituted nitrate radical were observed for the first time, by crossing a jet-cooled molecular beam and a single-mode dye laser beam at right angles. Several thousand rotational lines were detected in the 15 080-15 103 cm-1 region. We observed the Zeeman splitting of intense lines up to 360 G in order to obtain secure rotational assignment. Two, nine, and seven rotational line pairs with 0.0248 cm-1 spacing were assigned to the transitions from the X 2 A 2 ' (?? = 0, k? = 0, N? = 1, J? = 0.5 and 1.5) to the 2 E3 / 2 ' (J' = 1.5), 2 E1 / 2 ' (J' = 0.5), and 2 E1 / 2 ' (J' = 1.5) levels, respectively, based on the ground state combination differences and the Zeeman splitting patterns. The observed spectrum was complicated due to the vibronic coupling between the bright B 2 E ' (? = 0) state and surrounding dark vibronic states. Some series of rotational lines other than those from the X 2 A 2 ' (J = 0.5 and 1.5) levels were also assigned by the ground state combination differences and the observed Zeeman splitting. The rotational branch structures were identified, and the molecular constants of the B 2 E1 / 2 ' (? = 0) state were estimated by a deperturbed analysis to be T0 = 15 098.20(4) cm-1, B = 0.4282(7) cm-1, and DJ = 4 10-4 cm-1. In the observed region, both the 2 E1 / 2 ' and 2 E3 / 2 ' spin-orbit components were identified, and the spin-orbit interaction constant of the B 2 E ' (? = 0) state was estimated to be -12 cm-1 as the lower limit.

  1. Solvation of dichlorocarbene: complexation with aryl ethers.

    Moss, Robert A; Wang, Lei; Odorisio, Christina M; Zhang, Min; Krogh-Jespersen, Karsten

    2010-01-14

    Dichlorocarbene (CCl(2)), generated by laser flash photolysis of dichlorodiazirine, formed pi- and O-ylidic complexes with aromatic ethers such as anisole, 1,3-dimethoxybenzene, 1,3,5-trimethoxybenzene, dibenzofuran, and dibenzo-18-crown-6 and with the aromatic ester phenyl acetate. These complexes were visualized by UV-vis spectroscopy, and they retarded the addition of CCl(2) to tetramethylethylene by factors of 18-152. Computational studies based on density functional theory provided structures and energetics for the transient species and rationalized their absorption spectra. Complexes were not observed between CCl(2) and simple, nonaromatic ethers such as THF, dioxane, or 18-crown-6, nor did these ethers much affect the addition rate of CCl(2) to tetramethylethylene. Computations also suggested that pi-complexes of CCl(2) and, e.g., mesitylene and durene, were energetically reasonable transients. Although these species were not detected spectroscopically, the aromatic compounds did slow the addition of CCl(2) to tetramethylethylene by factors of 15 and 31, respectively. PMID:19877654

  2. Microwave Assisted Condensation Reactions of 2-Aryl Hydrazonopropanals with Nucleophilic Reagents and Dimethyl Acetylenedicarboxylate

    Rita M. Borik

    2007-08-01

    Full Text Available The reaction of methyl ketones 1a-g with dimethylformamide dimethylacetal (DMFDMA afforded the enaminones 2a-g, which were coupled with diazotized aromatic amines 3a,b to give the corresponding aryl hydrazones 6a-h. Condensation of compounds 6a-h with some aromatic heterocyclic amines afforded iminoarylhydrazones 9a-m. Enaminoazo compounds 12a,b could be obtained from condensation of 6c with secondary amines. The reaction of 6e,h with benzotriazolylacetone yielded 14a,b. Also, the reaction of 6a,b,d-f,h with glycine and hippuric acid in acetic anhydride afforded pyridazinone derivatives 17a-f. Synthesis of pyridazine carboxylic acid derivatives 22a,b from the reaction of 6b,e with dimethyl acetylenedicarboxylate (DMAD in the presence of triphenylphosphine at room temperature is also reported. Most of these reactions were conducted under irradiation in a microwave oven in the absence of solvent in an attempt to improve the product yields and to reduce the reaction times.

  3. New Synthesis and Antiparasitic Activity of Model 5-Aryl-1-methyl-4-nitroimidazoles

    Mustafa M. El-Abadelah

    2009-07-01

    Full Text Available A number of 5-aryl-1-methyl-4-nitroimidazoles 5a-f have been synthesized in good yields by the Suzuki coupling reaction between 5-chloro-1-methyl-4-nitroimidazole (3 and arylboronic acids 4a-f, aided by dichlorobis-(triphenylphosphinepalladium(II, K2CO3, and tetrabutylammonium bromide in water at 70-80 °C. Compounds 5a-f were characterized by elemental analysis, NMR and MS spectral data. On the basis of in vitro screening data, 5-(3-chlorophenyl-1-methyl-4-nitro-1H-imidazole (5fexhibited potent lethal activity against Entamoeba histolytica and Giardia intestinalis with IC50 = 1.47 µM/mL, a value lower by a factor of two than that of the standard drug, metronidazole. The boosted activity of 5f was not accompanied by any increased cytotoxicity.The rest of the series also exhibited potent antiparasitic activity with IC50 valuesin the 1.72-4.43 µM/mL range. The cytotoxicity of the derivatives 5c and 5e was increased compared to the precursor compound, metronidazole, although they remain non-cytotoxic at concentrations much higher than the antiparasitic concentration of the two derivatives.

  4. Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents.

    Kamal, Ahmed; Reddy, T Srinivasa; Vishnuvardhan, M V P S; Nimbarte, Vijaykumar D; Subba Rao, A V; Srinivasulu, Vunnam; Shankaraiah, Nagula

    2015-08-01

    A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.1, 1, 10 and 100 ?M) which showed GI50 values in the range of 0.79-28.2 ?M. Flow cytometric data of these compounds showed increased cells in G2/M phase, which is suggestive of G2/M cell cycle arrest. Further, compounds 5l and 5x showed inhibition of tubulin polymerization and disruption of the formation of microtubules. These compounds induce apoptosis by DNA fragmentation and chromatin condensation as well as by mitochondrial membrane depolarization. In addition, structure activity relationship studies within the series are also discussed. Molecular docking studies of compounds 5l and 5x into the colchicine-binding site of the tubulin, revealed the possible mode of interaction by these compounds. PMID:26169762

  5. MORPHOLOGICAL ALTERATIONS OF STAPHYLOCOCCUS AUREUS CAUSED BY ARYL ALIPHATIC AMINOALCOHOL DERIVATIVE

    Dronova M.

    2015-05-01

    Full Text Available Increasing of antimicrobial resistance has created a critical need of the novel antimicrobial agents. One of the promising chemical classes for its development are aryl aliphatic aminoalcohols. New compounds of this class were synthesized at the Institute of organic chemistry (Kiev, Ukraine, by Y. Korotkiy. After the screening studies compound KVM-194 was selected as the potent antistaphylococcal agent. The aim of the study was to examine ultrastructural changes in the bacterial cells under the influence of the compound KVM-194. Materials and methods. Staphylococcus aureus ATCC 25923 was used in all experiments. The minimum inhibitory concentration was determined by serial macrodilution method in Mueller-Hinton broth. Bacteria were exposed to the 0,5 MIC and 5 MICs of the KVM- 194 for 1 h and 24 h. Ultrastructure of intact and treated Staphylococcus aureus cells was examined by transmission electron microscopy after contrasting by osmium tetraoxide and lead citrate. Results and Discussion. The compound KVM-194 possesses a distinct antibacterial activity against Staphylococcus aureus, the minimum inhibitory concentration is 1.25 ?g/ml. We found that exposure to KVM-194 at a subinhibitory concentration resulted in alterations of the cell morphology even after 1 h of treatment. The roughness of the cell surface and emerging of the intracellular particles of different electron density were observed. Increase of the incubation time to 24 h led to detachment of membrane from cytoplasm, multimembrane structures within cells emergence and formation of nonpolar septum. 1 h exposition to suprainhibitory concentration of KVM-194 resulted in nucleoid fragmentation, septum abnormalities and necrosis of some cells. We found that increasing of the incubation period to 24 h led to exacerbation of alterations: cell wall rupture, leakage of cytoplasm and a large number of lysed cells were registered. Conclusion. Observed alterations, suggest the possible mechanism of action of KVM-194, due to its influence on the cell membrane and intracellular processes.

  6. Rational Ligand Design for the Arylation of Hindered Primary Amines Guided by Reaction Progress Kinetic Analysis

    Ruiz-Castillo, Paula; Blackmond, Donna G.; Buchwald, Stephen L.

    2015-01-01

    We report the Pd-catalyzed arylation of very hindered α,α,α-trisubstituted primary amines. Kinetics-based mechanistic analysis and rational design have led to the development of two biaryl phosphine ligands that allow the transformation to proceed with excellent efficiency. The process was effective in coupling a wide range of functionalized aryl and heteroaryl halides under mild conditions.

  7. Copper-catalyzed arylation of biguanide derivatives via C-N cross-coupling reactions.

    Zhang, Chen; Huang, Bo; Bao, Ai-Qing; Li, Xiao; Guo, Shunna; Zhang, Jin-Quan; Xu, Jun-Zhi; Zhang, Rihao; Cui, Dong-Mei

    2015-12-21

    An efficient copper-catalyzed cross-coupling reaction of biguanide hydrochloride derivatives with both aryl iodides and bromides under mild conditions has been developed. The reaction occurred in good yields and tolerated aryl halides containing functionalities such as nitriles, sulfonamides, ethers, and halogens. Alkyl and cyclic substituted biguanidines were also well tolerated. PMID:26444146

  8. Chemo-, regio-, and stereoselective Heck-Matsuda arylation of allylic alcohols under mild conditions.

    Chaudhari, Tohasib Yusub; Hossian, Asik; Manna, Manash Kumar; Jana, Ranjan

    2015-05-01

    Heck arylation with allylic alcohol is extremely challenging due to chemo-, regio-, and stereoselective scrambling. Here we report a mild protocol for the alcohol selective β- and α-arylation of allylic and cinnamyl alcohols respectively with aryldiazonium salts. The steric and electronic parameters of the alkene play a prominent role in the regioselectivity. PMID:25814005

  9. Oxidative addition of aryl chlorides to monoligated palladium(0): A DFT-SCRF study

    Ahlquist, Mårten Sten Gösta; Norrby, Per-Ola

    2007-01-01

    Oxidative addition of aryl chlorides to palladium has been investigated by hybrid density functional theory methods (B3LYP), including a continuum model describing the solvent implicitly. A series of para-substituted aryl chlorides were studied to see the influence of electronic effects on the re...

  10. Aryl ethynyl anthraquinones: a useful platform for targeting telomeric G-quadruplex structures.

    Percivalle, Claudia; Sissi, Claudia; Greco, Maria Laura; Musetti, Caterina; Mariani, Angelica; Artese, Anna; Costa, Giosu; Perrore, Maria Lucia; Alcaro, Stefano; Freccero, Mauro

    2014-06-14

    Aryl ethynyl anthraquinones have been synthesized by Sonogashira cross-coupling and evaluated as telomeric G-quadruplex ligands, by the FRET melting assay, circular dichroism, the DNA synthesis arrest assay and molecular docking. Both the binding properties and G-quadruplex vs. duplex selectivity are controlled by the structures of the aryl ethynyl moieties. PMID:24789544

  11. A convenient method for the synthesis of radioactively labelled aryl glycosides

    Fluoride-directed methylation of the aryl hydroxyl of hydroxyphenyl glycosides with radioactive methyl iodide allows the incorporation of labels under mild conditions that preserve the glycosidic link. The effectiveness of this approach has been demonstrated by the synthesis of two 14C-labelled aryl ?-glycosides. (Author)

  12. Unusual selectivity-determining factors in the phosphine-free Heck arylation of allyl ethers

    Ambrogio, I.; Fabrizi, G.; Cacchi, S.; Henriksen, Signe Teuber; Fristrup, Peter; Tanner, David Ackland; Norrby, Per-Ola

    2008-01-01

    The Heck reaction of aryl iodides and bromides with allyl ethers has been investigated. Using phosphinefree Pd(OAc)(2) in DNIF at 90 degrees C in the presence of Bu4NOAc, the reaction gave cinnamyl derivatives, usually in good to high yields, with a wide range of aryl halides. The reaction tolera...

  13. Phenanthridine synthesis through iron-catalyzed intramolecular N-arylation of O-acetyl oxime.

    Deb, Indubhusan; Yoshikai, Naohiko

    2013-08-16

    O-Acetyl oximes derived from 2'-arylacetophenones undergo N-O bond cleavage/intramolecular N-arylation in the presence of a catalytic amount of iron(III) acetylacetonate in acetic acid. In combination with the conventional cross-coupling or directed C-H arylation, the reaction offers a convenient route to substituted phenanthridines. PMID:23927785

  14. Palladium-catalyzed carbonylative Heck reaction of aryl bromides with vinyl ethers to 3-alkoxy alkenones and pyrazoles.

    Schranck, Johannes; Wu, Xiao-Feng; Neumann, Helfried; Beller, Matthias

    2012-04-16

    Three COming together: The first carbonylative Heck coupling reaction of aryl bromides and vinyl ethers leading to 1-aryl-3-alkoxy-2-propen-1-ones has been established (see scheme). Based on this coupling methodology, a novel one-pot synthesis of aryl-substituted pyrazoles was also realized. PMID:22422673

  15. In vitro anti-Giardia lamblia activity of 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines, individually and in combination with albendazole.

    Velázquez-Olvera, Stephanía; Salgado-Zamora, Héctor; Jiménez-Cardoso, Enedina; Campos-Aldrete, Maria-Elena; Pérez-González, Cuauhtémoc; Ben Hadda, Taibi

    2016-03-01

    Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole. PMID:26657313

  16. Triazole-assisted ruthenium-catalyzed C-H arylation of aromatic amides.

    Al Mamari, Hamad H; Diers, Emelyne; Ackermann, Lutz

    2014-07-28

    Site-selective ruthenium(II)-catalyzed direct arylation of amides was achieved through C?H cleavages with modular auxiliaries, derived from easily accessible 1,2,3-triazoles. The triazolyldimethylmethyl (TAM) bidentate directing group was prepared in a highly modular fashion through copper(I)-catalyzed 1,3-dipolar cycloaddition and allowed for ruthenium-catalyzed C?H arylations on arenes and heteroarenes, as well as alkenes, by using easy-to-handle aryl bromides as the arylating reagents. The triazole-assisted C?H activation strategy was found to be widely applicable, to occur under mild reaction conditions, and the catalytic system was tolerant of important electrophilic functionalities. Notably, the flexible triazole-based auxiliary proved to be a more potent directing group for the optimized ruthenium(II)-catalyzed direct arylations, compared with pyridyl-substituted amides or substrates derived from 8-aminoquinoline. PMID:24957002

  17. Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride

    Subrata Kumar Chaudhuri; Manabendra Saha; Amit Saha; Sanjay Bhar

    2010-01-01

    4-Aryl-4-oxoesters undergo facile reduction of both the keto and the ester groups with methanolic NaBH4 at room temperature to yield the corresponding 1-aryl-1,4-butanediols whereas 4-alkyl-4-oxoesters furnish the corresponding 1,4-butanolides via selective reduction of the keto moiety. Results of a detailed and systematic investigation of the reaction are described.

  18. Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride.

    Chaudhuri, Subrata Kumar; Saha, Manabendra; Saha, Amit; Bhar, Sanjay

    2010-01-01

    4-Aryl-4-oxoesters undergo facile reduction of both the keto and the ester groups with methanolic NaBH₄ at room temperature to yield the corresponding 1-aryl-1,4-butanediols whereas 4-alkyl-4-oxoesters furnish the corresponding 1,4-butanolides via selective reduction of the keto moiety. Results of a detailed and systematic investigation of the reaction are described. PMID:20978613

  19. Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride

    Subrata Kumar Chaudhuri

    2010-09-01

    Full Text Available 4-Aryl-4-oxoesters undergo facile reduction of both the keto and the ester groups with methanolic NaBH4 at room temperature to yield the corresponding 1-aryl-1,4-butanediols whereas 4-alkyl-4-oxoesters furnish the corresponding 1,4-butanolides via selective reduction of the keto moiety. Results of a detailed and systematic investigation of the reaction are described.

  20. Highly dispersed pd catalyst locked in knitting aryl network polymers for Suzuki-Miyaura coupling reactions of aryl chlorides in aqueous media.

    Li, Buyi; Guan, Zhenhong; Wang, Wei; Yang, Xinjia; Hu, Jianglin; Tan, Bien; Li, Tao

    2012-07-01

    Highly dispersed palladium chloride catalysts locked in triphenylphosphine-functionalized knitting aryl network polymers (KAPs) are developed and exhibit excellent activity under mild conditions in the Suzuki-Miyaura cross-coupling reactions of aryl chlorides in aqueous media. This work highlights that the microporous polymers not only play the role of support materials, but also protect the Pd species from aggregation and precipitation, hence, positively effect the catalysis activity. PMID:22674537

  1. Versatile Route to Arylated Fluoroalkyl Bromide Building Blocks.

    Kaplan, Peter T; Vicic, David A

    2016-02-19

    New difunctionalized and fluoroalkylated silyl reagents have been prepared that react with silver and copper salts to afford active catalysts that can be used to synthesize arylated fluoroalkyl bromide building blocks. It has been shown that the [(phen)Ag(CF2)nBr] intermediates are capable of transferring both the phenanthroline ligand and the fluoroalkyl bromide chain to copper iodide, eliminating the need for a preligated copper salt precursor. The methodology is compatible with various chain lengths of the fluoroalkyl halide functionality. PMID:26820388

  2. Catalytic arylation methods from the academic lab to industrial processes

    Burke, Anthony J

    2014-01-01

    A current view of the challenging field of catalytic arylation reactions. Clearly structured, the chapters in this one-stop resource are arranged according to the reaction type, and focus on novel, efficient and sustainable processes, rather than the well-known and established cross-coupling methods.The entire contents are written by two authors with academic and industrial expertise to ensure consistent coverage of the latest developments in the field, as well as industrial applications, such as C-H activation, iron and gold-catalyzed coupling reactions, cycloadditions or novel methodologies

  3. Role of the Aryl Hydrocarbon Receptor in Colon Neoplasia.

    Xie, Guofeng; Raufman, Jean-Pierre

    2015-01-01

    For both men and women, colorectal cancer (CRC) is the second leading cause of cancer death in the United States, primarily as a consequence of limited therapies for metastatic disease. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor with diverse functions in detoxification of xenobiotics, inflammatory responses, and tissue homeostasis. Emerging evidence indicates that AhR also plays an important role in regulating intestinal cell proliferation and tumorigenesis. Here, we review both the pro- and anti-carcinogenic properties of AhR signaling and its potential role as a therapeutic target in CRC. PMID:26264025

  4. Role of the Aryl Hydrocarbon Receptor in Colon Neoplasia

    Guofeng Xie

    2015-07-01

    Full Text Available For both men and women, colorectal cancer (CRC is the second leading cause of cancer death in the United States, primarily as a consequence of limited therapies for metastatic disease. The aryl hydrocarbon receptor (AhR is a ligand-dependent transcription factor with diverse functions in detoxification of xenobiotics, inflammatory responses, and tissue homeostasis. Emerging evidence indicates that AhR also plays an important role in regulating intestinal cell proliferation and tumorigenesis. Here, we review both the pro- and anti-carcinogenic properties of AhR signaling and its potential role as a therapeutic target in CRC.

  5. Role of the Aryl Hydrocarbon Receptor in Colon Neoplasia

    Xie, Guofeng, E-mail: gxie@medicine.umaryland.edu; Raufman, Jean-Pierre [Division of Gastroenterology and Hepatology, Veterans Administration Maryland Health Care System, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2015-07-31

    For both men and women, colorectal cancer (CRC) is the second leading cause of cancer death in the United States, primarily as a consequence of limited therapies for metastatic disease. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor with diverse functions in detoxification of xenobiotics, inflammatory responses, and tissue homeostasis. Emerging evidence indicates that AhR also plays an important role in regulating intestinal cell proliferation and tumorigenesis. Here, we review both the pro- and anti-carcinogenic properties of AhR signaling and its potential role as a therapeutic target in CRC.

  6. Functionalization of Rhenium Aryl Bonds by O-Atom Transfer

    Bischof, Steven M. [Scripps Research Inst., Jupiter, FL (United States); Cheng, Mu-Jeng [California Inst. of Technology (CalTech), Pasadena, CA (United States); Nielsen, Robert J. [California Inst. of Technology (CalTech), Pasadena, CA (United States); Gunnoe, T. Brent [Univ. of Virginia, Charlottesville, VA (United States); Goddard, William A. [California Inst. of Technology (CalTech), Pasadena, CA (United States); Periana, Roy A. [Scripps Research Inst., Jupiter, FL (United States)

    2011-03-29

    Aryltrioxorhenium (ArReO3) has been demonstrated to show rapid oxy-functionalization upon reaction with O-atom donors, YO, to selectively generate the corresponding phenols in near quantitative yields. 18O-Labeling experiments show that the oxygen in the products is exclusively from YO. DFT studies reveal a 10.7 kcal/mol barrier (Ar = Ph) for oxy-functionalization with H2O2 via a Baeyer-Villiger type mechanism involving nucleophilic attack of the aryl group on an electrophilic oxygen of YO coordinated to rhenium.

  7. Role of the Aryl Hydrocarbon Receptor in Colon Neoplasia

    For both men and women, colorectal cancer (CRC) is the second leading cause of cancer death in the United States, primarily as a consequence of limited therapies for metastatic disease. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor with diverse functions in detoxification of xenobiotics, inflammatory responses, and tissue homeostasis. Emerging evidence indicates that AhR also plays an important role in regulating intestinal cell proliferation and tumorigenesis. Here, we review both the pro- and anti-carcinogenic properties of AhR signaling and its potential role as a therapeutic target in CRC

  8. Design, Synthesis and invivo Evaluation of Novel C-Aryl Glucosides as Potent Sodium-Dependent Glucose Cotransporters Inhibitors for the Treatment of Diabetes.

    Li, Zheng; Wang, Xuekun; Xu, Xue; Qiu, Qianqian; Jiao, Lei; Huang, Wenlong; Qian, Hai

    2015-10-01

    A series of novel C-aryl glucosides with substituents at the 3'-position or cyclization at 3', 4'-positions of the distal aryl ring were designed and synthesized, which might decrease the oxidative metabolism of dapagliflozin. Preliminary evaluation for hypoglycemic effect and the risk of hypoglycemia were carried out both in normal and in streptozotocin-induced diabetic mice. Among the synthesized compounds, compound 19a exerted potency-similarity with dapagliflozin and triggered the hypoglycemic effect in a dose-dependent manner. Besides, compound 19a, even at the high dose of 10mg/kg, revealed a low risk of hypoglycemia. In further studies, 19a exhibited sustained antihyperglycemic effect without particular side-effects in 30-day chronic diabetic mice studies. Moreover, histological changes in the pancreas of diabetic mice indicated 19a might protect pancreatic ?-cell from apoptosis by reducing the damage of glucotoxicity. All of these results demonstrated that compound 19a, with excellent invivo pharmacological activity and safety profile, was considered to be a promising drug candidate for the treatment of diabetes mellitus. PMID:25732240

  9. Synthesis of fluorinated carbazoles via C-H arylation catalyzed by Pd/Cu bimetal system and their antibacterial activities.

    Kong, Xianqiang; Zhang, Huizi; Cao, Changsheng; Zhou, Shengliang; Pang, Guangsheng; Shi, Yanhui

    2016-03-15

    An effective intramolecular C-H arylation reaction catalyzed by a bimetallic catalytic system Pd(OAc)2/CuI for the synthesis of fluorine-substituted carbazoles from corresponding N-phenyl-2-haloaniline derivatives under ligand free conditions is demonstrated. The established method is effective for both N-phenyl-2-bromoaniline and N-phenyl-2-chloroaniline, and requires the low loading of Pd(OAc)2 (0.5mol%). A series of new fluorinated carbazoles were synthesized in excellent yields using the protocol (>83%, 19 examples) and were fully characterized by (1)H, (13)C and (19)F NMR spectral data, HRMS and elemental analysis. All compounds were evaluated for their antibacterial activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and methicillin-resistant S. aureus with resistance to gentamicin) by serial dilution technique. All tested compounds showed antibacterial activity against three test strains (S. aureus, B. subtilis and MRSA), and most of these compounds displayed pronounced antimicrobial activities against these three strains with low MIC values ranging from 0.39 to 6.25μg/mL. Among them, compounds 7 and 14 exhibited potent inhibitory activity better than reference drugs meropenem and streptomycin. Three compounds (2, 4 and 5) showed antibacterial activity against E. coli. with MIC values from 12.5 to 25μg/mL. PMID:26879853

  10. Ethyl 3-(2,4-dioxocyclohexyl)propanoate as a novel precursor for N-substituted 4,4a,5,6-tetrahydroquinoline-2,7(1H,3H)-diones and their corresponding 3,4-dihydro-7-hydroxyquinolin-2(1H)-ones and 7-hydroxyquinolin-2(1H)-ones synthesis.

    Thakur, Vandna; Sharma, Dharminder; Das, Pralay

    2016-02-01

    Ethyl 3-(2,4-dioxocyclohexyl)propanoate has been explored as a precursor for the synthesis of N-substituted 4,4a,5,6-tetrahydroquinoline-2,7(1H,3H)-diones following conventional protecvtion, selective amidation, and deprotective-cyclization approaches. Moreover, a facile process for the selective dehydrogenative aromatization of these diones was developed to afford the corresponding N-substituted 3,4-dihydro-7-hydroxyquinolin-2(1H)-ones and N-substituted 7-hydroxyquinolin-2(1H)-ones under mild conditions. PMID:26537729

  11. Radiation Parameters of Some Potential Bioactive Compounds.

    Gedik, Zeynep; Tugrak, Mehtap; Dastan, Aysenur; Gul, Halise Inci; Yilmaz, Demet

    2015-06-01

    In this study, we aimed to determine the radiation parameters of some potential bioactive compounds. 1-Aryl-3-dibenzylamino-propane-1-on hydrochloride type Mannich bases were synthesized via classical conventional heating method. Aryl part was changed as phenyl (C6H5), 4-methylphenyl (4-CH3C6H4), 4-fluorophenyl ( 4-FC6H4), 4-nitrophenyl (4-NO2C6H4), 4-chlorophenyl (4-ClC6H4), 4-bromophenyl (4-BrC6H4), and 2-thienyl (C4H3S-2-yl). Mass attenuation coefficient (μm), effective atomic number (Z(eff)) and effective electron density (N(el)) of compounds were determined experimentally and theoretically for at 8.040, 8.910, 13.40, 14.96, 17.48, 19.61, 22.16, 24.94, 32.19, 36.38, 44.48, 50.38 and 59.54 keV photon energies by using an HPGe detector with a resolution of 182 eV at 5.9 keV. Radiation parameters of these compounds which can be anti-cancer drug candidate were given in the tables. The results show that phenyl ring behave like thiophene ring in terms of radiation absorption. It is thought that the results of study may drive allow the development of drug candidate new compounds in medical oncology. PMID:26601355

  12. Synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones and evaluation as antiviral/anti-HIV and anti-tuberculosis agents.

    Kkgzel, Ilkay; Tatar, Esra; Kkgzel, S Gniz; Rollas, Sevim; De Clercq, Erik

    2008-02-01

    As a continuation of our previous efforts on N-alkyl/aryl-N'-[4-(4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thione-5-yl)phenyl]thioureas 1-19 and N-alkyl/aryl-N'-[4-(3-aralkylthio-4-alkyl/aryl-4H-1,2,4-triazole-5-yl)phenyl]thioureas 20-22, a series of novel 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones 23-26 and several related thioureas, N-alkyl/aryl-N'-{4-[(4-alkyl/aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methoxy]phenyl}thioureas 27-42 were synthesized for evaluation of their antiviral potency. Structures of the synthesized compounds were confirmed by the use of (1)H NMR, (13)C NMR and HR-MS data. All compounds 1-42 were evaluated in vitro against HIV-1 (IIIB) and HIV-2 (ROD) strains in MT-4 cells, as well as other selected viruses such as HSV-1, HSV-2, Coxsackie virus B4, Sindbis virus and Varicella-zoster virus using HeLa, Vero, HEL and E6SM cell cultures, and anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv. Compounds 4 and 5 showed weak activity against HSV-1, HSV-2 and TK(-) HSV, whereas eight compounds showed marginal activity against Coxsackie virus B4. The most active derivative in this series was compound 38 which showed moderate protection against Coxsackie virus B4 with an MIC value of 16 microg/ml and a selectivity index of 5. This compound was also active against thymidine kinase positive Varicella-zoster virus (TK(+) VZV, OKA strain) with an EC(50) value of 9.9 microg/ml. Compound 38 was the most active compound with 79% inhibition against M. tuberculosis H37Rv. PMID:17583388

  13. Aryl Diazonium Chemistry for the Surface Functionalization of Glassy Biosensors

    Wei Zheng

    2016-03-01

    Full Text Available Nanostring resonator and fiber-optics-based biosensors are of interest as they offer high sensitivity, real-time measurements and the ability to integrate with electronics. However, these devices are somewhat impaired by issues related to surface modification. Both nanostring resonators and photonic sensors employ glassy materials, which are incompatible with electrochemistry. A surface chemistry approach providing strong and stable adhesion to glassy surfaces is thus required. In this work, a diazonium salt induced aryl film grafting process is employed to modify a novel SiCN glassy material. Sandwich rabbit IgG binding assays are performed on the diazonium treated SiCN surfaces. Fluorescently labelled anti-rabbit IgG and anti-rabbit IgG conjugated gold nanoparticles were used as markers to demonstrate the absorption of anti-rabbit IgG and therefore verify the successful grafting of the aryl film. The results of the experiments support the effectiveness of diazonium chemistry for the surface functionalization of SiCN surfaces. This method is applicable to other types of glassy materials and potentially can be expanded to various nanomechanical and optical biosensors.

  14. Aryl Diazonium Chemistry for the Surface Functionalization of Glassy Biosensors

    Zheng, Wei; van den Hurk, Remko; Cao, Yong; Du, Rongbing; Sun, Xuejun; Wang, Yiyu; McDermott, Mark T.; Evoy, Stephane

    2016-01-01

    Nanostring resonator and fiber-optics-based biosensors are of interest as they offer high sensitivity, real-time measurements and the ability to integrate with electronics. However, these devices are somewhat impaired by issues related to surface modification. Both nanostring resonators and photonic sensors employ glassy materials, which are incompatible with electrochemistry. A surface chemistry approach providing strong and stable adhesion to glassy surfaces is thus required. In this work, a diazonium salt induced aryl film grafting process is employed to modify a novel SiCN glassy material. Sandwich rabbit IgG binding assays are performed on the diazonium treated SiCN surfaces. Fluorescently labelled anti-rabbit IgG and anti-rabbit IgG conjugated gold nanoparticles were used as markers to demonstrate the absorption of anti-rabbit IgG and therefore verify the successful grafting of the aryl film. The results of the experiments support the effectiveness of diazonium chemistry for the surface functionalization of SiCN surfaces. This method is applicable to other types of glassy materials and potentially can be expanded to various nanomechanical and optical biosensors. PMID:26985910

  15. Synthesis and solid state structures of Chalcogenide compounds of Imidazolin-2-ylidene-1,1-Diphenyl-phosphinamine

    Naktode Kishor; Suman Das; Abhinanda Kundu; Hari Pada Nayek; Tarun K Panda

    2016-03-01

    We report the synthesis and solid state structures of 1,3-di-aryl-imidazolin-2-ylidine-1,1-diphenylphosphinamine [(aryl=mesityl (1a) and aryl=2,6-diisopripyl (1b)] and their chalcogenide compounds 3-di-aryl-imidazolin-2-ylidine-P, P-diphenylphosphinicamide (2a,b), 1,3-di-aryl-imidazolin-2-ylidine-P,P diphenyl-phosphinothioicamide (3a,b) and 1,3-diaryl-imidazolin-2-ylidine-P,P -diphenyl-phosphinoselenoicamide (4a,b).The compounds 1a,b were prepared in good yield by the reaction of 1,3-di-aryl-imidazolin-2-imine and chlorodiphenylphosphine in the presence of triethylamine in toluene. The reactions of 1a,b with elemental sulphur and selenium afforded the corresponding chalcogenide compounds 3a,b and 4a,b respectively.The corresponding oxo- derivative (2a,b) was obtained by reacting compound 1a,b with 30% aqueous hydrogen peroxide in THF. The molecular structures of 1a, 2a, 3a and 4a,b have been established by single crystal X-ray diffraction analyses. The molecular structures reveal that even C1–N1–P1 angle (124.62o) in compound 1a is less obtuse compared to the corresponding C1–N1–Si1 angles (157.8o) observed in related N-silylated 2-iminoimidazolines and trimethylsilyl iminophosphoranes. C1–N1–P1 angles are further widened in compounds 2a, 3a, and 4a,b due to the attachment of chalcogen atoms onto phosphorus atom.

  16. Naturally occurring marine brominated indoles are aryl hydrocarbon receptor ligands/agonists.

    DeGroot, Danica E; Franks, Diana G; Higa, Tatsuo; Tanaka, Junichi; Hahn, Mark E; Denison, Michael S

    2015-06-15

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the toxic and biological effects of structurally diverse chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of a larger effort to identify the full spectrum of chemicals that can bind to and activate the AhR, we have examined the ability of several naturally occurring marine-derived brominated indoles and brominated (methylthio)indoles (collectively referred to as brominated indoles) to bind to the AhR and stimulate AhR-dependent gene expression. Incubation of mouse, rat, and guinea pig recombinant cell lines containing a stably transfected AhR-responsive luciferase reporter gene with eight brominated indoles revealed that all compounds stimulated luciferase reporter gene activity, although some species-specific differences were observed. All compounds induced significantly more luciferase activity when incubated with cells for 4 h as compared to 24 h, demonstrating that these compounds are transient activators of the AhR signaling pathway. Three of the brominated indoles induced CYP1A1 mRNA in human HepG2 cells in vitro and Cyp1a mRNA in zebrafish embryos in vivo. The identification of the brominated indoles as direct ligands and activators/agonists of the AhR was confirmed by their ability to compete with [(3)H]TCDD for binding to the AhR and to stimulate AhR transformation and DNA binding in vitro. Taken together, these results indicate that marine-derived brominated indoles are members of a new class of naturally occurring AhR agonists. PMID:26001051

  17. Synthesis and Biological Activity of 3-(2-Furanyl-6-Aryl-1,2,4-Triazolo[3,4-b]-1,3,4 –Thiadiazoles

    Zi-Yi Zhang

    2002-08-01

    Full Text Available 3-(2-Furanyl-4-amino-5-mercapto-1,2,4-triazole (1 was prepared from 2-furoic acid through a multi-step reaction sequence. Compound 1 reacted with aromatic acids in the presence of phosphorus oxychloride to give 3-(2-furanyl-6-aryl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (2. The structures of all the newly synthesized compounds have been confirmed by elemental analysis, IR, 1H-NMR, 13C-NMR and mass spectra. The bioassay indicated most of the title compounds possess significant growth promoting effects on mung bean radicles.

  18. Synthesis and biological studies of some new n-substituted derivatives of n-(1,3-benzodioxol-5-yl)-4-methylbenzenesulfonamide

    Sulfonamides are biologically active compounds with broad spectrum of activities. In the presented research, a small collection of Nalkyl/aralkyl substituted sulfonamides have been synthesized and investigated for inhibition of different bacterial strains. The 1,3 Benzodioxol 5amine (1) was treated with tosyl chloride (2) in water under mild basic conditions to yield the molecule, N(1,3Benzodioxol5yl) 4methylbenzenesulfonamide (3). The target compounds, 5a-i, were obtained by stirring 3 with different electrophiles, 4a-i, in the presence of N,N dimethylformamide and sodium hydride. The structures of the synthesized compounds were established by spectroscopic techniques like IR, 1HNMR and EIMS. These compounds were assayed for their antimicrobial activities via screening against Gram-positive and Gram-negative bacteria. The most of the compounds showed moderate activity against P. aeruginosa relative to reference standard drug, ciprofloxacin. (author)

  19. Preliminary Anticonvulsant and Toxicity Screening of Substituted Benzylidenehydrazinyl-N-(6-substituted benzo[d]thiazol-2-yl)propanamides

    Ruhi Ali; Nadeem Siddiqui

    2014-01-01

    Keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity, a new series of 3-(2-(substitutedbenzylidene)hydrazinyl)-N-(substituted benzo[d]thiazol-2-yl)-propanamides were synthesized with aromatic hydrophobic aryl ring (A), NH–C=O as hydrogen bonding domain (HBD), nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). Synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis...

  20. 6-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors.

    Bromidge, Steven M; Bertani, Barbara; Borriello, Manuela; Faedo, Stefania; Gordon, Laurie J; Granci, Enrica; Hill, Matthew; Marshall, Howard R; Stasi, Luigi P; Zucchelli, Valeria; Merlo, Giancarlo; Vesentini, Alessia; Watson, Jeannette M; Zonzini, Laura

    2008-10-15

    Investigation of a series 6-[2-(4-aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones has led to the discovery of potent 5-HT(1A/1B/1D) receptor antagonists with and without additional SerT affinity. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization. PMID:18799312

  1. 8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors--part II.

    Bromidge, Steven M; Bertani, Barbara; Borriello, Manuela; Bozzoli, Andrea; Faedo, Stefania; Gianotti, Massimo; Gordon, Laurie J; Hill, Matthew; Zucchelli, Valeria; Watson, Jeannette M; Zonzini, Laura

    2009-04-15

    8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones have been identified as highly potent 5-HT(1A/B/D) receptor antagonists with and without additional SerT activity and a high degree of selectivity over hERG potassium channels. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization. PMID:19286377

  2. In vitro microbiological evaluation of 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1-(4H,5H)-diyl))diethanones, novel bisacetylated pyrazoles

    Kanagarajan, Vijayakumar; Ezhilarasi, Muthuvel Ramanathan; Gopalakrishnan, Mannathusamy

    2011-01-01

    Novel 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1-(4H,5H)-diyl))diethanones 7-12 were tested for their antimicrobial activity by disc diffusion and twofold serial dilution method against the tested bacterial and fungal strains. Compounds 7 against Micrococcus luteus, 8 against β-Heamolytic streptococcus, M. luteus, Klebsiella pneumonia, Microsporum gypseum, 9 against Staphylococcus aureus, Shigella flexneri, Vibreo cholerae, Pseudomonas aeruginosa, Aspergillus flavus, Mucor indicus, ...

  3. Principal component analysis for verifying 1H NMR spectral assignments. The case of 3-aryl (1,2,4)-oxadiazole-5-carbohydrazide benzylidene

    The 1H NMR data set of a series of 3-aryl (1,2,4)-oxadiazole-5-carbohydrazide benzylidene derivatives synthesized in our group was analyzed using the chemometric technique of principal component analysis (PCA). Using the original 1H NMR data PCA allowed identifying some misassignments of the proton aromatic chemical shifts. As a consequence of this multivariate analysis, nuclear Overhauser difference experiments were performed to investigate the ambiguity of other assignments of the ortho and meta aromatic hydrogens for the compound with the bromine substituent. The effect of the 1,2,4-oxadiazole group as an electron acceptor, mainly for the hydrogens 12,13, has been highlighted. (author)

  4. Synthesis, characterization and antibacterial activity of some 5-aryl-1, 3-Diphenyl 1-4, 5-dihydro-1H-Pyrazoles

    The condensation of acetophenone (I) with arylaldehyde (II) was investigated and the resulting chalcones 2-Arylidene 1-Acetophenone (III) were reacted with phenyl hydrazine and acetic acid to produce substituted 5-aryl-1, 3-diphenyl-4, 5-dihydro-1H-Pyrazoles (IV). The structures of all products were studied by H-NMR, IR, thermal and elemental analysis. Thermo-gravimetric (TG) and differential thermal analysis (DTA) was applied to investigate the thermal behavior and structure of the synthesized compounds. 2-Pyrazolines (IV) exhibited moderate activity against Streptococcus faecalis ATCC 19433, Klebsiella pneumoniae ATCC 13883, Proteus vulgaris ATCC 25922, Shigella sonnei ATCC 25931 and Peseudom oaeruginosa ATCC 27853. (author)

  5. Synthesis of Benzofuro- and Indolo[3,2-b]indoles via Palladium-Catalyzed Double N-Arylation and Their Physical Properties.

    Truong, Minh Anh; Nakano, Koji

    2015-11-20

    Two kinds of ladder-type π-conjugated compounds, benzofuro[3,2-b]indoles (BFIs) and indolo[3,2-b]indoles (IIs), were successfully synthesized using palladium-catalyzed double N-arylation of anilines with the corresponding dihalobiaryls. Photophysical properties were evaluated by UV-vis and photoluminescence spectroscopies and theoretical calculations. BFI derivatives showed higher quantum yields (33-39%) than the II derivative (29%). The absorption bands of the II derivative were more red-shifted compared to BFI derivatives. PMID:26506120

  6. A study of substituent effects on the NH bond in alkyl and aryl 4,6-disubstituted-3-cyano-2-pyridones

    MILICA MISICVUKOVIC

    2007-12-01

    Full Text Available Substituent effects on the IR stretching frequencies and 1H-NMR chemical shifts of the pyridone NH group in 4- and 6-disubstituted alkyl and aryl 3-cyano-2-pyridones were investigated. The bands most sensitive to substituent effects from the broad and multiple IR NH band for each compound were selected by a computer calculation. The selected values of the IR frequencies and the determined 1H-NMR chemical shifts were subjected to LFER analysis, by correlations with the Hamett ?m/p and SwainLupton F and R substituent constants.

  7. Double N-arylation reaction of polyhalogenated 4,4’-bipyridines. Expedious synthesis of functionalized 2,7-diazacarbazoles

    Mohamed Abboud

    2012-02-01

    Full Text Available Unusual 2,7-diazacarbazoles were prepared in one step from readily available tetra-halogenated 4,4’-bipyridines by using a double N-arylation reaction in the presence of the Pd–XPhos catalyst system. Moderate to good yields were obtained in this site-selective Buchwald–Hartwig double amination. The functionalization of these tricyclic derivatives was performed by using Pd-catalyzed cross-coupling reactions such as the Stille and Suzuki couplings. Two compounds were analyzed by X-ray diffraction and show π–π stacking involving the diazacarbazole moieties and the phenyl rings of functionalized groups.

  8. Rhodium-catalyzed direct ortho C-N bond formation of aromatic azo compounds with azides.

    Wang, Hao; Yu, Yang; Hong, Xiaohu; Tan, Qitao; Xu, Bin

    2014-04-01

    An efficient rhodium-catalyzed regioselective C-N bond formation of azo compounds in good to excellent yields through C-H bond functionalization using azides as the nitrogen source was developed. Alkyl, aryl, and sulfonyl azides could be efficiently assembled in this reaction with excellent functional group tolerance. PMID:24635190

  9. Modification of PEEK model compounds and PEEK film by energetic heavy ion and ultraviolet irradiations

    Ferain, E.; Legras, R.

    1993-10-01

    To prepare nuclear track membranes from poly(aryl ether ether ketone) (PEEK) film, we first determined the modifications induced by heavy ion and UV irradiations in this polymer and two of its model compounds, paraphenoxy benzophenone (PPB) and diphenoxy benzophenone (DPB). This article displays the first results obtained by SEC, HPLC, DSC, FTIR, UV and 13C NMR.

  10. Binding studies using Pichia pastoris expressed human aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator proteins.

    Zheng, Yujuan; Xie, Jinghang; Huang, Xin; Dong, Jin; Park, Miki S; Chan, William K

    2016-06-01

    The aryl hydrocarbon receptor (AHR) is a transcription factor which activates gene transcription by binding to its corresponding enhancer as the heterodimer, which is consisted of AHR and the aryl hydrocarbon receptor nuclear translocator (ARNT). Human AHR can be rather difficult to study, when compared among the AHR of other species, since it is relatively unstable and less sensitive to some ligands in vitro. Overexpression of human AHR has been limited to the baculovirus expression, which is costly and tedious due to the need of repetitive baculovirus production. Here we explored whether we could generate abundant amounts of human AHR and ARNT in a better overexpression system for functional study. We observed that human AHR and ARNT can be expressed in Pichia pastoris with yields that are comparable to the baculovirus system only if their cDNAs are optimized for Pichia expression. Fusion with a c-myc tag at their C-termini seems to increase the expression yield. These Pichia expressed proteins can effectively heterodimerize and form the ternary AHR/ARNT/enhancer complex in the presence of β-naphthoflavone or kynurenine. Limited proteolysis using thermolysin can be used to study the heterodimerization of these human AHR and ARNT proteins. PMID:26923060

  11. A Fluorination/Aryl Migration/Cyclization Cascade for the Metal-Free Synthesis of Fluoro-Benzoxazepines.

    Ulmer, Anna; Brunner, Christoph; Arnold, Andreas M; Pöthig, Alexander; Gulder, Tanja

    2016-03-01

    Fluorinated organic molecules are of high interest for many applications across chemical and medical disciplines. Efficient methods for the synthesis of such compounds are thus needed. Within this work, application of the bench-stable cyclic hypervalent iodine(III) fluoro reagent 1 facilitated the development of an efficient, metal-free method for the preparation of the novel class of 4-fluoro-1,3-benzoxazepines starting from readily available styrenes. The efficacy and broad applicability of this concept is demonstrated by the synthesis of 20 structurally diverse congeners in high yields, regio-, and diastereoselectivities. The presented method provides complementary chemoselectivity when compared to the common, commercially available electrophilic fluorination reagents, such as selectfluor. First mechanistic investigations with isotopically labeled substrates reveal a complex reaction mechanism, proceeding via an unusual fluorination/1,2-aryl migration/cyclization cascade. PMID:26641801

  12. Electronic effects on keto-enol tautomerism of p-substituted aryl-1,3-diketone malonates

    Jimnez-Cruz, Federico; Ros-Olivares, Hector; Garca-Gutirrez, Jos Luis; Mar, Lubanski Fragoza

    2015-12-01

    Electronic effects on keto-enol tautomerism of 1-(p-substituted aryl)-1,3-diketone malonates 1-10 were determined and established by NMR-Hammett linear free energy relationships. In addition, tautomeric equilibrium constants were determined for the title compounds by 1H NMR in DMSO-d6, showing an increasing to diketo tautomer with the increasing in the temperature. In this context, the enol form becomes less stable with increasing temperature suggesting that the intramolecular hydrogen bonding of the cis enol-keto form are increasingly broken at higher temperatures. In general, the enolic form (rather than the keto) is the most stable conformation due to its six member cyclic structure fulfilled by an internal O-H O hydrogen bond.

  13. Enzymatic aryl-O-methyl-14C labeling of model lignin monomers

    Aryl-O-methyl ethers are abundant in aerobic and anaerobic environments. In particular, lignin is composed of units of this type. Lignin monomers specifically radiolabeled in methoxy, side chain, and ring carbons have been synthesized by chemical procedures and are important in studies of lignin synthesis and degradation, humus formation, and microbial O-demethylation. In this paper attention is drawn to an enzymatic procedure for preparing O-methyl-14C-labeled aromatic lignin monomers which has not previously been exploited in microbial ecology and physiology studies and which has several advantages compared with chemical synthesis procedures. O-[methyl-14C]vanillic and O-[methyl-14C]ferulic acids were prepared with S-[methyl-14C]adenosyl-L-methionine as the methyl donor, using commercially obtained porcine liver catechol-O-methyltransferase (EC 2.1.1.6). The specific activity of the methylated products was the same as that of the methyl donor, a maximum of about 58 ?Ci/?mol, and the yields were 42% (vanillate) and 35% (ferulate). Thus lignin monomers are readily prepared as O-methylated products of the catechol-O-methyltransferase reaction and, with this enzyme method of preparation, would be more widely available than labeled compounds which require chemical synthesis

  14. Polymorphism of the aryl-hydrocarbon receptor gene in intron 10 of human cancers

    M. Rocas

    2011-11-01

    Full Text Available Polychlorinated dibenzo-p-dioxins (PCDDs and related halogenated aromatic hydrocarbons (e.g., PCDFs, often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, are among the most toxic synthetic compounds known. The biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR. Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene-coding transactivation domain region (exon 10, intron 10, exon 11 region, previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age. We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA.

  15. Synthesis of -aryl--lactones and relationship: Structure – antifeedant and antifungal activity

    Andrzej Skrobiszewski; Witold Gładkowski; Paulina Walczak; Anna Gliszczyńska; Gabriela Maciejewska; Tomasz Klejdysz; Jan Nawrot; Czesław Wawrzeńczyk

    2015-04-01

    Eighteen racemic -aryl--lactones derived from simple aromatic aldehydes have been obtained in the chemical synthesis. Iodolactones (5c and 6c) were synthesized from ()-4-(benzo[][1′,3′]-dioxol-5′-yl)- but-3-en-2-one (1). Reductive dehalogenation of iodolactones 5a–c and 6a–c afforded -ethyl--lactones (7a–c, 8a–c) whereas the unsaturated lactones (9a–c, 10a–c) were obtained by dehydrohalogenation of iodolactones. All synthesized lactones were fully characterized by spectroscopic data (NMR, IR, HRMS) and subjected to the tests on the antifeedant activity towards Tribolium confusum, Trogoderma granarium and Sitophilus granaries as well to the tests on the antifungal activity towards four Fusarium species. The biological tests allowed to find some relationships between the structure and biological activity of the compounds studied. -Ethyl--lactones 7a–c, 8a–c and unsaturated lactones 9a–c, 10a-c were usually stronger antifeedants than their parent iodolactones 5a–c and 6a–c. trans-Iodolactones 6a–c were more active than cis isomers 5a-c both in antifeedant and antifungal assays. The structure of aromatic substituent was the key factor in antifungal activity. The lactones with benzo [][1,3]dioxole ring (5c, 6c, 7c, 8c, 9c) were the most active whereas those with unsubstituted benzene ring exhibited almost no activity.

  16. Interaction of fish aryl hydrocarbon receptor paralogs (AHR1 and AHR2) with the retinoblastoma protein

    Merson, Rebeka R., E-mail: rmerson@ric.edu [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Biology Department, Rhode Island College, 500 Mt. Pleasant Ave., Providence, RI 02908 (United States); Karchner, Sibel I.; Hahn, Mark E. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

    2009-08-13

    The aryl hydrocarbon receptor (AHR) mediates the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. In some mammalian cell lines, TCDD induces G1 cell cycle arrest, which depends on an interaction between the AHR and the retinoblastoma tumor suppressor (RB). Mammals possess one AHR, whereas fishes possess two or more AHR paralogs that differ in the domains important for AHR-RB interactions in mammals. To test the hypothesis that fish AHR paralogs differ in their ability to interact with RB, we cloned RB cDNA from Atlantic killifish, Fundulus heteroclitus, and studied the interactions of killifish RB protein with killifish AHR1 and AHR2. In coimmunoprecipitation experiments, in vitro-expressed killifish RB coprecipitated with both AHR1 and AHR2. Consistent with these results, both killifish AHR1 and AHR2 interacted with RB in mammalian two-hybrid assays. These results suggest that both fish AHR1 and AHR2 paralogs may have the potential to influence cell proliferation through interactions with RB.

  17. Ligand independent aryl hydrocarbon receptor inhibits lung cancer cell invasion by degradation of Smad4.

    Lee, Chen-Chen; Yang, Wen-Hao; Li, Ching-Hao; Cheng, Yu-Wen; Tsai, Chi-Hao; Kang, Jaw-Jou

    2016-07-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Although AhR plays a crucial role in air toxicant-induced carcinogenesis, AhR expression was shown to negatively regulate tumorigenesis. Therefore, in the present study, we investigated the effect of AhR without ligand treatment on cancer invasion in lung cancer cell lines. Lung cancer cells expressing lower levels of AhR showed higher invasion ability (H1299 cells) compared with cells expressing higher levels of AhR (A549 cells). Overexpression of AhR in H1299 cells inhibited the invasion ability. We found that vimentin expression was inhibited in AhR-overexpressing H1299 cells. Additionally, the expression of EMT-related transcriptional factors Snail and ID-1 decreased. Interestingly, we found that Smad4 degradation was induced in AhR-overexpressing H1299 cells. Our data showed that AhR could interact with Jun-activation domain binding protein (Jab1) and Smad4, which may cause degradation of Smad4 by the proteasome. Our data suggest that AhR affects the transforming growth factor-β signaling pathway by inducing Smad4 degradation by the proteasome and suppressing tumor metastasis via epithelial to mesenchymal transition reduction in lung cancer cells. PMID:27060206

  18. Cigarette smoke condensate induces aryl hydrocarbon receptor-dependent changes in gene expression in spermatocytes.

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Moley, Kelle H

    2012-12-01

    Cigarette smoke contains numerous compounds that cause oxidative stress and alter gene expression in many tissues, and cigarette smoking is correlated with male infertility. To identify mechanisms by which this occurs, we evaluated expression of antioxidant genes in mouse spermatocytes in response to cigarette smoke condensate (CSC). CSC exposure led to oxidative stress and dose-dependent up-regulation of Hsp90aa1, Ahr, Arnt, Sod1, Sod2, and Cyp1a1 expression in a mouse spermatocyte cell line. An antagonist of the aryl hydrocarbon receptor (AHR) abrogated several CSC-mediated changes in mRNA and protein levels. Consistent with these results, spermatocytes isolated by laser-capture microdissection from CSC-treated mice showed increased expression of several antioxidant genes. In vivo exposure to CSC was genotoxic to spermatocytes, resulting in apoptosis and disruptions to the seminiferous tubules. Our in vivo and in vitro data indicate that CSC-mediated damage to murine spermatocytes is AHR-dependent and is mediated by oxidative stress. PMID:23069111

  19. Structural investigation of HIV-1 nonnucleoside reverse transcriptase inhibitors: 2-Aryl-substituted benzimidazoles

    Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

    2009-11-01

    Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is one of the most destructive epidemics in history. Inhibitors of HIV enzymes are the main targets to develop drugs against that disease. Nonnucleoside reverse transcriptase inhibitors of HIV-1 (NNRTIs) are potentially effective and nontoxic. Structural studies provide information necessary to design more active compounds. The crystal structures of four NNRTI derivatives of 2-aryl-substituted N-benzyl-benzimidazole are presented here. Analysis of the geometrical parameters shows that the structures of the investigated inhibitors are rigid. The important geometrical parameter is the dihedral angle between the planes of the π-electron systems of the benzymidazole and benzyl moieties. The values of these dihedral angles are in a narrow range for all investigated inhibitors. There is no significant difference between the structure of the free inhibitor and the inhibitor in the complex with RT HIV-1. X-ray structures of the investigated inhibitors are a good basis for modeling enzyme-inhibitor interactions in rational drug design.

  20. Enantiomeric separations of α-aryl ketones with cyclofructan chiral stationary phases via high performance liquid chromatography and supercritical fluid chromatography.

    Breitbach, Anthony S; Lim, Yeeun; Xu, Qing-Long; Kürti, László; Armstrong, Daniel W; Breitbach, Zachary S

    2016-01-01

    Normal phase chiral HPLC and SFC methods are presented for the enantiomeric separation of 21 α-aryl ketones with a unique class of chiral stationary phases (CSPs) based on cyclofructans (CFs). Separations were achieved for all but 2 analytes, with 17 compounds attaining baseline separation having resolution values up to 4.0. Most separations obtained in HPLC could be transferred to SFC, but the HPLC resolutions were generally better due to greater enantiomeric selectivity values. A structure-separation relationship (SSR) was developed to identify important structural features for separation of this class of compounds using CF-based CSPs. Preliminary studies are also presented that demonstrate the utility of the CF CSPs to investigate the base-induced enantiomerization of α-aryl ketones. It was demonstrated that even small amounts of base (0.01%v/v) in the mobile phase results in rapid, on-column, enantiomerization. Lastly, CSPs composed of superficially porous particles were used to achieve comparable separations of this class of chiral compounds, but at a fraction of the analysis time compared to CSPs composed of fully porous particles. PMID:26687164

  1. Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action.

    Tan, Fangfang; Shi, Baojun; Li, Jian; Wu, Wenjun; Zhang, Jiwen

    2015-01-01

    Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that the compounds (S)-2-(2'-hydroxyphenyl)-4-hydroxy-methyl- 4,5-dihydrothiazole (7h) and (R)-2-(2'-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydro-thiazole (7h') exhibited significant inhibition against Ralstonia solanacearum, Pseudomonas syringae pv. actinidiae, Bacillus subtilis and Bacillus cereus, with minimum inhibitory concentrations (MICs) ranging from 3.91 to 31.24 μg·mL(-1). The effect of substituents showed that not only electron-withdrawing groups, but also electron-donating groups could abolish the antibacterial activities unless a 2'-hydroxy group was introduced on the 2-aryl substituent of the 4,5-dihydrothiazole analogues. The results of scanning electron microscope (SEM) and fatty acid exposure experiments indicated that these antibacterial compounds influence fatty acid synthesis in the tested bacteria. PMID:26569197

  2. Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action

    Fangfang Tan

    2015-11-01

    Full Text Available Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that the compounds (S-2-(2′-hydroxyphenyl-4-hydroxy-methyl- 4,5-dihydrothiazole (7h and (R-2-(2′-hydroxyphenyl-4-hydroxymethyl-4,5-dihydro-thiazole (7h′ exhibited significant inhibition against Ralstonia solanacearum, Pseudomonas syringae pv. actinidiae, Bacillus subtilis and Bacillus cereus, with minimum inhibitory concentrations (MICs ranging from 3.91 to 31.24 μg·mL−1. The effect of substituents showed that not only electron-withdrawing groups, but also electron-donating groups could abolish the antibacterial activities unless a 2′-hydroxy group was introduced on the 2-aryl substituent of the 4,5-dihydrothiazole analogues. The results of scanning electron microscope (SEM and fatty acid exposure experiments indicated that these antibacterial compounds influence fatty acid synthesis in the tested bacteria.

  3. Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

    Paul Knochel

    2011-09-01

    Full Text Available In this review we summarize the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein. Experimental details are given for the most important reactions in the Supporting Information of this article.

  4. Synthesis and Antimicrobial Activity of N-Substituted-?-amino Acid Derivatives Containing 2-Hydroxyphenyl, Benzo[b]phenoxazine and Quinoxaline Moieties

    Kristina Mickevi?ien?

    2015-02-01

    Full Text Available 3-[(2-Hydroxyphenylamino]butanoic and 3-[(2-hydroxy-5-methyl(chlorophenylamino]butanoic acids were converted to a series of derivatives containing hydrazide, pyrrole and chloroquinoxaline moieties. The corresponding benzo[b]phenoxazine derivatives were synthesized by the reaction of the obtained compounds with 2,3-dichloro-1,4-naphthoquinone. Five of the synthesized compounds exhibited good antimicrobial activity against Staphylococcus aureus and Mycobacterium luteum, whereas three compounds showed significant antifungal activity against Candida tenuis and Aspergillus niger.

  5. Enantioselective cross-coupling of meso-epoxides with aryl halides.

    Zhao, Yang; Weix, Daniel J

    2015-03-11

    The first enantioselective cross-electrophile coupling of aryl bromides with meso-epoxides to form trans-β-arylcycloalkanols is presented. The reaction is catalyzed by a combination of (bpy)NiCl2 and a chiral titanocene under reducing conditions. Yields range from 57 to 99% with 78-95% enantiomeric excess. The 30 examples include a variety of functional groups (ether, ester, ketone, nitrile, ketal, trifluoromethyl, sulfonamide, sulfonate ester), both aryl and vinyl halides, and five- to seven-membered rings. The intermediacy of a carbon radical is strongly suggested by the conversion of cyclooctene monoxide to an aryl [3.3.0]bicyclooctanol. PMID:25716775

  6. Well-Defined Copper(I) Fluoroalkoxide Complexes for Trifluoroethoxylation of Aryl and Heteroaryl Bromides

    Huang, Ronglu

    2015-03-17

    © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Copper(I) fluoroalkoxide complexes bearing dinitrogen ligands were synthesized and the structure and reactivity of the complexes toward trifluoroethoxylation, pentafluoropropoxylation, and tetrafluoropropoxylation of aryl and heteroaryl bromides were investigated. Efficiency drive: A series of copper(I) fluoroalkoxide complexes bearing N,N ligands have been prepared and structurally characterized. These well-defined complexes serve as efficient reagents for the fluoroalkoxylation of aryl and heteroaryl bromides to produce a wide range of trifluoroethyl, pentafluoropropyl, and tetrafluoropropyl (hetero)aryl ethers in good to excellent yields.

  7. Reactivity of Aryl Halides for Reductive Dehalogenation in (Seawater Using Polymer-Supported Terpyridine Palladium Catalyst

    Toshimasa Suzuka

    2015-05-01

    Full Text Available A polymer-supported terpyridine palladium complex was prepared. The complex was found to promote hydrodechlorination of aryl chlorides with potassium formate in seawater. Generally, reductive cleavage of aryl chlorides using transition metal catalysts is more difficult than that of aryl bromides and iodides (reactivity: I > Br > Cl; however, the results obtained did not follow the general trend. Therefore, we investigated the reaction inhibition agents and found a method to remove these inhibitors. The polymeric catalysts showed high catalytic activity and high reusability for transfer reduction in seawater.

  8. Synthesis, biological activity evaluation and molecular docking studies of novel coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes.

    Vaarla, Krishnaiah; Kesharwani, Rajesh Kumar; Santosh, Karnewar; Vedula, Rajeswar Rao; Kotamraju, Srigiridhar; Toopurani, Murali Krishna

    2015-12-15

    A novel series of coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes (4a-o) were synthesized via an efficient, one-pot multicomponent approach involving 3-(2-bromoacetyl)coumarins (1a-g), thiosemicarbazide (2) and substituted acetophenones (3a-c) utilizing Vilsmeier-Haack reaction condition with good yields. The title compounds structure was elucidated by spectroscopic data (IR, NMR and Mass) and elemental analysis. All the synthesized compounds were screened for their in vitro cytotoxic activity against MCF-7, DU-145 and HeLa cell lines and studied detailed about molecular interaction of probable target protein human microsomal cytochrome CYP450 2A6 using docking simulation. These coumarin derivatives were exhibiting moderate to appreciable cytotoxic activities. The compounds 4m and 4n exhibited significant cytotoxic activity with IC50 values having 5.75 and 6.25?M against HeLa cell line. Similarly compound 4n also exhibiting good anti cancer property and antibacterial activity against DU-145 cell line and Gram negative bacterial strains. PMID:26542964

  9. Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles.

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Wadood, Abdul; Rahim, Fazal; Saad, Syed Muhammad; Khan, Khalid Mohammed; Nasir, Abdul

    2016-06-01

    Twenty derivatives of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles (1-20) were synthesized and evaluated for their α-glucosidase inhibitory activities. Compounds containing hydroxyl and halogens (1-6, and 8-18) were found to be five to seventy folds more active with IC50 values in the range of 12.75±0.10-162.05±1.65μM, in comparison with the standard drug, acarbose (IC50=856.45±5.60μM). Current study explores the α-glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction. PMID:27149363

  10. Novel fluorescent 1,8-naphthalimide derivatives containing thiophene and pyrazole moieties: Synthesis by direct C-H arylation and evaluation of photophysical and electrochemical properties

    Jin, Zhengneng; Wu, Jiashou; Wang, Chuanfeng; Dai, Guoliang; Liu, Shiyong; Lu, Jianmei; Jiang, Huajiang

    2014-01-01

    A series of novel 1,8-naphthalimide derivatives containing thiophene and pyrazole moities were synthesized by direct Pd-catalyzed C-H arylation and then characterized by 1H NMR, 13C NMR, MALDI-HRMS, and elementary analysis. The photophysical and electrochemical properties of the derivatives were also investigated. All compounds have green emission both in diluted CH2Cl2 solution and solid film. The cyclic voltammetry (CV) measurements showed that the target compounds had a lowest unoccupied molecular orbital (LUMO) range from -3.49 eV to -3.29 eV and a highest occupied molecular orbital (HOMO) range from -6.04 eV to -5.81 eV. Quantum chemical calculations were performed to obtain the optimized ground-state geometry as well as the spatial distributions of the HOMO, LUMO levels of the compounds.

  11. Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis

    Nguyen, Nam Trung; Nakahama, Taisuke; Nguyen, Chi Hung; Tran, Trang Thu; Le, Van Son; Chu, Hoang Ha; Kishimoto, Tadamitsu

    2015-01-01

    Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen-induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes. Consistent with these findings, several Ahr antagonists such as α-naphthoflavone, resveratrol, and GNF351 reverse the effect of Ahr ligands in RA pathogenesis. In this review, we summarize the current knowledge of Ahr function in the immune system and the potential clinical benefits of Ahr antagonism in treating RA.

  12. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  13. Chain-extended poly(aryl ether ketones)

    Robeson, L.M.; Winslow, P.A.; Matzner, M.; Harris, J.E.; Maresca, L.M.

    1992-06-09

    This patent describes a process for preparing a poly(aryl ether ketone) polymer. It comprises reacting (n) moles of HAr H with (n + 1) moles of YCOAr{sub 1}COY under Friedel-Crafts polymerization conditions; reacting the product obtained with 2XAR{sub 2}H under Friedel-Crafts polymerization conditions; reacting the product obtained with HOAr{sub 3}OH in the presence of a base and an aprotic solvent; wherein Ar and Ar{sub 1} are divalent aromatic groups, Ar{sub 2} is a divalent aromatic group wherein the substituents X and CO are in para or ortho position relative to each other, Ar{sub 3} is a residue of a dihydric phenol, X and Y are halogen, n is an integer of 1 to 50 and X is one or greater.

  14. Fluorescence characteristics of aryl boronic acid derivate (PBA)

    Patil, S. S.; Muddapur, G. V.; Patil, N. R.; Melavanki, R. M.; Kusanur, R. A.

    2015-03-01

    The absorption and fluorescence spectra of newly synthesized aryl boronic acid derivative namely Phenyl boronic acid (PBA) have been recorded in various solvents of different polarities. The ground state dipole moment of PBA was obtained from quantum chemical calculations. Solvatochromic correlations were used to estimate the ground state (μg) and excited state (μe) dipole moments. The excited state dipole moments are observed to be greater than the ground state dipole moments. Further, the ground and excited state dipole moments are not parallel but subtend by an angle of 70°. The changes in dipole moment (Δμ) were calculated both from solvatochromic shift method and microscopic solvent polarity parameter (ETN), and the values are compared. Solvent effects on the absorption and fluorescence spectra were quantified using Reichardt's and bulk solvent polarity parameters were complemented by the results of the Kamlet-Taft treatment.

  15. Selective transformations of substituted aryl compounds to fluorenes and phosphoramidates : synthetic and spectroscopic studies

    Haggam, Reda

    2010-01-01

    Because of their diverse biological properties and their high potential for the development of new drugs the synthesis of fluorenes and related systems such as benzo[b]fluorenes is of great interest in the fields of organic and medicinal chemistry. The most relevant benzo[b]fluorenes include the naturally occurring kinamycins. Recently, two fluorene derivatives have been isolated from the sweat of hippopotamus (Hippopotamus amphibius). The biological function of the two dyes named hipposudori...

  16. Recent Developments of C-Aryl Glucoside SGLT2 Inhibitors.

    Zhang, Yang; Liu, Zhao-Peng

    2016-03-16

    Sodium-glucose cotransporter 2 (SGLT2) is almost exclusively expressed in the proximal renal tubules. It is responsible for about 90% of the glucose reabsorption from tubular fluid. Selective inhibition of SGLT2 is expected to favor in the normalization of plasma glucose levels in T2DM patients through the prevention of renal glucose reabsorption and the promotion of glucose excretion from urine. Selective SGLT2 inhibitors have the merits to minimize the gastrointestinal side effects associated with SGLT1 inhibition, and selective SGLT2 inhibition may have a low risk of hypoglycemia. Since the C-aryl glucosides are metabolically more stable than the O-glucosides, numerous efforts have been made in the development of potent and selective C-aryl glucoside SGLT2 inhibitors, and a number of them are now used as anti-diabetes drugs in clinic or at various stages of clinical developments. Based on their structural features, in this review, these SGLT2 inhibitors are classified as three types: the phenyl/arylmethylphenyl C-glucosides, with an emphasis on the modifications on the proximal and/or the distal phenyl ring, and the spacer; the heteroarylmethylphenyl Cglucosides, with a replacement of the distal phenyl ring by a heterocycle like pyridazine, pyrimidine, thiophene and benzothiophene, thiazole, 1,3,4-thiadiazole, and triazolopyridinone; and the glucose-modified Caryl glucosides, including the glucose C-1 derived O-spiroketals, C-4 gem-difluoro analogues, C-5 and C-6 modified derivatives, dioxa-bicyclo[3.2.1]octane bridged ketals, the thioglucosides, and carbasugars. The structure-activity relationships (SARs) of each type along with their inhibitory potency against human SGLT2 and selectivity over human SGLT1 are discussed. PMID:26861002

  17. Phosphine-free palladium-catalyzed direct bisarylation of pyrroles with aryl iodides on water.

    Cho, Beom Shin; Bae, Hyun Jung; Chung, Young Keun

    2015-05-15

    The Pd-catalyzed bisarylation of pyrroles with aryl iodides on water is described. The reaction proceeds under mild reaction conditions, i.e., relatively low temperature (40 °C) and phosphine-free. PMID:25919427

  18. Synthesis of N-Substituted Derivatives of N-(4-(N- (5-Chloro-2 methoxyphenyl)sulfamoyl)phenyl)acetamide with potential antiurease activity

    In this study, a new series of N-alkyl/arakyl derivatives of N-(4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)phenyl)acetamide (5a-k) was synthesized and screened for enzyme inhibition activity. Target compounds, N-alkyl/arakyl sulfamoylacetamides (5a-k) were synthesized by stirring N-(4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)phenyl)acetamide (3) with different electrophiles (4a-k) in the presence of sodium hydride (NaH) and N, N-dimethylformamide (DMF). The structures of all the synthesized compounds have been deduced from their spectral (1H-NMR, IR, EI-MS) data. All the new compounds displayed antiurease activity to varying degree. (author)

  19. Enantioselective Cross-Coupling of meso-Epoxides with Aryl Halides

    Zhao, Yang; Weix, Daniel J.

    2015-01-01

    The first enantioselective cross-electrophile coupling of aryl bromides with meso-epoxides to form trans-β-arylcycloalkanols is presented. The reaction is catalyzed by a combination of (bpy)NiCl2 and a chiral titanocene under reducing conditions. Yields range from 57 to 99% with 78–95% enantiomeric excess. The 30 examples include a variety of functional groups (ether, ester, ketone, nitrile, ketal, trifluoromethyl, sulfonamide, sulfonate ester), both aryl and vinyl halides, and five- to seven...

  20. Synthesis and preliminary evaluation of antinociceptive activity of novel isoxazolyl-aryl-hydrazones

    New 2-isoxazoline aldehydes were synthesized, in good yields, from cycloadduct of the 1,3-dipolar cycloaddition reaction between endocyclic enecarbamate and carboethoxyformonitrile oxide (CEFNO). Condensation of these 2-isoxazoline aldehydes with several phenyl-hydrazines produced new isoxazolyl-aryl-hydrazones, which showed low toxicity and excellent antinociceptive activity, when compared to dipyrone. The antinociceptive activity of isoxazolyl-aryl-hydrazones was performed using the acetic acid-induced mice abdominal constrictions test. (author)

  1. Copper-Catalyzed [18F]Fluorination of (Mesityl)(aryl)iodonium Salts

    Ichiishi, Naoko; Brooks, Allen F.; Topczewski, Joseph J.; Rodnick, Melissa E.; Sanford, Melanie S.; Scott, Peter J.H.

    2014-01-01

    A practical, rapid, and highly regioselective Cu-catalyzed radiofluorination of (mesityl)(aryl)iodonium salts is described. This protocol utilizes [18F]KF to access 18F-labeled electron-rich, -neutral, and -deficient aryl fluorides under a single set of mild conditions. This methodology is applied to the synthesis of protected versions of two important radiotracers: 4-[18F]fluorophenylalanine and 6-[18F]fluoroDOPA.

  2. An air-stable copper reagent for nucleophilic trifluoromethylthiolation of aryl halides

    Weng, Zhiqiang

    2012-12-12

    A series of copper(I) trifluoromethyl thiolate complexes have been synthesized from the reaction of CuF2 with Me3SiCF 3 and S8 (see scheme; Cu red, F green, N blue, S yellow). These air-stable complexes serve as reagents for the efficient conversion of a wide range of aryl halides into the corresponding aryl trifluoromethyl thioethers in excellent yields. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Reduction of sulphur from polysulphidic model compounds by the hyperthermophilic archaebacterium pyrococcus furiosus

    Tilstra, L.; Eng, G.; Olson, G.J.; Wang, F.W. (National Institute of Standards and Technology, Gaithersburg, MD (USA). Polymer Science Division)

    1992-07-01

    Several polysulphidic model compounds were studied for their reducibility by a hyperthermophilic archaebacterium, {ital Pyrococcus furiosus}. Model compounds that may represent forms of organic sulphur in coal were selected for study including model compounds with bulky alkyl and aryl groups surrounding the sulphur atoms and polymeric polysulphides. {ital P. furiosus} reduced these organic polysulphides to hydrogen sulphide with varying efficiency. The use of complex model compounds may be more realistic than simple model compounds for evaluating the potential for microbial removal of organic sulphur from coal. 17 refs., 1 fig., 3 tabs.

  4. ULTRASOUND ASSISTED EFFICIENT AND GREENER ONE POT SYNTHESIS OF ARYL-14-H-DIBENZO [a,j]XANTHENE DERIVATIVES Ultraschall unterstützt effizientere und umweltfreundlichere ONE Eintopfsynthese ARYL-14-H-dibenzo [a, j] Xanthenderivate

    Saurabh Puri, Balbir Kaur, Anupama Parmar and Harish Kumar

    2011-01-01

    Aryl-14-H-dibenzo[a,j]xanthenes have been synthesized in high yields from the condensation of aryl aldehydes and 2-napthol in presence of copper perchlorate hexahydrate as catalyst at room temperature gives aryl-14-H-dibenzo[a,j]xanthenes with excellent yields under ultrasound irradiation (35 kHz). This method has the advantages of high yield, simple methodology, greener and one pot procedure.

  5. ULTRASOUND ASSISTED EFFICIENT AND GREENER ONE POT SYNTHESIS OF ARYL-14-H-DIBENZO [a,j]XANTHENE DERIVATIVES Ultraschall unterstützt effizientere und umweltfreundlichere ONE Eintopfsynthese ARYL-14-H-dibenzo [a, j] Xanthenderivate

    Saurabh Puri, Balbir Kaur, Anupama Parmar and Harish Kumar

    2011-07-01

    Full Text Available Aryl-14-H-dibenzo[a,j]xanthenes have been synthesized in high yields from the condensation of aryl aldehydes and 2-napthol in presence of copper perchlorate hexahydrate as catalyst at room temperature gives aryl-14-H-dibenzo[a,j]xanthenes with excellent yields under ultrasound irradiation (35 kHz. This method has the advantages of high yield, simple methodology, greener and one pot procedure.

  6. Synthesis, Density Functional Theory (DFT, Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties

    Mnaza Noreen

    2015-11-01

    Full Text Available A variety of novel 5-aryl thiophenes 4a–g containing sulphonylacetamide (sulfacetamide groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT studies were performed using the B3LYP/6-31G (d, p basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs analysis of all compounds 4a–g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response were simulated at the B3LYP/6-31G (d, p level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenylthiophen-2-ylsulfonyl acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 ± 0.11 at 15 µg/mL with IC50 17.1 µg/mL. Moreover, some other compounds 4a–f also exhibited very good inhibition against urease enzyme.

  7. Synthesis and NMR Studies of (E)-1-Aryl-3-(2-pyrrolyl)-2-propenones and (E)-3-Aryl-1-(2-pyrrolyl)-2-propenones

    Lee, Insook; Jeoung, Eun Ji; Lee, Chang Kiu [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2013-03-15

    Series of (E)-1-aryl-3-(2-pyrrolyl)-2-propenones, that were aldol condensation products between pyrrole-2-carbaldehyde and m- and p-substituted acetophenones, were prepared and their {sup 1}H and {sup 13}C NMR spectra were examined to obtain the information on the conformation of the enone system. Similar studies were carried out with (E)-3-aryl-1-(2-pyrrolyl)-2-propenones that were prepared from 2-acetylpyrrole and m- and p-substituted benzaldehydes. The substituent chemical shifts were studied by applying the Hammett relationship.

  8. Selective C-Arylation of 2,5-Dibromo-3-hexylthiophene via Suzuki Cross Coupling Reaction and Their Pharmacological Aspects

    Hafiz Mansoor Ikram

    2015-03-01

    Full Text Available The present study reports the synthesis of various new derivatives based on 5-aryl-2-bromo-3-hexylthiophene with moderate-to-good yields via a palladium-catalyzed Suzuki cross-coupling reaction. This coupling method involved the reaction of 2,5-dibromo-3-hexylthiophene with several arylboronic acids in order to synthesize corresponding thiophene derivatives under controlled and optimal reaction conditions. The different substituents (CH3, OCH3, Cl, F etc. present on arylboronic acids are found to have significant electronic effects on the overall properties of new products. The synthesized thiophene molecules were studied for their haemolytic, biofilm inhibition and anti-thrombolytic activities, and almost all products showed potentially good properties. The compound 2-bromo-5-(3-chloro-4-fluorophenyl-3-hexylthiophenein particular exhibited the highest values for haemolytic and bio-film inhibition activities among all newly synthesized derivatives. In addition, the compound 2-bromo-3-hexyl-5-(4-iodophenylthiophene also showed high anti-thrombolytic activity, suggesting the potential medicinal applications of these newly synthesized compounds.

  9. Binding model construction of antifungal 2-aryl-4-chromanones using CoMFA, CoMSIA, and QSAR analyses.

    Wei, Deng-Guo; Yang, Guang-Fu; Wan, Jian; Zhan, Chang-Guo

    2005-03-01

    Flavonoids, generated by plants upon attack by a range of pathogens, are demonstrated to have a role in biotic and abiotic stress response phenomena in plants, and there is increasing evidence for the antibacterial, antifungal, and antiviral activities of these compounds. Using the bioisosterism strategy, a series of 2-aryl-4-chromanone derivatives based upon the structure of flavanones, a kind of flavonoid phytoalexins, were synthesized and tested for the antifungal activity against Pyricularia grisea, which have been reported in our previous papers. To further explore the comprehensive structure-activity relationship and construct the binding model for the antifungal compounds, two kinds of molecular field analysis techniques, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), were performed following a Hansch-Fujita QSAR study. Superimpositions were performed using three alignment rules, that is, centroid-based alignment, common substructure-based alignment, and field fit alignment, and statistically reliable models with good predictive power (CoMFA r(2) = 0.952, q(2) = 0.727; CoMSIA r(2) = 0.965, q(2) = 0.751) were achieved on the basis of the common substructure-based alignment. The combined results of CoMFA, CoMSIA, and former Hansch-Fujita QSAR analyses resulted in comprehensive understanding about the structure-activity relationships, which led to this construction of a plausible binding model of the title compounds. PMID:15740047

  10. Nickel-catalyzed vinylation of aryl chlorides and bromides with vinyl ZnBr.MgBrCl.

    Yamamoto, Tetsuya; Yamakawa, Tetsu

    2009-05-01

    The Ni-catalyzed cross-coupling of aryl halides and vinylzinc bromide for the synthesis of styrene derivatives was investigated. Of the catalysts surveyed, the combination of Ni(acac)(2) and Xantphos was found to be the most effective for this cross-coupling. This catalyst could be used in reactions with various aryl bromides and chlorides, including electron-rich aryl chlorides such as chloroanisoles. PMID:19354270

  11. Copper oxide nanoparticle-catalyzed coupling of diaryl diselenide with aryl halides under ligand-free conditions.

    Reddy, Vutukuri Prakash; Kumar, Akkilagunta Vijay; Swapna, Kokkirala; Rao, Kakulapati Rama

    2009-02-19

    A new, efficient and ligand-free cross-coupling reaction of aryl halides and diaryl diselenides using a catalytic amount of nanocrystalline CuO as a recyclable catalyst with KOH as the base in DMSO at 110 degrees C is reported. This protocol has been utilized for the synthesis of a variety of aryl selenides in excellent yields from the readily available aryl halides and diaryl diselenides. PMID:19182886

  12. Síntese de beta-N-acetilglicosaminídeos de arila modificados em C-6 como potenciais agentes antimicrobianos Synthesis of aryl beta-N-acetylglucosaminedes modified at C-6 as potential antimicrovial agents

    Rozângela Magalhães Manfrini

    2008-01-01

    Full Text Available We report herein the synthesis of aryl beta-N-acetylglucosaminides containing azido, amino and acetamido groups at C-6 as potential antimicrobial agents. It was expected that these compounds could interfere with the biosynthesis and/or biotransformation of N-acetylglucosamine in fungi and bacteria. None of the compounds showed antimicrobial activity against bacteria (Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, filamentous fungus (Aspergillus niger and yeasts (Saccharomyces cerevisae, Candida albicans and Candida tropicallis, at the concentration of 1 mg/mL in agar diffusion assay.

  13. Synthesis of aryl b-N-acetylglucosamine desmodified at C-6 as potential antimicrobial agents; Sintese de b-N-acetilglicosaminideos de arila modificados em C-6 como potenciais agentes antimicrobianos

    Manfrini, Rozangela Magalhaes; Souza Filho, Jose Dias de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Exatas; Figueireido, Rute Cunha; D' Angelis, Allison Fabiano; Prado, Maria Auxiliadora Fontes; Nunan, Elziria de Aguiar; Martins, Gabriela Aires; Alves, Ricardo Jose [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Dept. de Produtos Farmaceuticos]. E-mail: ricardodylan@farmacia.ufmg.br

    2008-07-01

    We report herein the synthesis of aryl beta-N-acetylglucosaminides containing azido, amino and acetamido groups at C-6 as potential antimicrobial agents. It was expected that these compounds could interfere with the biosynthesis and/or biotransformation of Nacetylglucosamine in fungi and bacteria. None of the compounds showed antimicrobial activity against bacteria (Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa), filamentous fungus (Aspergillus niger) and yeasts (Saccharomyces cerevisae, Candida albicans and Candida tropicallis), at the concentration of 1 mg/mL in agar diffusion assay. (author)

  14. Sntese de beta-N-acetilglicosamindeos de arila modificados em C-6 como potenciais agentes antimicrobianos / Synthesis of aryl beta-N-acetylglucosaminedes modified at C-6 as potential antimicrovial agents

    Rozngela Magalhes, Manfrini; Jos Dias de, Souza Filho; Rute Cunha, Figueiredo; Allison Fabiano, D' Angelis; Maria Auxiliadora Fontes, Prado; Elzria de Aguiar, Nunan; Gabriela Aires, Martins; Ricardo Jos, Alves.

    Full Text Available [...] Abstract in english We report herein the synthesis of aryl beta-N-acetylglucosaminides containing azido, amino and acetamido groups at C-6 as potential antimicrobial agents. It was expected that these compounds could interfere with the biosynthesis and/or biotransformation of N-acetylglucosamine in fungi and bacteria. [...] None of the compounds showed antimicrobial activity against bacteria (Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa), filamentous fungus (Aspergillus niger) and yeasts (Saccharomyces cerevisae, Candida albicans and Candida tropicallis), at the concentration of 1 mg/mL in agar diffusion assay.

  15. Synthesis and in vitro antimicrobial evaluation of 5-amino-7-aryl-6-cyano-4H- pyrano[3,2,b]pyrrole derivatives catalyzed by reusable ZrOCl28H2O

    A. Mohammed Hussain

    2014-01-01

    Full Text Available An efficient synthesis of a new series of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole derivatives from the reaction of 3-hydroxypyrrole, malononitrile, and various aromatic aldehydes using ZrOCl28H2O, an environmentally friendly catalyst under a thermal solvent-free green procedure is described. This simple protocol offer advantages such as shorter reaction times, simple work-up and excellent yield. The catalyst ZrOCl28H2O can be reused. The reusability of the catalyst has been studied for the synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole. All the compounds were screened for their antibacterial and antifungal activity. DOI:http://dx.doi.org/10.4314/bcse.v28i1.11

  16. Design and synthesis of a C7-aryl piperlongumine derivative with potent antimicrotubule and mutant p53-reactivating properties.

    Punganuru, Surendra R; Madala, Hanumantha Rao; Venugopal, Sanjay N; Samala, Ramakrishna; Mikelis, Constantinos; Srivenugopal, Kalkunte S

    2016-01-01

    Small molecules that can restore biological function to the p53 mutants found in human cancers have been highly sought to increase the anticancer efficacy. In efforts to generate hybrid anticancer drugs that can impact two or more targets simultaneously, we designed and developed piperlongumine (PL) derivatives with an aryl group inserted at the C-7 position. This insertion bestowed a combretastatin A4 (CA4, an established microtubule disruptor) like structure while retaining the piperlongumine configuration. The new compounds exhibited potent antiproliferative activities against eight cancer cell lines, in particular, were more cytotoxic against the SKBR-3 breast cancer cells which harbor a R175H mutation in p53 suppressor. KSS-9, a representative aryl PL chosen for further studies induced abundant ROS generation and protein glutathionylation. KSS-9 strongly disrupted the tubulin polymerization in vitro, destabilized the microtubules in cells and induced a potent G2/M cell cycle block. More interestingly, KSS-9 showed the ability to reactivate the p53 mutation and restore biological activity to the R175H mutant protein present in SKBR3 cells. Several procedures, including immunocytochemistry using conformation-specific antibodies for p53, immunoprecipitation combined with western blotting, electrophoretic shift mobility shift assays showed a reciprocal loss of mutant protein and generation of wild-type like protein. p53 reactivation was accompanied by the induction of the target genes, MDM2, p21cip1 and PUMA. Mechanistically, the redox-perturbation in cancer cells by the hybrid drug appears to underlie the p53 reactivation process. This anticancer drug approach merits further development. PMID:26599530

  17. Efficient Negishi coupling reactions of aryl chlorides catalyzed by binuclear and mononuclear nickel-N-heterocyclic carbene complexes.

    Xi, Zhenxing; Zhou, Yongbo; Chen, Wanzhi

    2008-11-01

    We describe the first nickel-N-heterocyclic carbene catalyzed Negishi cross-coupling reaction of a variety of unactivated aryl chlorides, heterocyclic chlorides, aryl dichlorides, and vinyl chloride. The mononuclear and binuclear nickel-NHC complexes supported by heteroarene-functionalized NHC ligands are found to be highly efficient for the coupling of unactivated aryl chlorides and organozinc reagents, leading to biaryls and terphenyls in good to excellent yields under mild conditions. For all aryl chlorides, the binuclear nickel catalysts show activities higher than those of mononuclear nickel complexes because of possible bimetallic cooperative effect. PMID:18841915

  18. New air-stable planar chiral ferrocenyl monophosphine ligands: Suzuki cross-coupling of aryl chlorides and bromides

    Jensen, Jakob Feldthusen; Johannsen, Mogens

    2003-01-01

    GraphicA novel class of planar chiral electron-rich monophosphine ligands has been developed. The modular design allows a short and efficient synthesis of an array of aryl-ferrocenyl derivatives carrying the donating bis(dicyclohexyl)phosphino moiety. These new ligands have successfully been appl...... applied in the palladium-catalyzed Suzuki cross-coupling of activated as well as nonactivated aryl chlorides at room temperature. The asymmetric coupling of an aryl bromide and an aryl boronic acid was also tested, giving ees up to 54%....

  19. Novel Combretastatin-2-aminoimidazole Analogues as Potent Tubulin Assembly Inhibitors: Exploration of Unique Pharmacophoric Impact of Bridging Skeleton and Aryl Moiety.

    Chaudhary, Vikas; Venghateri, Jubina B; Dhaked, Hemendra P S; Bhoyar, Anil S; Guchhait, Sankar K; Panda, Dulal

    2016-04-14

    Combretastatin A-4 (CA-4) in phosphate and serine pro-drug forms is under phase II clinical trials. With our interest of discovering CA-4 inspired new chemical entities, a novel series of 4,5-diaryl-2-aminoimidazole analogues of the compound was designed and synthesized by an efficient and diversity feasible route involving atom economical arene C-H bond arylation. Interestingly, four compounds showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, compound 12 inhibited the proliferation of several types of cancer cells much more efficiently than CA-4. It depolymerized microtubules, induced spindle defects, and stalled mitosis in cells. Compound 12 bound to tubulin and inhibited the polymerization of tubulin in vitro. In addition, podophyllotoxin and CA-4 inhibited the binding of compound 12 to tubulin. The distinctive pharmacophoric features of the bridging motif as well as quinoline nucleus were explored. We noted also a valuable quality of compound 12 as a potential probe in characterizing new CA-4 analogues. PMID:26938120

  20. Synthesis and in vitro antibacterial activity of N-methylnitrone and nitrovinyl derivatives of some N-substituted 2-chloroindol-3-carboxaldehydes

    Gatti, R.; Cavrini, V.; Roveri, P.; Bianucci, F.; Legnani, P.

    1981-02-01

    N-methylnitrones and nitrovinyl derivatives from 1-substituted-2-chloroindol-3-carboxaldehydes were synthesized and evaluated for their in vitro antibacterial activity. Some nitrovinyl derivatives displayed good in vitro activity against Gram-positive bacteria; the compound (II e), 1-(o-chlorobenzyl)-2-chloro-3-(2-nitroethenyl)indole, was more active than nitrofurantoin against Staphylococcus aureus and Streptococcus pyogenes. Some structure-activity relationships are discussed.

  1. Design, synthesis and evaluation of N-aryl-glyoxamide derivatives as structurally novel bacterial quorum sensing inhibitors.

    Nizalapur, Shashidhar; Kimyon, Önder; Biswas, Nripendra Nath; Gardner, Christopher R; Griffith, Renate; Rice, Scott A; Manefield, Mike; Willcox, Mark; Black, David StC; Kumar, Naresh

    2016-01-14

    Bacteria cooperatively regulate the expression of many phenotypes through a mechanism called quorum sensing (QS). Many Gram-negative bacteria use an N-acyl homoserine lactone (AHL)-mediated QS system to control biofilm formation and virulence factor production. In recent years, quorum sensing inhibitors (QSIs) have become attractive tools to overcome antimicrobial resistance exhibited by various pathogenic bacteria. In the present study, we report the design and synthesis of novel N-arylisatin-based glyoxamide derivatives via the ring-opening reaction of N-aryl isatins with cyclic and acylic amines, and amino acid esters. The QSI activity of the synthesized compounds was determined in the LasR-expressing Pseudomonas aeruginosa MH602 and LuxR-expressing Escherichia coli MT102 reporter strains. Compounds 31 and 32 exhibited the greatest QSI activity in P. aeruginosa MH602, with 48.7% and 42.7% reduction in QS activity at 250 μM, respectively, while compounds 31 and 34 showed 73.6% and 43.7% QSI activity in E. coli MT102. In addition, the ability of these compounds to inhibit the production of pyocyanin in P. aeruginosa (PA14) was also determined, with compound 28 showing 47% inhibition at 250 μM. Furthermore, computational docking studies were performed on the LasR receptor protein of P. aeruginosa, which showed that formation of a hydrogen bonding network played a major role in influencing the QS inhibitory activity. We envisage that these novel non-AHL glyoxamide derivatives could become a new tool for the study of QS and potentially for the treatment of bacterial infections. PMID:26552577

  2. Synthesis of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives as potent anti-inflammatory agents and inhibitors of monocyte-to-macrophage transformation.

    Gannarapu, Malla Reddy; Vasamsetti, Sathish Babu; Punna, Nagender; Royya, Naresh Kumar; Pamulaparthy, Shanthan Rao; Nanubolu, Jagadeesh Babu; Kotamraju, Srigiridhar; Banda, Narsaiah

    2014-03-21

    A series of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives 7a-h and 9a-h were synthesized starting from sodium salt of saccharin 1 in series of steps. Final compounds 7a-h and 9a-h were evaluated for the anti-inflammatory activity and their ability to inhibit monocyte-to-macrophage transformation. Compounds 7e, 9b, 9e and 9h showed impressive anti-inflammatory activities (TNF-α, IL-8 and MCP-1) at micro molar concentration which was found to be better than positive control i.e., piroxicam. Compound 9e marginally and compound 9h significantly inhibited PMA-induced MMP-9 gelatinase activity. Also compounds 9e and 9h greatly inhibited the PMA-induced monocyte-to-macrophage transformation, a pre-requisite step in the formation of atheroma. PMID:24531227

  3. Harman induces CYP1A1 enzyme through an aryl hydrocarbon receptor mechanism

    Harman is a common compound in several foods, plants and beverages. Numerous studies have demonstrated its mutagenic, co-mutagenic and carcinogenic effects; however, the exact mechanism has not been fully identified. Aryl hydrocarbon receptor (AhR) is a transcription factor regulating the expression of the carcinogen-activating enzyme; cytochrome P450 1A1 (CYP1A1). In the present study, we examined the ability of harman to induce AhR-mediated signal transduction in human and rat hepatoma cells; HepG2 and H4IIE cells. Our results showed that harman significantly induced CYP1A1 mRNA in a time- and concentration-dependent manner. Similarly, harman significantly induced CYP1A1 at protein and activity levels in a concentration-dependent manner. Moreover, the AhR antagonist, resveratrol, inhibited the increase in CYP1A1 activity by harman. The RNA polymerase inhibitor, actinomycin D, completely abolished the CYP1A1 mRNA induction by harman, indicating a transcriptional activation. The role of AhR in CYP1A1 induction by harman was confirmed by using siRNA specific for human AhR. The ability of harman to induce CYP1A1 was strongly correlated with its ability to stimulate AhR-dependent luciferase activity and electrophoretic mobility shift assay. At post-transcriptional and post-translational levels, harman did not affect the stability of CYP1A1 at the mRNA and the protein levels, excluding other mechanisms participating in the obtained effects. We concluded that harman can directly induce CYP1A1 gene expression in an AhR-dependent manner and may represent a novel mechanism by which harman promotes mutagenicity, co-mutagenicity and carcinogenicity.

  4. Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer

    Brokken, Leon J. S.; Lundberg-Giwercman, Yvonne; Meyts, Ewa Rajpert-De; Eberhard, Jakob; Ståhl, Olof; Cohn-Cedermark, Gabriella; Daugaard, Gedske; Arver, Stefan; Giwercman, Aleksander

    2013-01-01

    In the Western world, testicular germ cell cancer (TGCC) is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing incidence of TGCC in some countries. Additionally, there is a strong genetic component that affects susceptibility. However, genetic polymorphisms that have been identified so far only partially explain the risk of TGCC. Many of the persistent environmental pollutants act through the aryl hydrocarbon receptor (AHR). AHR signaling pathway is known to interfere with reproductive hormone signaling, which is supposed to play a role in the pathogenesis and invasive progression of TGCC. The aim of the present study was to identify whether AHR-related polymorphisms were associated with risk as well as histological and clinical features of TGCC in 367 patients and 537 controls. Haplotype-tagging single-nucleotide polymorphisms (SNPs) were genotyped in genes encoding AHR and AHR repressor (AHRR). Binary logistic regression was used to calculate the risk of TGCC, non-seminoma versus seminoma, and metastasis versus localized disease. Four SNPs in AHRR demonstrated a significant allele association with risk to develop metastases (rs2466287: OR = 0.43, 95% CI 0.21–0.90; rs2672725: OR = 0.49, 95% CI: 0.25–0.94; rs6879758: OR = 0.27, 95% CI: 0.08–0.92; rs6896163: OR = 0.34, 95% CI: 0.12–0.98). This finding supports the hypothesis that compounds acting through AHR may play a role in the invasive progression of TGCC, either directly or through modification of reproductive hormone action. PMID:23420531

  5. Toxicological implications of polymorphisms in receptors for xenobiotic chemicals: The case of the aryl hydrocarbon receptor

    Mechanistic toxicology has predominantly been focused on adverse effects that are caused by reactive metabolites or by reactive oxygen species. However, many important xenobiotics exert their toxicity, not by generating reactive products, but rather by altering expression of specific genes. In particular, some environmental contaminants target nuclear receptors that function as regulators of transcription. For example, binding of xenobiotic chemicals to steroid receptors is a principle mechanism of endocrine disruption. The aryl hydrocarbon receptor (AHR) mediates toxicity of dioxin-like compounds. In mice, a polymorphism in the AHR ligand-binding domain reduces binding affinity by about 10-fold in the DBA/2 strain compared with the C57BL/6 strain; consequently, dose-response curves for numerous biochemical and toxic effects are shifted about one log to the right in DBA/2 mice. In the Han/Wistar (Kuopio) (H/W) rat strain, a polymorphism causes a deletion of 38 or 43 amino acids from the AHR transactivation domain. This deletion is associated with a greater than 1000-fold resistance to lethality from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Genes in the conventional AH gene battery (e.g. CYP1A1, CYP1A2, CYP1B1, ALDH3A1, NQO1 and UGT1A1) remain responsive to TCDD in H/W rats despite the large deletion. However, the deletion may selectively alter the receptor's ability to dysregulate specific genes that are key to dioxin toxicity. We are identifying these genes using an expression array approach in dioxin-sensitive vs. dioxin-resistant rat strains and lines. Polymorphisms exist in the human AH receptor, but thus far they have not been shown to have any substantial effect on human responses to AHR-ligands

  6. What Are the Potential Sites of Protein Arylation by N-Acetyl-p-benzoquinone Imine (NAPQI)?

    Leeming, Michael G; Gamon, Luke F; Wille, Uta; Donald, William A; O'Hair, Richard A J

    2015-11-16

    Acetaminophen (paracetamol, APAP) is a safe and widely used analgesic medication when taken at therapeutic doses. However, APAP can cause potentially fatal hepatotoxicity when taken in overdose or in patients with metabolic irregularities. The production of the electrophilic and putatively toxic compound N-acetyl-p-benzoquinone imine (NAPQI), which cannot be efficiently detoxicated at high doses, is implicated in APAP toxicity. Numerous studies have identified that excess NAPQI can form covalent linkages to the thiol side chains of cysteine residues in proteins; however, the reactivity of NAPQI toward other amino acid side chains is largely unexplored. Here, we report a survey of the reactivity of NAPQI toward 11 N-acetyl amino acid methyl esters and four peptides. (1)H NMR analysis reveals that NAPQI forms covalent bonds to the side-chain functional groups of cysteine, methionine, tyrosine, and tryptophan residues. Analogous reaction products were observed when NAPQI was reacted with synthetic model peptides GAIL-X-GAILR for X = Cys, Met, Tyr, and Trp. Tandem mass spectrometry peptide sequencing showed that the NAPQI modification sites are located on the "X" residue in each case. However, when APAP and the GAIL-X-GAILR peptide were incubated with rat liver microsomes that contain many metabolic enzymes, NAPQI formed by oxidative metabolism reacted with GAIL-C-GAILR exclusively. For the peptides where X = Met, Tyr, and Trp, competing reactions between NAPQI and alternative nucleophiles precluded arylation of the target peptide by NAPQI. Although Cys residues are favorably targeted under these conditions, these data suggest that NAPQI can, in principle, also damage proteins at Met, Tyr, and Trp residues. PMID:26523953

  7. The aryl hydrocarbon receptor promotes aging phenotypes across species.

    Eckers, Anna; Jakob, Sascha; Heiss, Christian; Haarmann-Stemmann, Thomas; Goy, Christine; Brinkmann, Vanessa; Cortese-Krott, Miriam M; Sansone, Roberto; Esser, Charlotte; Ale-Agha, Niloofar; Altschmied, Joachim; Ventura, Natascia; Haendeler, Judith

    2016-01-01

    The ubiquitously expressed aryl hydrocarbon receptor (AhR) induces drug metabolizing enzymes as well as regulators of cell growth, differentiation and apoptosis. Certain AhR ligands promote atherosclerosis, an age-associated vascular disease. Therefore, we investigated the role of AhR in vascular functionality and aging. We report a lower pulse wave velocity in young and old AhR-deficient mice, indicative of enhanced vessel elasticity. Moreover, endothelial nitric oxide synthase (eNOS) showed increased activity in the aortas of these animals, which was reflected in increased NO production. Ex vivo, AhR activation reduced the migratory capacity of primary human endothelial cells. AhR overexpression as well as treatment with a receptor ligand, impaired eNOS activation and reduced S-NO content. All three are signs of endothelial dysfunction. Furthermore, AhR expression in blood cells of healthy human volunteers positively correlated with vessel stiffness. In the aging model Caenorhabditis elegans, AhR-deficiency resulted in increased mean life span, motility, pharynx pumping and heat shock resistance, suggesting healthier aging. Thus, AhR seems to have a negative impact on vascular and organismal aging. Finally, our data from human subjects suggest that AhR expression levels could serve as an additional, new predictor of vessel aging. PMID:26790370

  8. Evodiamine as a novel antagonist of aryl hydrocarbon receptor

    Yu, Hui [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Department of Laboratory Medicine, The Affiliated Tenth People' s Hospital, Tongji University, Shanghai 200072 (China); Tu, Yongjiu; Zhang, Chun; Fan, Xia; Wang, Xi [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Wang, Zhanli [College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014 (China); Liang, Huaping, E-mail: huaping_liang@yahoo.com.cn [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China)

    2010-11-05

    Research highlights: {yields} Evodiamine interacted with the AhR. {yields} Evodiamine inhibited the specific binding of [{sup 3}H]-TCDD to the AhR. {yields} Evodiamine acts as an antagonist of the AhR. -- Abstract: Evodiamine, the major bioactive alkaloid isolated from Wu-Chu-Yu, has been shown to interact with a wide variety of proteins and modify their expression and activities. In this study, we investigated the interaction between evodiamine and the aryl hydrocarbon receptor (AhR). Molecular modeling results revealed that evodiamine directly interacted with the AhR. Cytosolic receptor binding assay also provided the evidence that evodiamine could interact with the AhR with the K{sub i} value of 28.4 {+-} 4.9 nM. In addition, we observed that evodiamine suppressed the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nuclear translocation of the AhR and the expression of CYP1A1 dose-dependently. These results suggested that evodiamine was able to bind to the AhR as ligand and exhibit antagonistic effects.

  9. Aryl hydrocarbon receptor control of a disease tolerance defence pathway.

    Bessede, Alban; Gargaro, Marco; Pallotta, Maria T; Matino, Davide; Servillo, Giuseppe; Brunacci, Cinzia; Bicciato, Silvio; Mazza, Emilia M C; Macchiarulo, Antonio; Vacca, Carmine; Iannitti, Rossana; Tissi, Luciana; Volpi, Claudia; Belladonna, Maria L; Orabona, Ciriana; Bianchi, Roberta; Lanz, Tobias V; Platten, Michael; Della Fazia, Maria A; Piobbico, Danilo; Zelante, Teresa; Funakoshi, Hiroshi; Nakamura, Toshikazu; Gilot, David; Denison, Michael S; Guillemin, Gilles J; DuHadaway, James B; Prendergast, George C; Metz, Richard; Geffard, Michel; Boon, Louis; Pirro, Matteo; Iorio, Alfonso; Veyret, Bernard; Romani, Luigina; Grohmann, Ursula; Fallarino, Francesca; Puccetti, Paolo

    2014-07-10

    Disease tolerance is the ability of the host to reduce the effect of infection on host fitness. Analysis of disease tolerance pathways could provide new approaches for treating infections and other inflammatory diseases. Typically, an initial exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness to further LPS challenge (endotoxin tolerance). We found that a first exposure of mice to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase, which provided an activating ligand to the former, to downregulate early inflammatory gene expression. However, on LPS rechallenge, AhR engaged in long-term regulation of systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1 (IDO1). AhR-complex-associated Src kinase activity promoted IDO1 phosphorylation and signalling ability. The resulting endotoxin-tolerant state was found to protect mice against immunopathology in Gram-negative and Gram-positive infections, pointing to a role for AhR in contributing to host fitness. PMID:24930766

  10. Aryl hydrocarbon receptor control of a disease tolerance defense pathway

    Bessede, Alban; Gargaro, Marco; Pallotta, Maria T; Matino, Davide; Servillo, Giuseppe; Brunacci, Cinzia; Bicciato, Silvio; Mazza, Emilia MC; Macchiarulo, Antonio; Vacca, Carmine; Iannitti, Rossana; Tissi, Luciana; Volpi, Claudia; Belladonna, Maria L; Orabona, Ciriana; Bianchi, Roberta; Lanz, Tobias; Platten, Michael; Fazia, Maria A Della; Piobbico, Danilo; Zelante, Teresa; Funakoshi, Hiroshi; Nakamura, Toshikazu; Gilot, David; Denison, Michael S; Guillemin, Gilles J; DuHadaway, James B; Prendergast, George C; Metz, Richard; Geffard, Michel; Boon, Louis; Pirro, Matteo; Iorio, Alfonso; Veyret, Bernard; Romani, Luigina; Grohmann, Ursula; Fallarino, Francesca; Puccetti, Paolo

    2014-01-01

    Summary Disease tolerance is the ability of the host to reduce the impact of infection on host fitness. Analysis of disease tolerance pathways could provide new approaches for treating infections and other inflammatory diseases. Typically, an initial exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness to further LPS challenge (“endotoxin tolerance”). We found that a first exposure to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase 2, which provided an activating ligand to the former, to downregulate early inflammatory gene expression. However, on LPS rechallenge, AhR engaged in long-term regulation of systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1 (IDO1). AhR complex-associated Src kinase activity promoted IDO1 phosphorylation and signaling ability. The resulting endotoxin-tolerant state was found to protect mice against immunopathology in gram-negative and gram-positive infections, pointing to a role for AhR in contributing to host fitness. PMID:24930766

  11. Structure-based design of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoates as selective inhibitors of the Mcl-1 oncoprotein.

    Lanning, Maryanna E; Yu, Wenbo; Yap, Jeremy L; Chauhan, Jay; Chen, Lijia; Whiting, Ellis; Pidugu, Lakshmi S; Atkinson, Tyler; Bailey, Hala; Li, Willy; Roth, Braden M; Hynicka, Lauren; Chesko, Kirsty; Toth, Eric A; Shapiro, Paul; MacKerell, Alexander D; Wilder, Paul T; Fletcher, Steven

    2016-05-01

    Structure-based drug design was utilized to develop novel, 1-hydroxy-2-naphthoate-based small-molecule inhibitors of Mcl-1. Ligand design was driven by exploiting a salt bridge with R263 and interactions with the p2 pocket of the protein. Significantly, target molecules were accessed in just two synthetic steps, suggesting further optimization will require minimal synthetic effort. Molecular modeling using the Site-Identification by Ligand Competitive Saturation (SILCS) approach was used to qualitatively direct ligand design as well as develop quantitative models for inhibitor binding affinity to Mcl-1 and the Bcl-2 relative Bcl-xL as well as for the specificity of binding to the two proteins. Results indicated hydrophobic interactions in the p2 pocket dominated affinity of the most favourable binding ligand (3bl: Ki = 31 nM). Compounds were up to 19-fold selective for Mcl-1 over Bcl-xL. Selectivity of the inhibitors was driven by interactions with the deeper p2 pocket in Mcl-1 versus Bcl-xL. The SILCS-based SAR of the present compounds represents the foundation for the development of Mcl-1 specific inhibitors with the potential to treat a wide range of solid tumours and hematological cancers, including acute myeloid leukemia. PMID:26985630

  12. In vitro cytotoxicity and apoptotic inducing activity of the synthesized 4-aryl-4H-chromenes derivatives against human cancer cell lines

    Mohagheghi MA

    2009-09-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: 4-Aryl-4H-chromenes are novel anticancer agents which induce apoptosis in cancer cells. These compounds were found to induce apoptosis by targeting the tubulin/microtubule system in cell proliferation process. The aim of this study was to report cyototoxic and apoptosis inducing activities of a new series of synthesized 4-aryl-4H-chromenes compounds."n"n Methods: The in vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated against a paned of human cancer cell lines including MCF-7 (breast carcinoma, A549 (lung carcinoma, HEPG-2 (liver carcinoma, SW-480 (colon adenocarcinoma, U87-MG (glioblastoma, 1321N1 (astrocytoma, and DAOY (medulloblastoma. The percentage of growth inhibitory activity was evaluated using MTT colorimetric assay versus controls not treated with test derivatives. The data for etoposide, a well known anticancer drug, was included for comparison. For each compound, the 50% inhibitory concentration (IC50 were determined. Apoptosis inducing activity were assessed by DAPI staining."n"n Results: Preliminary screening showed that those chromenes analogs bearing phenyl-isoxazole-3-yl substitution or the derivatives containing methoxyphenyl in chromene ring exhibited cytotoxic and apoptotic inducing activity comparable with or even superior than the reference drug, etoposide. The compounds without this type of substitution have lower activity. "n"nConclusions: Replacement of 3, 4, 5-trimethoxyphenyl group with thiazol ring in the synthesized derivatives reduced the cytotoxic activity. However, the derivatives with phenyl-isoxazole analogue showed potent cytotoxic and apoptotic inducing activity.

  13. Enhanced interfacial properties of carbon fiber composites via aryl diazonium reaction on water

    Wang, Yuwei [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China); College of Materials Science and Engineering, Qiqihar University, Qiqihar 161006 (China); Meng, Linghui [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China); Fan, Liquan [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China); College of Materials Science and Engineering, Qiqihar University, Qiqihar 161006 (China); Ma, Lichun; Qi, Meiwei; Yu, Jiali [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China); Huang, Yudong, E-mail: ydhuang.hit1@yahoo.com.cn [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China)

    2014-10-15

    Highlights: Carbon fibers are grafted with phenyl amine group via aryl diazonium reaction. Interfacial shear strength of the carbon fibers increases by 73%. Tensile strength of the carbon fibers does not decrease distinctly. Using water as the reaction medium can avoid pollution from organic solvents. Grafting via aryl diazonium reaction in one step can improve modification efficiency. - Abstract: Polyacrylonitrile-based carbon fibers were functionalized with phenyl amine group via aryl diazonium reaction on water to improve their interfacial bonding with resin matrix. Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy were employed to characterize ordered degree, functional groups, chemical states and morphology of carbon fiber surface, respectively. The results showed that phenyl amine groups were grafted on the fiber surface successfully. Mechanical property test results indicated that the aryl diazonium reaction in this paper could improve the interfacial shear strength by 73%, while the tensile strength was down very slightly. Hence aryl diazonium reaction on water could be a facile green platform to functionalize carbon fibers for many interesting applications.

  14. Enhanced interfacial properties of carbon fiber composites via aryl diazonium reaction on water

    Highlights: Carbon fibers are grafted with phenyl amine group via aryl diazonium reaction. Interfacial shear strength of the carbon fibers increases by 73%. Tensile strength of the carbon fibers does not decrease distinctly. Using water as the reaction medium can avoid pollution from organic solvents. Grafting via aryl diazonium reaction in one step can improve modification efficiency. - Abstract: Polyacrylonitrile-based carbon fibers were functionalized with phenyl amine group via aryl diazonium reaction on water to improve their interfacial bonding with resin matrix. Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy were employed to characterize ordered degree, functional groups, chemical states and morphology of carbon fiber surface, respectively. The results showed that phenyl amine groups were grafted on the fiber surface successfully. Mechanical property test results indicated that the aryl diazonium reaction in this paper could improve the interfacial shear strength by 73%, while the tensile strength was down very slightly. Hence aryl diazonium reaction on water could be a facile green platform to functionalize carbon fibers for many interesting applications

  15. Expedient synthesis of C-aryl carbohydrates by consecutive biocatalytic benzoin and aldol reactions.

    Hernández, Karel; Parella, Teodor; Joglar, Jesús; Bujons, Jordi; Pohl, Martina; Clapés, Pere

    2015-02-16

    The introduction of aromatic residues connected by a C-C bond into the non-reducing end of carbohydrates is highly significant for the development of innovative structures with improved binding affinity and selectivity (e.g., C-aril-sLex). In this work, an expedient asymmetric "de novo" synthetic route to new aryl carbohydrate derivatives based on two sequential stereoselectively biocatalytic carboligation reactions is presented. First, the benzoin reaction of aromatic aldehydes to dimethoxyacetaldehyde is conducted, catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I. Then, the α-hydroxyketones formed are reduced by using NaBH4 yielding the anti diol. After acetal hydrolysis, the aldol addition of dihydroxyacetone, hydroxyacetone, or glycolaldehyde catalyzed by the stereocomplementary D-fructose-6-phosphate aldolase and L-rhamnulose-1-phosphate aldolase is performed. Both aldolases accept unphosphorylated donor substrates, avoiding the need of handling the phosphate group that the dihydroxyacetone phosphate-dependent aldolases require. In this way, 6-C-aryl-L-sorbose, 6-C-aryl-L-fructose, 6-C-aryl-L-tagatose, and 5-C-aryl-L-xylose derivatives are prepared by using this methodology. PMID:25640727

  16. Aryl sulfate formation in sea urchins (Strongylocentrotus droebachiensis) ingesting marine algae (Fucus distichus) containing 2,6-dimethylnapthalene

    The metabolism of tritiated 2,6-dimethylnapthalene (2,6-DMN) was studied in sea urchins (Strongylocentrotus droebachiensis) feeding on marine algae (Fucus distichus). The Fucus accumulated this hydrocarbon from sea water without converting it to metabolites. Most of the tritium accumulated by the sea urchins (e.g., 70.8% after 3 days) from feeding on 2,6-DMN-exposed Fucus was present in the exoskeleton (shell and spines). Moreover, after 3 days feeding, about 90% of the tritium in the total metabolite fraction of the gonads and digestive tract of the sea urchin was present as sulfate derivatives. These metabolites were identified through hydrolysis with aryl sulfatase, followed by thin-layer chromatography of the products. After 14 days of feeding, the tritium associated with the sulfate derivatives decreased in the gonads and digestive tract to 61 and 65%, respectively, of the total metabolite fraction. Hydroxy compounds from sulfatase hydrolysis were chromatographed using multiple elutions with toluene. The hydroxy isomers were separated and the R/sub f/ values were compared to those of pure reference compounds. The data indicated that 80% of the 2,6-dimethylnaphtyl sulfate contained the sulfate on the 1 and/or 3 position of the aromatic ring. Moreover, 6-methyl-2-naphthalenemethanol was not detected, which implies that sea urchins, unlike fish, metabolize alkyl-substituted aromatic hydrocarbons primarily through aromatic ring oxidations

  17. (E)-4-aryl-4-oxo-2-butenoic acid amides, chalcone–aroylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization

    Vitorović-Todorović, Maja D.; Erić-Nikolić, Aleksandra; Kolundžija, Branka; Hamel, Ernest; Ristić, Slavica; Juranić, Ivan O.; Drakulić, Branko J.

    2013-01-01

    Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity in one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed tubulin assembly inhibition at concentrations <20 μM. The most potent inhibitor of tubulin assembly was unsubstituted compound 1, with IC50 = 2.9 μM. Compound 23 had an oral LD50 in vivo of 45 mg/kg in mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin agents. PMID:23353745

  18. In vitro evaluation of anti-pathogenic surface coating nanofluid, obtained by combining Fe3O4/C12 nanostructures and 2-((4-ethylphenoxy)methyl)- N-(substituted-phenylcarbamothioyl)-benzamides

    Anghel, Ion; Limban, Carmen; Grumezescu, Alexandru Mihai; Anghel, Alina Georgiana; Bleotu, Coralia; Chifiriuc, Mariana Carmen

    2012-09-01

    In this paper, we report the design of a new nanofluid for anti-pathogenic surface coating. For this purpose, new 2-((4-ethylphenoxy)methyl)- N-(substituted-phenylcarbamothioyl)-benzamides were synthesized and used as an adsorption shell for Fe3O4/C12 core/shell nanosized material. The functionalized specimens were tested by in vitro assays for their anti-biofilm properties and biocompatibility. The optimized catheter sections showed an improved resistance to Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 in vitro biofilm development, as demonstrated by the viable cell counts of biofilm-embedded bacterial cells and by scanning electron microscopy examination of the colonized surfaces. The nanofluid proved to be not cytotoxic and did not influence the eukaryotic cell cycle. These results could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with improved anti-biofilm properties.

  19. Synthesis and evaluation of 2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)-N-(3-(trifluoromethyl)phenyl)acetamides and N-(4-chloro-3-fluorophenyl)-2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)acetamides as antimicrobial agents

    Kalpesh Parikh; Deepkumar Joshi

    2014-05-01

    A series of 2-mercapto-5-phenyl-1,3,4-oxadiazole derivatives have been condensed with different phenyl acetamide derivatives possessing fluorine atom at meta position; resulting in the formation of 2-(5-aryl- 1,3,4-oxadiazol-2-ylthio)-N-(3-(trifluoromethyl)phenyl)acetamide (5a-j) and N-(4-chloro-3-fluorophenyl)-2-(5-aryl-1,3,4-oxadiazol-2-ylthio)acetamide (5k-t) derivatives. The antimicrobial properties of the synthesized entities (5a-t) measured as their MIC (Minimum Inhibitory Concentration) values were evaluated by using the broth dilution method against Gram-positive bacteria (S. aureus and E. faecalis), Gram-negative bacteria (E. coli and P. aeruginosa) and fungi (C. albicans and A. niger). The results of antimicrobial activities (in g/ml) revealed the fact that the compounds 5a and g bearing a maximum number of fluorine atoms showed the highest potency among the synthesized compounds against the broad panel of bacterial and fungal strains. The presence of fluorine atom at the meta position in the phenyl ring of final derivatives (5a-t) brought about an enhancement of their antimicrobial properties to a notable extent.

  20. Nickel-catalyzed Kumada cross-coupling reactions of tertiary alkylmagnesium halides and aryl bromides/triflates.

    Joshi-Pangu, Amruta; Wang, Chao-Yuan; Biscoe, Mark R

    2011-06-01

    We report a Ni-catalyzed process for the cross-coupling of tertiary alkyl nucleophiles and aryl bromides. This process is extremely general for a wide range of electrophiles and generally occurs with a ratio of retention to isomerization >30:1. The same procedure also accommodates the use of aryl triflates, vinyl chlorides, and vinyl bromides as the electrophilic component. PMID:21553878

  1. A Convenient Palladium-Catalyzed Carbonylative Suzuki Coupling of Aryl Halides with Formic Acid as the Carbon Monoxide Source.

    Qi, Xinxin; Jiang, Li-Bing; Li, Hao-Peng; Wu, Xiao-Feng

    2015-12-01

    A practical palladium-catalyzed carbonylative Suzuki coupling of aryl halides under carbon monoxide gas-free conditions has been developed. Here, formic acid was utilized as the carbon monoxide source for the first time with acetic anhydride as the additive. A variety of diarylketones were produced in moderate to excellent yields from the corresponding aryl halides and arylboronic acids. PMID:26486227

  2. A practical cobalt-catalyzed cross-coupling of benzylic zinc reagents with aryl and heteroaryl bromides or chlorides.

    Benischke, Andreas D; Knoll, Irina; Rérat, Alice; Gosmini, Corinne; Knochel, Paul

    2016-02-11

    A catalytic system consisting of 5 mol% CoCl2 and 10 mol% isoquinoline allows a convenient cross-coupling of benzylic zinc reagents with various aryl and heteroaryl bromides or chlorides leading to polyfunctionalized diaryl- and aryl-heteroaryl-methane derivatives. PMID:26806016

  3. Dithiocarbamate promoted practical synthesis of N-Aryl-2-aminobenzazoles: Synthesis of novel Aurora-A kinase inhibitor

    Naresh Kumar Katari; M Venkatanarayana; Kummari Srinivas

    2015-03-01

    Various N-aryl-2-aminobenzoxazoles and N-aryl-2-aminobenzothiazoles were synthesized from o-aminophenol and o-aminothiophenol, respectively, mediated by dithiocarbamate in one step. The salient features of this method include mild reaction condition, high yield and large scale synthesis. Application of this methodology has been demonstrated by synthesizing potent Aurora kinase-A inhibitors.

  4. Aryne generation vs. Truce-Smiles and fries rearrangements during the Kobayashi fragmentation reaction: a new bi-aryl synthesis.

    Rasheed, O K; Hardcastle, I R; Raftery, J; Quayle, P

    2015-08-01

    Treatment of (ortho-trimethysilyl)aryl phenylsulfonates with a soluble fluoride source initiates a Truce-Smiles rearrangement leading to the formation of functionalized bi-aryls. This new carbon-carbon bond-forming reaction proceeds without recourse to transition metal catalysis, under mild reaction conditions and with good functional group compatibility. PMID:26126413

  5. Copper-Catalyzed N-Arylation of Amides Using (S-N-Methylpyrrolidine-2-carboxylate as the Ligand

    Dong-Sheng Ma

    2010-03-01

    Full Text Available (S-N-methylpyrrolidine-2-carboxylate, a derivative of natural L-proline, was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides with aryl halides under mild conditions. A variety of N-arylamides were synthesized in good to high yields.

  6. Homocoupling of aryl halides in flow: Space integration of lithiation and FeCl3 promoted homocoupling

    Aiichiro Nagaki

    2011-08-01

    Full Text Available The use of FeCl3 resulted in a fast homocoupling of aryllithiums, and this enabled its integration with the halogen–lithium exchange reaction of aryl halides in a flow microreactor. This system allows the homocoupling of two aryl halides bearing electrophilic functional groups, such as CN and NO2, in under a minute.

  7. A General Palladium-Catalyzed Hiyama Cross-Coupling Reaction of Aryl and Heteroaryl Chlorides.

    Yuen, On Ying; So, Chau Ming; Man, Ho Wing; Kwong, Fuk Yee

    2016-05-01

    A general palladium-catalyzed Hiyama cross-coupling reaction of aryl and heteroaryl chlorides with aryl and heteroaryl trialkoxysilanes by a Pd(OAc)2 /L2 catalytic system is presented. A newly developed water addition protocol can dramatically improve the product yields. The conjugation of the Pd/L2 system and the water addition protocol can efficiently catalyze a broad range of electron-rich, -neutral, -deficient, and sterically hindered aryl chlorides and heteroaryl chlorides with excellent yields within three hours and the catalyst loading can be down to 0.05 mol % Pd for the first time. Hiyama coupling of heteroaryl chlorides with heteroaryl silanes is also reported for the first time. The reaction can be easily scaled up 200 times (100 mmol) without any degasification and purification of reactants; this facilitates the practical application in routine synthesis. PMID:26998586

  8. Intramolecular Direct Arylation of 3-Halo-2-pyrones and 2-Coumarins.

    Nolan, Marie-T; Pardo, Leticia M; Prendergast, Aisling M; McGlacken, Gerard P

    2015-11-01

    Direct arylation represents a favorable alternative to traditional cross-coupling and has found widespread use with simple aryls and robust heterocycles. Herein a direct arylation protocol has been optimized and applied to 2-pyrones, which are delicate and privileged biological motifs. Regioselective halogenation at the 3-position allows intramolecular coupling by activation of a pyrone C-Br or C-Cl bond and a phenoxy C-H bond. Importantly, electron-poor phenoxy substrates also worked well. The methodology was extended to 2-coumarins and applied to the synthesis of flemichapparin C and a novel analogue. Deuterium isotope effects, typical of a concerted metalation-deprotonation (CMD) mechanism, were observed in the case of a bromopyrone, but a highly unusual, inverse kinetic isotope effect was evident using a chlorocoumarin, implying that a different mechanism is operating. PMID:26491882

  9. N-aryl pyrrolo-tetrathiafulvalene based ligands: synthesis and metal coordination.

    Balandier, Jean-Yves; Chas, Marcos; Dron, Paul I; Goeb, Sébastien; Canevet, David; Belyasmine, Ahmed; Allain, Magali; Sallé, Marc

    2010-03-01

    A straightforward general synthetic access to N-aryl-1,3-dithiolo[4,5-c]pyrrole-2-thione derivatives 6 from acetylenedicarbaldehyde monoacetal is depicted. In addition to their potentiality as precursors to dithioalkyl-pyrrole derivatives, thiones 6 are key building blocks to N-aryl monopyrrolo-tetrathiafulvalene (MPTTF) derivatives 10. X-ray structures of four of these thiones intermediates, reminiscent of the corresponding MPTTF derivatives, are provided. When the aryl group is a binding pyridyl unit, the MPTTF derivative 10a can coordinate M(II) salts (M = Pt, Pd). The first examples of metal-directed orthogonal MPTTF-based dimers 11-14, obtained through coordination of 10a to cis-blocked square planar Pt or Pd complexes are described. Studies on the parameters influencing the dimer construction are presented, as well as first recognition properties of the resulting electron-rich clip for C(60). PMID:20143799

  10. Regioselective Multi-component Synthesis of 7-Aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-diones Catalyzed by n-Propylsulfonated ?-Al2O3

    We have developed a straightforward method for the synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b] quinazoline-5,6-dione derivatives by nano n-propylsulfonated ?-Al2O3 catalyzed three-component reaction of aldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino-1,2,4-triazole. A series of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-dione derivatives have been synthesized in excellent yield (85-96%). The catalyst can be recycled up to six cycles without much decrease in catalytic activity. Environment friendly catalyst, high regioselectivity and good yield are the advantages of the method. To the best of our knowledge this is the first report on synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-dione derivatives. We are evaluating anticancer activity of 4, which will be published elsewhere. Naphthoquinones constitute a major class of naturally occurring compounds, and interests in their chemistry continues unabated because of their wide range of biological and therapeutic properties such as antioxidant, antifungal, anti-inflammatory, antiallergic, antiviral, and anticancer activity

  11. Regioselective Multi-component Synthesis of 7-Aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-diones Catalyzed by n-Propylsulfonated ?-Al{sub 2}O{sub 3}

    Li, Weilin; Tian, Shuanbao; Wu, Liqiang [Xinxiang Medical Univ., Xinxiang (China)

    2013-09-15

    We have developed a straightforward method for the synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b] quinazoline-5,6-dione derivatives by nano n-propylsulfonated ?-Al{sub 2}O{sub 3} catalyzed three-component reaction of aldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino-1,2,4-triazole. A series of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-dione derivatives have been synthesized in excellent yield (85-96%). The catalyst can be recycled up to six cycles without much decrease in catalytic activity. Environment friendly catalyst, high regioselectivity and good yield are the advantages of the method. To the best of our knowledge this is the first report on synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-dione derivatives. We are evaluating anticancer activity of 4, which will be published elsewhere. Naphthoquinones constitute a major class of naturally occurring compounds, and interests in their chemistry continues unabated because of their wide range of biological and therapeutic properties such as antioxidant, antifungal, anti-inflammatory, antiallergic, antiviral, and anticancer activity.

  12. Unsymmetrical Aryl(2,4,6-trimethoxyphenyl)iodonium Salts: One-Pot Synthesis, Scope, Stability, and Synthetic Studies.

    Seidl, Thomas L; Sundalam, Sunil K; McCullough, Brennen; Stuart, David R

    2016-03-01

    Diaryliodonium salts have recently attracted significant attention as metal-free-arylation reagents in organic synthesis, and efficient access to these salts is critical for advancement of their use in reaction discovery and development. The trimethoxybenzene-derived auxiliary is a promising component of unsymmetrical variants, yet access remains limited. Here, a one-pot synthesis of aryl(2,4,6-trimethoxyphenyl)iodonium salts from aryl iodides, m-CPBA, p-toluenesulfonic acid, and trimethoxybenzene is described. Optimization of the reaction conditions for this one-pot synthesis was enabled by the method of multivariate analysis. The reaction is fast (85% average), and has broad substrate scope (>25 examples) including elaborate aryl iodides. The utility of these reagents is demonstrated in moderate to high yielding arylation reactions with C-, N-, O-, and S-nucleophiles including the synthesis of a liquid crystal molecule. PMID:26828570

  13. Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

    Akahoshi Eiichi

    2009-06-01

    Full Text Available Abstract Background Dioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (AhR. This study focused on the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD exposure on the regulation of TH, a rate-limiting enzyme of dopamine synthesis, gene expression by AhR. Methods N2a-Rβ cells were established by transfecting murine neuroblastoma Neuro2a with the rat AhR cDNA. TH expression induced by TCDD was assessed by RT-PCR and Western blotting. Participation of AhR in TCDD-induced TH gene expression was confirmed by suppressing AhR expression using the siRNA method. Catecholamines including dopamine were measured by high-performance liquid chromatography. A reporter gene assay was used to identify regulatory motifs in the promoter region of TH gene. Binding of AhR with the regulatory motif was confirmed by an electrophoretic mobility shift assay (EMSA. Results Induction of TH by TCDD through AhR activation was detected at mRNA and protein levels. Induced TH protein was functional and its expression increased dopamine synthesis. The reporter gene assay and EMSA indicated that AhR directly regulated TH gene expression. Regulatory sequence called aryl hydrocarbon receptor responsive element III (AHRE-III was identified upstream of the TH gene from -285 bp to -167 bp. Under TCDD exposure, an AhR complex was bound to AHRE-III as well as the xenobiotic response element (XRE, though AHRE-III was not identical to XRE, the conventional AhR-binding motif. Conclusion Our results suggest TCDD directly regulate the dopamine system by TH gene transactivation via an AhR-AHRE-III-mediated pathway. The AhR- mediated pathway could have a particular AhR-mediated genomic control pathway transmitting the effects of TCDD action to target cells in the development of dopaminergic disabilities.

  14. Replacing Conventional Carbon Nucleophiles with Electrophiles: Nickel-Catalyzed Reductive Alkylation of Aryl Bromides and Chlorides

    Everson, Daniel A.; Jones, Brittany A.; Weix, Daniel J.

    2012-01-01

    A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (−OH, −NHTs, −OAc, −OTs, −OTf, −COMe, −NHBoc, −NHCbz, −CN, −SO2Me), and the reactions are assem...

  15. A Metal-Free Synthesis of N-Aryl Carbamates under Ambient Conditions.

    Guo, Wusheng; Gnzalez-Fabra, Joan; Bandeira, Nuno A G; Bo, Carles; Kleij, Arjan W

    2015-09-28

    The first chemo- and site-selective process for the formation of N-aryl-carbamates from cyclic organic carbonates and aromatic amines is reported. The reactions proceed smoothly under extremely mild reaction conditions using TBD (triazabicyclodecene) as an effective and cheap organocatalyst, thus providing a sustainable and new methodology for the formation of a wide variety of useful N-aryl carbamate synthons in good to excellent yields. Computational investigations have been performed and show the underlying reason for the observed unique reactivity as related to an effective proton-relay mechanism mediated by the bicyclic guanidine base. PMID:26385130

  16. Kinetic and chemical characterization of aldehyde oxidation by fungal aryl-alcohol oxidase

    Ferreira, Patricia; Hernández-Ortega, Aitor; Herguedas, Beatriz; Rencoret, Jorge; Gutiérrez, Ana; Martínez, Maria Jesús; Jiménez-Barbero, Jesús; Medina, Milagros; Martínez, Ángel T.

    2010-01-01

    Abstract Fungal aryl-alcohol oxidase (AAO) provides H2O2 for lignin biodegradation. AAO is active on benzyl alcohols that are oxidized to aldehydes. However, the H2O2 formed from some of them was more than stoichiometric with respect to the aldehyde detected. This was due to a double reaction that involves aryl-aldehyde oxidase activity. The latter was investigated using different benzylic aldehydes, whose oxidation to acids was demonstrated by GC-MS. The steady and pre-steady stat...

  17. Organocatalytic asymmetric arylative dearomatization of 2,3-disubstituted indoles enabled by tandem reactions.

    Zhang, Yu-Chen; Zhao, Jia-Jia; Jiang, Fei; Sun, Si-Bing; Shi, Feng

    2014-12-01

    The organocatalytic asymmetric arylative dearomatization of indoles was achieved through two tandem approaches involving 2,3-disubstituted indoles and quinone imine ketals. One approach utilized the enantioselective cascade 1,4 addition/alcohol elimination reaction, the other employed the one-pot tandem arylative dearomatization/transfer hydrogenation sequence. In both cases, enantiomerically pure indole derivatives that bear an all-carbon quaternary stereogenic center were generated in high yields and excellent stereoselectivities (all d.r.>95:5, up to 99% ee). PMID:25303741

  18. Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

    Shawl, A. S.; Sultan, P; H. A. Khan; C. Puri; Sharma, A.; Tripathi, R. P.; Kumar, R.; Rakesh Kumar Sharma; R. K. Sagar; Shikha Singh; Rajesh Arora; Raman Chawla; Tej Krishan; G. N. Qazi

    2006-01-01

    We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited si...

  19. Radical arylation of thiobenzanilides by aryldiazonium salts in the presence of ferrocene

    The radical chain thiophilic arylation of thiobenzanilide and thiobenz-p-anisidide by phenyl- and p-methoxyphenyldiazonium tetrafluoroborides was carried out using ferrocene as the catalyst. The corresponding s-arylisothiobenzanilides were obtained in high yield. p-Nitrophenyldiazonium tetrafluoroboride arylates these thiobenzanilides in the absence of ferrocene, presumably also by a radical mechanism; the thioamide is the catalyst for decomposition of the aryldiazonium cation. s-Arylisothiobenzanilides containing electron-withdrawing substituents on the aniline ring undergo hydrolysis under the reaction conditions

  20. Synthesis and antimicrobial activity of some new 2-(3-(4-Aryl-1-phenyl-1H-pyrazol-4-yl chroman-4-ones

    O Prakash

    2011-01-01

    Full Text Available Seven new 2-(3-(4-aryl-1-phenyl-1H-pyrazol-4-yl chroman-4-ones (4a-4g have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of 1 HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole.

  1. Efficient synthesis and antimicrobial activity of some novel S-β-d-glucosides of 5-aryl-1,2,4-triazole-3-thiones derivatives.

    Ji, Dan; Lu, JunRui; Lu, BoWei; Xin, ChunWei; Mu, JiangBei; Li, JianFa; Peng, ChunYong; Bao, XiuRong

    2013-04-01

    A series of 3-S-β-d-glucosides-4-arylideneamino-5-aryl-1,2,4-triazoles were rationally designed and synthesized according to the principle of superposition of bioactive substructures by the combination of 1,2,4-triazole, Schiff base and glucosides. The structures of the target compounds have been characterized by (1)H NMR, (13)C NMR, IR, MS and HRMS. All the newly synthesized compounds have been evaluated for their antimicrobial activities in vitro against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8099) as well as Monilia albican (ATCC 10231). The bioactive assay showed that most of the tested compounds displayed variable inhibitory effects on the growth of the Gram-positive bacterial strain (Staphylococcus aureus), Gram-negative bacterial strains (Escherichia coli) and fungal strains (Monilia albican). All the target compounds exhibited better antifungal activity than antibacterial activity. Especially, compounds 6b, 6c, 6f, 6j, 6k and 6l showed excellent activity against fungus Monilia albican with MIC values of 16 μg/mL. PMID:23466234

  2. Synthesis and Antimicrobial Activity of Some New 2-(3-(4-Aryl)-1-phenyl-1H-pyrazol-4-yl) Chroman-4-ones.

    Prakash, O; Hussain, K; Aneja, K R; Sharma, C

    2011-09-01

    Seven new 2-(3-(4-aryl)-1-phenyl-1H-pyrazol-4-yl) chroman-4-ones (4a-4g) have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of (1)HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole. PMID:22923876

  3. Synthesis of Pure and N-substituted Cyclic Hydrocarbons (e.g. Pyrimidine) via Gas-Phase Ion-Molecule Reactions

    Bera, Partha P.; Peverati, Roberto; Head-Gordon, Martin; Lee, Timothy J.

    2015-08-01

    Large polyatomic carbonaceous molecules, known as polycyclic aromatic hydrocarbons, are known to exist in the outflows of carbon stars. How these large polyatomic molecules are synthesized in such exotic conditions is, thus far, unknown. Molecular ions, including positive and negative ions, are in relative abundance in the high radiation fields present under such conditions. Hence, barrierless ion-molecule interactions may play a major role in guiding molecules towards each other and initiating reactions. We study these condensation pathways to determine whether they are a viable means of forming large pure hydrocarbon molecules, and nitrogen-containing carbonaceous chains, stacks, and even cyclic compounds. By employing accurate quantum chemical methods we have investigated the processes of growth, structures, nature of bonding, mechanisms, and spectroscopic properties of the ensuing ionic products after pairing small carbon, hydrogen, and nitrogen-containing molecules. We have also studied the ion-neutral association pathways involving pure-carbon molecules e.g. acetylene, ethylene and other hydrocarbons, and their dissociation fragments in a plasma discharge as well as how nitrogen atoms are incorporated into the carbon ring during growth. Specifically, we explored the mechanisms by which the synthesis of pyrimidine will be feasible in the gas phase in conjunction with ion-mobility experiments. We have used accurate ab initio coupled cluster theory, Møller-Plesset and Z-averaged perturbation theories, density functional theory, and coupled cluster theory quantum chemical methods together with large correlation consistent basis sets in these investigations. We found that a series of hydrocarbons with a specific stoichiometric composition prefers cyclic molecule formation rather than chains. Some of the association products we investigated have large oscillator strengths for charge-transfer type electronic excitations in the near infrared and visible regions of the electromagnetic spectrum.P. P. Bera, Roberto Peverati, M. Head-Gordon, and Timothy J. Lee, Phys. Chem. Chem. Phys. 17, 1859-1869 (2015)

  4. Preparation and assessment of [99mTc]technetium aquacarbonyl complexes with 1,2-diaminoethane-N-substituted ligands for tumor detection

    Over least 15 years the complex [[99mTc](H20)3(CO)3]+ has been used as an intermediary to obtain technetium radiopharmaceuticals for applications in cardiology, neurology and oncology. Two important characteristics of this molecule are: the facility for obtaining that compound from aqueous solutions and the easiness of substituting H2O molecules by atoms of other ligand molecules. In this project we prepared new complexes [[99mTc](CMNS001-3)(H2O)(CO)3]+, where (CMNS001) = N-[(4-methoxy) benzyl]-1,2-diaminoethane, (CMNS003) = N,N'-bis-[(4-methoxy)benzyl]-1,2-diaminoethane, and assessed the uptake of these complexes in murine melanoma cancer cell B16F10 and breast cells MCF-7 and MDA-MD-231, and compared with [[99m](MIBI)6]+ uptake. In vitro uptake for both new technetium complex reached values close to 5%, for all cell lines, whereas the [[99mTc](MIBI)6]+ uptake was close to 1 %. The assessment of subcellular distribution showed high accumulation of the new complex in the membrane fraction, for MDAMB-231, while for B16F10 accumulation occurred both in membrane and cytoplasm; the concentration of [[99mTc](MIBI)6]+ was mainly in the cytoplasm portion. Biodistribution study in mice allowed to observe the capture of up to 1.6% of the administered dose per gram of tumor tissue for the complex [[99mTc](CMNS001)(H2O)(CO)3]+, whereas other organs such as heart, lung and muscle, showed uptake of about 5.6%, 6.4% and 2%, respectively. The complexes in this work showed a high rate of uptake in vitro, but was not reproduced in vivo model, which can be related to low concentration of the complexes inside the cells and reduced vascularity of tumor tissue, with lower intake of complex through the blood system. (author)

  5. Nature of phenolic compounds in coffee melanoidins.

    Coelho, Carina; Ribeiro, Miguel; Cruz, Ana C S; Domingues, M Rosrio M; Coimbra, Manuel A; Bunzel, Mirko; Nunes, Fernando M

    2014-08-01

    Phenolic compounds are incorporated into coffee melanoidins during roasting mainly in condensed form (42-62 mmol/100 g) and also in ester-linked form (1.1-1.6 mmol/100 g), with incorporation levels depending on the green coffee chlorogenic acid content. The phenolic compounds are incorporated in different coffee melanoidin populations, but mainly in those soluble in 75% ethanol (82%), a significant correlation between the amount of phenolic compounds and the amount of protein and color characteristics of the different melanoidin populations being observed. The incorporation of phenolic compounds into coffee melanoidins is a significant pathway of chlorogenic acid degradation during roasting, representing 23% of the chlorogenic acids lost. These account for the nearly 26% of the material not accounted for by polysaccharides and proteins present in coffee melanodins. The cleavage mechanism and the efficiency of alkaline fusion used to release condensed phenolics from coffee melanoidins suggest that the phenolic compounds can be linked to the polymeric material by aryl-ether, stilbene type, and/or biphenyl linkages. PMID:24998624

  6. Palladium-catalyzed enolate arylation as a key C-C bond-forming reaction for the synthesis of isoquinolines.

    Pilgrim, Ben S; Gatland, Alice E; Esteves, Carlos H A; McTernan, Charlie T; Jones, Geraint R; Tatton, Matthew R; Procopiou, Panayiotis A; Donohoe, Timothy J

    2016-01-21

    The palladium-catalyzed coupling of an enolate with an ortho-functionalized aryl halide (an α-arylation) furnishes a protected 1,5-dicarbonyl moiety that can be cyclized to an isoquinoline with a source of ammonia. This fully regioselective synthetic route tolerates a wide range of substituents, including those that give rise to the traditionally difficult to access electron-deficient isoquinoline skeletons. These two synthetic operations can be combined to give a three-component, one-pot isoquinoline synthesis. Alternatively, cyclization of the intermediates with hydroxylamine hydrochloride engenders direct access to isoquinoline N-oxides; and cyclization with methylamine, gives isoquinolinium salts. Significant diversity is available in the substituents at the C4 position in four-component, one-pot couplings, by either trapping the in situ intermediate after α-arylation with carbon or heteroatom-based electrophiles, or by performing an α,α-heterodiarylation to install aryl groups at this position. The α-arylation of nitrile and ester enolates gives access to 3-amino and 3-hydroxyisoquinolines and the α-arylation of tert-butyl cyanoacetate followed by electrophile trapping, decarboxylation and cyclization, C4-functionalized 3-aminoisoquinolines. An oxime directing group can be used to direct a C-H functionalization/bromination, which allows monofunctionalized rather than difunctionalized aryl precursors to be brought through this synthetic route. PMID:26632484

  7. On the search for potential antimycobacterial drugs: synthesis of naphthoquinoidal, phenazinic and 1,2,3-triazolic compounds and evaluation against mycobacterium tuberculosis

    Guilherme A. M., Jardim; Eduardo H. G., Cruz; Wagner O., Valena; Jarbas M., Resende; Bernardo L., Rodrigues; Daniela F., Ramos; Ronaldo N., Oliveira; Pedro E. A., Silva; Eufrnio N. da, Silva Jnior.

    2015-05-01

    Full Text Available Fifteen naphthoquinones, sixteen phenazines and fifteen aryl triazoles were synthesized and evaluated against Mycobacterium tuberculosis. Twenty five substances are reported here for the first time and, among all of the compounds evaluated, six presented MIC (minimal inhibitory concentration) values [...

  8. Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

    Shinichiro Fuse

    2013-11-01

    Full Text Available Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers.

  9. Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis

    Zuo, Zhiwei; Cong, Huan; Li, Wei; Choi, Junwon; Fu, Gregory C.; MacMillan, David W. C.

    2016-01-01

    An asymmetric decarboxylative Csp3–Csp2 cross-coupling has been achieved via the synergistic merger of photoredox and nickel catalysis. This mild, operationally simple protocol transforms a wide variety of naturally abundant α-amino acids and readily available aryl halides into valuable chiral benzylic amines in high enantiomeric excess, thereby producing motifs found in pharmacologically active agents. PMID:26849354

  10. Stereoselective Synthesis of 2-Deoxy-?-glycosides Using Anomeric O-Alkylation/Arylation

    Morris, William J.; Shair, Matthew David

    2009-01-01

    Anomeric O-alkylation/arylation is applied to the synthesis of 2-deoxy-?-glycosides. Treatment of lactols with NaH in dioxane followed by the addition of electrophiles leads to the formation of 2-deoxy-?-glycosides in high yield and high selectivity. The high ?-selectivity observed here demonstrates a powerful stereoelectronic effect for the stereoselective formation of acetals under kinetic control.

  11. Diastereo- and enantioselective intramolecular C(sp3)-H arylation for the synthesis of fused cyclopentanes.

    Martin, Nicolas; Pierre, Cathleen; Davi, Michal; Jazzar, Rodolphe; Baudoin, Olivier

    2012-04-10

    All C-H bonds are not equal: The intramolecular arylation of unactivated C(sp(3))-H bonds in the presence of a chiral Pd/binepine catalyst allows the synthesis of fused cyclopentanes efficiently and in an diastereo- and enantioselective manner (see scheme). PMID:22407525

  12. Magnetic silica supported palladium catalyst: synthesis of allyl aryl ethers in water

    A simple and benign procedure for the synthesis of aryl allyl ethers has been developed using phenols, allyl acetates and magnetically recyclable silica supported palladium catalyst in water; performance of reaction in air and easy separation of the catalyst using an external mag...

  13. Magnetic Silica Supported Copper: A Modular Approach to Aqueous Ullmann-type Amination of Aryl Halides

    One-pot synthesis of magnetic silica supported copper catalyst has been described via in situ generated magnetic silica (Fe3O4@SiO2); the catalyst can be used for the efficacious amination of aryl halides in aqueous medium under microwave irradiation.

  14. Metal-Free Approach for the Synthesis of N-Aryl Sulfoximines via Aryne Intermediate.

    Aithagani, Sravan Kumar; Dara, Saidulu; Munagala, Gurunadham; Aruri, Hariprasad; Yadav, Mahipal; Sharma, Shweta; Vishwakarma, Ram A; Singh, Parvinder Pal

    2015-11-20

    A metal-free and operationally simple N-arylation of NH-sulfoximines with aryne precursors is reported. Transition metal-free reaction conditions and shorter reaction times are the highlights of the present method. The mild optimized condition was also found to be suitable with enantiopure substrates. PMID:26562479

  15. Reductive carbonylation of aryl halides employing a two-chamber reactor

    Korsager, Signe; Taaning, Rolf H; Lindhardt, Anders T; Skrydstrup, Troels

    2013-01-01

    A protocol has been developed for conducting the palladium-catalyzed reductive carbonylation of aryl iodides and bromides using 9-methylfluorene-9-carbonyl chloride (COgen) as a source of externally delivered carbon monoxide in a sealed two-chamber system (COware), and potassium formate as the in...

  16. Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

    Shinichiro Fuse; Nobutake Tanabe; Akio Tannna; Yohei Konishi; Takashi Takahashi

    2013-01-01

    Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers.

  17. The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation

    Smith, Brenden W.; Rozelle, Sarah S.; Leung, Amy; Ubellacker, Jessalyn; Parks, Ashley; Nah, Shirley K.; French, Deborah; Gadue, Paul; Monti, Stefano; Chui, David H.K.; Steinberg, Martin H; Frelinger, Andrew L.; Michelson, Alan D; Theberge, Roger; McComb, Mark E

    2013-01-01

    This breakthrough involves the role of the aryl hydrocarbon receptor in the expansion and specification of hematopoietic progenitor cells.This work sets a precedent for the use of an in vitro platform for the clinically relevant production of blood products.

  18. Inhibition of mucin glycosylation by aryl-N-acetyl-alpha-galactosaminides in human colon cancer cells

    Specific inhibitors of the glycosylation of O-glycosidically linked glycoproteins have not previously been described. When tested for their effects on mucin glycosylation in a mucin-producing colon cancer cell line, LS174T, benzyl-, phenyl-, and p-nitrophenyl-N-acetyl-alpha-galactosaminide inhibited the formation of fully glycosylated mucin in a dose-dependent manner. Free aryl-oligosaccharides were found in the medium of treated cells labeled with [3H]glucosamine, [3H]galactose, [3H]fucose, [3H]mannosamine, or phenyl-alpha-[6-3H] N-acetylgalactosamine. UDP-Gal:GalNAc-beta 1,3-galactosyltransferase was inhibited by aryl-N-acetyl-alpha-galactosaminides but not by a number of other aryl-glycosides. Treatment with these inhibitors also causes reversible morphologic changes including formation of intercellular cysts. Aryl-N-acetyl-alpha-galactosaminides can be useful for the structural and functional studies of mucin macromolecules and other O-linked glycoproteins

  19. Pd(0)-catalyzed intramolecular ?-arylation of sulfones: domino reactions in the synthesis of functionalized tetrahydroisoquinolines.

    Sol, Daniel; Prez-Janer, Ferran; Mancuso, Raffaella

    2015-03-16

    A new strategy for the synthesis of tetrahydroisoquinolines based on the Pd(0)-catalyzed intramolecular ?-arylation of sulfones is reported. The combination of this Pd-catalyzed reaction with intermolecular Michael and aza-Michael reactions allows the development of two- and three-step domino processes to synthesize diversely functionalized scaffolds from readily available starting materials. PMID:25677083

  20. Synthesis of enaminones and their difluoroboron complexes through domino aryl migration

    Yang, Zheng; Jiang, Bo; Hao, Wen-Juan; Zhou, Peng; Tu, Shu-Jiang; Li, Guigen

    2015-01-01

    A new domino strategy for selective synthesis of enaminones and their difluoroboron complexes through aryl migration has been developed. The reaction features low-cost and readily accessible starting materials, reliable scalability, and bond-forming efficiency as well as simple one-pot operation, which makes this strategy highly viable for future applications. PMID:25475958

  1. Organocatalytic enantioselective formal arylation of azlactones using quinones as the aromatic partner.

    Li, Guofeng; Sun, Wangsheng; Li, Jingyi; Jia, Fengjing; Hong, Liang; Wang, Rui

    2015-06-30

    A new method for the catalytic enantioselective formal arylation of azlactones using quinones as the aromatic partner was developed for the first time. Under mild conditions, the domino Michael/aromatization/cyclization reaction worked well to afford the corresponding products in moderate to high yields with excellent enantioselectivities, some of which have promising cytotoxicity against cancer cells and antibacterial activities. PMID:26083993

  2. Synthesis of enaminones and their difluoroboron complexes through domino aryl migration.

    Yang, Zheng; Jiang, Bo; Hao, Wen-Juan; Zhou, Peng; Tu, Shu-Jiang; Li, Guigen

    2015-01-25

    A new domino strategy for selective synthesis of enaminones and their difluoroboron complexes through aryl migration has been developed. The reaction features low-cost and readily accessible starting materials, reliable scalability, and bond-forming efficiency as well as simple one-pot operation, which makes this strategy highly viable for future applications. PMID:25475958

  3. Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

    Farhan R. Bou-Hamdan

    2011-08-01

    Full Text Available Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.

  4. Palladium-catalyzed carbonylative sonogashira coupling of aryl bromides using near stoichiometric carbon monoxide

    Neumann, Karoline T.; Laursen, Simon R.; Lindhardt, Anders T.; Bang-Andersen, Benny; Skrydstrup, Troels

    2014-01-01

    A general procedure for the palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides is reported, using near stoichiometric amounts of carbon monoxide. The method allows a broad substrate scope in moderate to excellent yields. The formed alkynone motive serves as a platform for...

  5. Brominated Thiophenes as Precursors in the Preparation of Brominated and Arylated Anthraquinones

    Thies Thiemann

    2009-03-01

    Full Text Available Brominated anthraquinones can be synthesized directly from bromothiophenes when these are reacted with 1,4-naphthoquinones in the presence of meta-chloroperoxybenzoic acid. The bromoanthraquinones are versatile building blocks in the preparation of arylated anthraquinones and of extended π-systems with interspersed anthraquinone units.

  6. Ortho C-H Acylation of Aryl Iodides by Palladium/Norbornene Catalysis.

    Dong, Zhe; Wang, Jianchun; Ren, Zhi; Dong, Guangbin

    2015-10-19

    Reported herein is a palladium/norbornene-catalyzed ortho-arene acylation of aryl iodides by a Catellani-type C-H functionalization. This transformation is enabled by isopropyl carbonate anhydrides, which serve as both an acyl cation equivalent and a hydride source. PMID:26333071

  7. The slow dissociation rate of K-1602 contributes to the enhanced inhibitory activity of this novel alkyl-aryl-bearing fluoroketolide.

    Krokidis, Marios; Bougas, Anthony; Stavropoulou, Maria; Kalpaxis, Dimitrios; Dinos, George P

    2016-04-01

    Ketolides belong to the latest generation of macrolides and are not only effective against macrolide susceptible bacterial strains but also against some macrolide resistant strains. Here we present data providing insights into the mechanism of action of K-1602, a novel alkyl-aryl-bearing fluoroketolide. According to our data, the K-1602 interacts with the ribosome as a one-step slow binding inhibitor, displaying an association rate constant equal to 0.28 × 10(4 )M(-1) s(-1) and a dissociation rate constant equal to 0.0025 min(-1). Both constants contribute to produce an overall inhibition constant Ki equal to 1.49 × 10(-8 )M, which correlates very well with the superior activity of this compound when compared with many other ketolides or fluoroketolides. PMID:25807301

  8. Synthesis of 4-aryl-4,5-dihydro-1-indeno[1,2-]pyrimidines by Biginelli condensation and their antibacterial activities

    Ramandeep Kaur; Monika Bansal; Balbir Kaur; Tulika Mishra; Aruna Bhatia

    2011-07-01

    A simple and efficient method has been developed for the synthesis of series of 4-aryl-1,3,4,5-tetrahydro-2-indeno[1,2-]pyrimidine-2-thiones through Biginelli’s one-pot multicomponent condensation reaction via microwave irradiations. Then, these thiones were converted to their S-alkylated/aralkylated derivatives. The prepared heterocyclic products were structurally confirmed by analytical and spectral data and evaluated for their antibacterial activities. The results showed that this skeletal framework exhibited marked potency as antibacterial agents. The compound 2-(Ethylthio)-4-(4-Hydroxy-3-methoxyphenyl)-4,5-dihydro-1-indeno[1,2-]pyrimidines 4b have shown antibacterial activity towards all the seven clinical isolates used.

  9. Magnetic susceptibility and molecular structure; study of uranyl complexes with Schiff bases of 2-hydroxy-1-naphthaldehyde and some aryl amines

    Uranyl complexes of some Schiff bases obtained by condensing some aryl amines with 2-hydroxy-1-naphthaldehyde are synthesised and characterised by elemental analysis, spectral and conductivity data. All the complexes are orange-red to red in colour, microcrystalline in nature and form compounds of the type [UO2(LH)2](CH3COO)2 where (LH) is a Schiff base molecule. The bonding with the metal in the complexes takes place from hydroxyl oxygen and imine nitrogen of the ligand. It is observed that uranyl ion form 1:2 adducts with these Schiff bases. Conductivity measurements, analytical data and spectral study show that these complexes have co-ordination number eight with hexagonal bipyramid structure. All the complexes studied are spin paired, since they exhibit property of diamagnetism. Diamagnetism of complexes is discussed. (author). 24 refs., 3 tabs

  10. Synthesis and fungicidal activity of novel 2-aryl-3-(1,3,4-thiadiazolyl)-6(8)-methyl-1,3-benzoxazines.

    Tang, Zi-long; Xia, Zan-wen; Chang, Shu-hong; Wang, Zhao-xu

    2015-08-15

    A class of novel 2-aryl-3-(1,3,4-thiadiazolyl)-6(8)-methyl-1,3-benzoxazines was prepared by reactions of 2-methyl-6-((1,3,4-thiadiazolylamino)methyl)phenols or 4-methyl-2-((1,3,4-thiadiazolylamino)methyl)phenols and 2- or 4-nitrobenzaldehyde in the presence of TMSCl in refluxing toluene. The electron-donating methyl group on the benzene ring played an essential role on the reactivity of the substituted phenols, which was proved by DFT calculation. The fungicidal activity of the resultant products were also preliminarily evaluated, most of which displayed moderate to good fungicidal activity. Especially, compound 6f showed 98.0% activity against Sclerotonia sclerotiorum and Botrytis cinerea at concentration of 25μg/mL. PMID:26071637

  11. O-methylation of natural phenolic compounds based on green chemistry using dimethyl carbonate

    Prakoso, N. I.; Pangestu, P. H.; Wahyuningsih, T. D.

    2016-02-01

    The alkyl aryl ether compounds, of which methyl eugenol and veratraldehyde are the simplest intermediates can be synthesized by reacting eugenol and vanillin with the green reagent dimethyl carbonate (DMC). The reaction was carried out under mild of temperature and pressure. Excellent yields and selective products were obtained (95-96%) after a few hours. In the end of the reaction, the catalysts (base and Phase Transfer Catalyst) can be recovered and regenerated.

  12. Synthesis and in Vitro Antimicrobial Evaluation of New N-Heterocyclic Diquaternary Pyridinium Compounds

    Bianca Furdui; Georgiana Parfene; Ioana Otilia Ghinea; Rodica Mihaela Dinica; Gabriela Bahrim; Martine Demeunynck

    2014-01-01

    A series of bis-pyridinium quaternary ammonium salts (bis-PyQAs) with different aryl and heteroaryl moieties were synthesized and their antimicrobial activity investigated. The inhibition effect of the compounds was evaluated against bacteria, molds and yeasts; the activities were expressed as the minimum inhibitory concentrations (MIC). The relationships between the structure descriptors (logP, polarizability, polar surface area (2D), van der Waals area (3D)) and the biological activity of t...

  13. Brnsted Acidic Ionic Liquid Accelerated Halogenation of Organic Compounds with N-Halosuccinimides (NXS)

    Vrai?, Dejan; Jereb, Marjan; Laali, Kenneth; Stavber, Stojan

    2012-01-01

    The Brnsted-acidic ionic liquid 1-methyl-3-(4-sulfobutyl)imidazolium triflate [BMIM(SO3H)][OTf] was demonstrated to act efficiently as solvent and catalyst for the halogenation of activated organic compounds with N-halosuccinimides (NXS) under mild conditions with short reaction times. Methyl aryl ketones were converted into ?-halo and ?,?-dihaloketones, depending on the quantity of NXS used. Ketones with activated aromatic rings were selectively halogenated, however in some cases mixtures o...

  14. Brønsted Acidic Ionic Liquid Accelerated Halogenation of Organic Compounds with N-Halosuccinimides (NXS)

    Stojan Stavber; Laali, Kenneth K; Dejan Vrai?; Marjan Jereb

    2012-01-01

    The Brnsted-acidic ionic liquid 1-methyl-3-(4-sulfobutyl)imidazolium triflate [BMIM(SO3H)][OTf] was demonstrated to act efficiently as solvent and catalyst for the halogenation of activated organic compounds with N-halosuccinimides (NXS) under mild conditions with short reaction times. Methyl aryl ketones were converted into ?-halo and ?,?-dihaloketones, depending on the quantity of NXS used. Ketones with activated aromatic rings were selectively halogenat...

  15. Aromatic fluorine compounds. VII. Replacement of aromatic -Cl and -NO2 groups by -F

    Finger, G.C.; Kruse, C.W.

    1956-01-01

    Replacement of -Cl by -F in aryl chlorides with potassium fluoride has been extended from 2,4-dinitrochlorobenzene to less activated halides by the use of non-aqueous solvents, especially dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). Also replacement of -NO2 by -F in substituted nitrobenzenes was studied in DMF. As a direct result of this study, many aromatic fluorine compounds can now be obtained by a relatively simple synthetic route.

  16. A Convenient N-Arylation Route for Electron-Deficient Pyridines: The Case of ?-Extended Electrochromic Phosphaviologens.

    Reus, Christian; Stolar, Monika; Vanderkley, Jeffrey; Nebauer, Johannes; Baumgartner, Thomas

    2015-09-16

    A simple and representative procedure for the synthesis of N,N'-diarylated phosphaviologens directly from both electron-rich and electron-poor diaryliodonium salts and 2,7-diazadibenzophosphole oxide is reported. The latter are electron-deficient congeners of the widely utilized N,N'-disubstituted 4,4'-bipyridinium cations, also known as viologens, that proved to be inaccessible by the classical two-step route. The single-step preparation method for phosphaviologens described herein could be extended to genuine viologens but reached its limit when sterically demanding diaryliodonium salts were used. The studied phosphaviologens feature a significantly lowered reduction threshold as compared to all other (phospha)viologens known to date due to the combination of an extended ?-system with an electron deficient phosphole core. In addition, a considerably smaller HOMO-LUMO gap was observed due to efficient ?-delocalization across the phosphaviologen core, as well as the N-aryl substituents, which was corroborated by quantum chemical calculations. Detailed characterizations of the singly reduced radical species by EPR spectroscopy and DFT calculations verified delocalization of the radical over the extended ?-system. Finally, to gain deeper insight into the suitability of the new compounds as electroactive and electrochromic materials, multicolored proof-of-concept electrochomic devices were manufactured. PMID:26325450

  17. Pd(OAc)2/DPPF-catalysed microwave-assisted cyanide-free synthesis of aryl nitriles

    Dinesh N Sawant; Bhalchandra M Bhanage

    2014-03-01

    This study reports microwave-assisted cyanide-free synthesis of aryl nitriles from aryl halides using palladium acetate/1,1-bis(diphenylphosphino)ferrocene as a new catalyst system. Reported protocol is a rapid, cyanide-free, single step reaction, wherein formamide acts as a solvent as well as a source of cyanide. The use of microwave increases the rate of reaction substantially and it was observed that aryl nitriles can be synthesised in 50 min of microwave irradiation compared to conventional thermal heating protocol which requires 48 h.

  18. Completely N1-Selective Palladium-Catalyzed Arylation of Unsymmetric Imidazoles: Application to the Synthesis of Nilotinib

    Ueda, Satoshi; Su, Mingjuan; Buchwald, Stephen L.

    2011-01-01

    The completely N1-selective Pd-catalyzed arylation of unsymmetric imidazoles with aryl halides and triflates is described. This study showed that imidazoles have a strong inhibitory effect on the in situ formation of catalytically-active Pd(0)-ligand complex. The efficacy of the N-arylation reaction was improved drastically by the use of pre-activated solution of Pd2(dba)3 and L1. From these findings it is clear that while imidazoles can prevent binding of L1 to the Pd, once the ligand is bou...

  19. Aryl(silyl)amino group stabilized hydridosilanediols: synthesis and characterization and use for preparation of alumino(hydrido)siloxanes.

    Wang, Xiaoping; Li, Jiancheng; Chen, Shimin; Liu, Weiping; Ye, Qingsong; Zhu, Hongping

    2016-04-12

    Aryl(silyl)amino group stabilized hydridosilanediols RSiH(OH)2 (R = N(SiMe2Ph)-2,6-iPr2C6H3 (), N(SiMe3)-2,6-iPr2C6H3 (), and N(SiMe2Ph)-2,4,6-Me3C6H2 ()) were prepared from the controlled hydrolysis of the related RSiHCl2 () each in the presence of aniline as the HCl acceptor. Reactions of with AlMe3, AliBu3, AlH(iBu)2, and AlH3·NMe3, respectively, yielded alumino(hydrido)siloxanes [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAlMe(THF)]2 (), [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAliBu(THF)]2 (), [2,6-iPr2C6H3N(SiMe2Ph)Si(H)O2]3[Al(THF)]2 (), and [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAlH(THF)]2 (). The reaction of with AlMe3 gave [2,6-iPr2C6H3N(SiMe3)Si(H)OAlMe(THF)]2 (), a compound similar to . Compounds are characterized by NMR ((1)H, (13)C, and (29)Si) and IR spectroscopy and CHN elemental analysis, of which and are further studied by X-ray crystallography. Compounds and feature cyclic structures all with the skeleton core of Si2O4Al2 while compound exhibits a bicyclic structure having a core of Si3O6Al2. Melting point measurements indicated that are thermally stable bearing the geminal SiH and SiOH groups. Compounds and are thermally stable as well with the O atom-bridged SiH and AlR (R = Me, iBu, or H) groups. PMID:26975000

  20. Direct Arylation of Pyrroles via Indirect Electroreductive C-H Functionalization Using Perylene Bisimide as an Electron-Transfer Mediator.

    Sun, Guoquan; Ren, Shuya; Zhu, Xinhai; Huang, Manna; Wan, Yiqian

    2016-02-01

    The indirect electroreductive coupling of aryl halides and pyrroles was successfully conducted using a catalytic amount of perylene bisimide as a mediator in 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide ([EMIM]NTf2)/DMSO. PMID:26800089

  1. Cooperative effect of silver in copper-catalyzed trifluoromethylation of aryl iodides using Me3SiCF3

    Weng, Zhiqiang

    2011-06-13

    An effective model of cooperative effect of silver for the coppercatalyzed trifluoromethylation of activated and unactivated aryl iodides to trifluoromethylated arenes using Me3SiCF3 was achieved with a broad substrate scope. © 2011 American Chemical Society.

  2. Allium Discoloration: Color Compounds Formed during Pinking of Onion and Leek.

    Kubec, Roman; Urajov, Petra; Lacina, Ond?ej; Hajlov, Jana; Kuzma, Marek; Zpal, Jakub

    2015-11-25

    Structures and formation pathways of compounds responsible for pink discoloration of onion and leek were studied. A procedure was developed for the isolation and purification of the color compounds from various model systems and their identification by HPLC-DAD-MS/MS. In total, structures of 15 major color compounds were tentatively determined. It was found that the pigment is a complex mixture of highly conjugated species composed of two N-substituted 3,4-dimethylpyrrole-derived rings linked by either a methine or a propenylidine bridge. These two-ring units are further modified by various C1- and C3-side chains. Experiments with isotope-labeled thiosulfinates revealed that the methine bridge and C1-side chains originate from the methyl group of methiin, whereas the C3 units are derived from the propenyl group of isoalliin. PMID:26548475

  3. Multipurpose Compound

    1983-01-01

    Specially formulated derivatives of an unusual basic compound known as Alcide may be the answer to effective treatment and prevention of the disease bovine mastitis, a bacterial inflammation of a cow's mammary gland that results in loss of milk production and in extreme cases, death. Manufactured by Alcide Corporation the Alcide compound has killed all tested bacteria, virus and fungi, shortly after contact, with minimal toxic effects on humans or animals. Alcide Corporation credits the existence of the mastitis treatment/prevention products to assistance provided the company by NERAC, Inc.

  4. The aryl hydrocarbon receptor (AhR) inhibits vanadate-induced vascular endothelial growth factor (VEGF) production in TRAMP prostates

    Fritz, Wayne A.; Lin, Tien-Min; Richard E. Peterson

    2008-01-01

    Hypoxia-inducible factor-1 alpha (HIF-1α) and aryl hydrocarbon receptor nuclear translocator (ARNT) are basic helix-loop-helix/per-arnt-sim (PAS) family transcription factors. During angiogenesis and tumor growth, HIF-1α dimerizes with ARNT, inducing expression of many genes, including vascular endothelial growth factor (VEGF). ARNT also dimerizes with the aryl hydrocarbon receptor (AhR). AhR-null (Ahr−/−) transgenic adenocarcinoma of the mouse prostate (TRAMP) mice develop prostate tumors wi...

  5. Ortho vs ipso: site-selective Pd and norbornene-catalyzed arene C-H amination using aryl halides.

    Dong, Zhe; Dong, Guangbin

    2013-12-11

    A Pd and norbornene-catalyzed ortho-arene amination via Catellani-type C-H functionalization is reported. Aryl halides are used as substrates; N-benzoyloxyamines and isopropanol are employed as the amine source (oxidant) and reductant respectively. Examples are provided in 50-99% yields with high functional group tolerance. This method gives complementary site selectivity at the ortho- instead of ipso-position of aryl halides. PMID:24256439

  6. Aminoquinoline-assisted vinylic C-H arylation of unsubstituted acrylamide for the selective synthesis of Z olefins.

    Cheng, Xiuzhi; Chen, Zhen; Gao, Yadong; Xue, Fengtian; Jiang, Chao

    2016-03-15

    A method for Pd-catalyzed, aminoquinoline-directed arylation of vinylic C-H bonds with aryl iodides has been developed. This reaction represents a rare example of Pd-catalyzed vinylic C-H functionalization of unsubstituted acrylamide, allowing for the highly regio- and stereoselective preparation of Z-olefins. High tolerance to functional groups is observed with good yields and excellent selectivity. It offers a complementary synthetic method to traditional pathways for Z-olefins. PMID:26932744

  7. Metal-free arylation of pyrimidines through a photochemical process.

    Ruch, Jonas; Aubin, Ariane; Erbland, Guillaume; Fortunato, Audrey; Goddard, Jean-Philippe

    2016-01-28

    Pyrimidinyl and pyrazinyl radicals were generated under moderate energetic irradiation conditions (UVA), and proved to be prompt to undergo C-C bond formation processes. Hetero-biaryl derivatives were obtained in good to high yields with highly interesting functional group selectivities. Bis hetero-biaryls were also easily accessible leading to original compounds, ready for further transformations. Experiments supporting radical processes have been reported. PMID:26728790

  8. Soluble N-Substituted Organosilane Polybenzimidazoles

    Klaehn, J. R.; Luther, T. A.; Orme, C. J.; Jones, M. G.; Wertsching, A. K.; Peterson, E. S.

    2007-10-01

    Six organosilane derivatives were synthesized, and are more soluble in common organic solvents (tetrahydrofuran and chloroform) than the parent polybenzimidazole. Our polymer modification pathway provides a straightforward synthesis that can be carried out at room temperature and give reasonable yields. Solution 1H NMR spectra of both the parent and deprotonated polybenzimidazoles are reported. Based upon the NMR analysis in CDCl3, nearly all of the benzimidazole N-H positions are substituted by the organosilane moieties. Some of the modified polymers have similar thermal properties compared to the parent polymer, and the average molecular weights are higher for the substituted polybenzimidazoles than the parent PBI.

  9. Rh(I)-Catalyzed Arylation of Heterocycles via C-H Bond Activation: Expanded Scope Through Mechanistic Insight

    Lewis, Jared; Berman, Ashley; Bergman, Robert; Ellman, Jonathan

    2007-07-18

    A practical, functional group tolerant method for the Rh-catalyzed direct arylation of a variety of pharmaceutically important azoles with aryl bromides is described. Many of the successful azole and aryl bromide coupling partners are not compatible with methods for the direct arylation of heterocycles using Pd(0) or Cu(I) catalysts. The readily prepared, low molecular weight ligand, Z-1-tert-butyl-2,3,6,7-tetrahydrophosphepine, which coordinates to Rh in a bidentate P-olefin fashion to provide a highly active yet thermally stable arylation catalyst, is essential to the success of this method. By using the tetrafluoroborate salt of the corresponding phosphonium, the reactions can be assembled outside of a glove box without purification of reagents or solvent. The reactions are also conducted in THF or dioxane, which greatly simplifies product isolation relative to most other methods for direct arylation of azoles employing high-boiling amide solvents. The reactions are performed with heating in a microwave reactor to obtain excellent product yields in two hours.

  10. Simple preparation of new N-aryl-N-(3-indolmethyl acetamides and their spectroscopic analysis

    José A. Henao

    2009-12-01

    Full Text Available To prepare new indolic molecules and characterize them by spectroscopic methods. Materials and methods: All reagentswere purchased from Aldrich, commercial grade. The purity of the products and the composition of the reaction mixtures were monitoredby thin layer chromatography over Silufol UV254 0.25 mm-thick chromatoplates. Product isolation and purification were performed bycolumn chromatography (SiO2, using ethyl acetate-petroleum ether mixtures as eluents. Results. The synthesis of new N-aryl-N-(3-indolmethyl acetamides based on first step iminization reaction of indol-3-carbaldehyde is accomplished. The structures of the C-3substituted indoles were confirmed by 1H-NMR and 13C-NMR studies supported by inverse-detected 2D NMR experiments and alsothrough monocrystal X-ray diffraction. Conclusions. An efficient, economic, and fast synthetic route was designed to the construction ofthe N-aryl-N-(3-indolmethyl acetamides, structural analogues of some alkaloids.

  11. [18F]fluorination/decarbonylation: new route to aryl [18F]fluorides

    A new route to aryl [18F]fluorides without electron withdrawing ring substituents has been developed. [18F]Fluorobenzaldehydes, prepared from no-carrier-added (NCA) [18F]fluoride using nucleophilic aromatic substitution of fluoro or nitro groups, were decarbonylated using palladium on charcoal (Pd-C). By this approach 2-methoxy-4-nitrobenzaldehyde was converted to NCA 3-[18F]fluorophenol and 4-fluoro-2-methoxy-5-methylbenzaldehyde to carrier-added (CA) 3-[18]fluoro-4-methylphenol. Overall synthesis time was about 2 h. Since the 4-fluoro-2-methoxy-5-methylbenzaldehyde was in turn prepared by methylation and regiospecific formylation of 3-fluoro-4-methylphenol, the overall process represents use of a removable activating group for nucleophilic aromatic substitution with [18F]fluoride for preparation of CA and NCA aryl [18F]fluorides. (author)

  12. 3D shapes of aryl(dihydro)naphthothiophenes: a comprehensive and structural study.

    Boufroura, H; Souibgui, A; Gaucher, A; Marrot, J; Pieters, G; Aloui, F; Ben Hassine, B; Clavier, G; Prim, D

    2015-11-28

    Convenient access to new aryl(dihydro)naphthothiophenes is described using a common β-chloroacrolein derivative. Our strategy is based on the construction of a condensed thiophene ring prior to a Suzuki-Miyaura coupling and allowed installing various substituents at the molecular platform. The overall shapes of these architectures were confirmed by X-ray analyses and were in good agreement with theoretical calculations. It has been established that the relative orientation between all fragments that composed molecules within this series is strongly related to both steric and electronic factors. Contribution of these key parameters revealed to be crucial to rationalize attempts to prepare fluorenone and fluorene derivatives from aryl(dihydro)naphthothiophene platforms. PMID:26365700

  13. The convenient preparation of stable aryl-coated zerovalent iron nanoparticles.

    Guselnikova, Olga A; Galanov, Andrey I; Gutakovskii, Anton K; Postnikov, Pavel S

    2015-01-01

    A novel approach for the in situ synthesis of zerovalent aryl-coated iron nanoparticles (NPs) based on diazonium salt chemistry is proposed. Surface-modified zerovalent iron NPs (ZVI NPs) were prepared by simple chemical reduction of iron(III) chloride aqueous solution followed by in situ modification using water soluble arenediazonium tosylate. The resulting NPs, with average iron core diameter of 21 nm, were coated with a 10 nm thick organic layer to provide long-term protection in air for the highly reactive zerovalent iron core up to 180 °C. The surface-modified iron NPs possess a high grafting density of the aryl group on the NPs surface of 1.23 mmol/g. FTIR spectroscopy, XRD, HRTEM, TGA/DTA, and elemental analysis were performed in order to characterize the resulting material. PMID:26171295

  14. Pyridylidene ligand facilitates gold-catalyzed oxidative C–H arylation of heterocycles

    Hata, Kazuhiro; Ito, Hideto

    2015-01-01

    Summary Triaryl-2-pyridylidene effectively facilitates the gold-catalyzed oxidative C–H arylation of heteroarenes with arylsilanes as a unique electron-donating ligand on gold. The employment of the 2-pyridylidene ligand, which is one of the strongest electron-donating N-heterocyclic carbenes, resulted in the rate acceleration of the C–H arylation reaction of heterocycles over conventional ligands such as triphenylphosphine and a classical N-heterocyclic carbene. In situ observation and isolation of the 2-pyridylidene-gold(III) species, as well as a DFT study, indicated unusual stability of gold(III) species stabilized by strong electron donation from the 2-pyridylidene ligand. Thus, the gold(I)-to-gold(III) oxidation process is thought to be facilitated by the highly electron-donating 2-pyridylidene ligand. PMID:26877796

  15. Palladium(II) Aryl-amido Complexes of Diphosphinoazines in Unsymmetrical PNP' Pincer-type Configuration

    Storch, Jan; Čermák, Jan; Pošta, Martin; Sýkora, Jan; Císařová, I.

    2008-01-01

    Roč. 693, č. 18 (2008), s. 3029-3034. ISSN 0022-328X R&D Projects: GA ČR GA203/01/0554; GA ČR GA203/06/0738; GA MŠk(CZ) LC06070 Institutional research plan: CEZ:AV0Z40720504 Keywords : diphosphinoazines * pincer complexes * aryl-amido complexes Subject RIV: CC - Organic Chemistry Impact factor: 1.866, year: 2008

  16. Microwave-Assisted Cyanation of an Aryl Bromide Directly on a Metal-Organic Framework

    Kim, Min; Garibay, Sergio J.; Cohen, Seth M.

    2011-01-01

    A microwave-assisted postsynthetic modification (PSM) reaction on a metal-organic framework (MOF) has been realized. Cyanation of the Zr4+-based UiO-66-Br was achieved with CuCN and microwave irradiation to produce UiO-66-CN. This protocol represents a significant example of PSM modification on an aryl halide MOF producing a cyano-functionalized MOF.

  17. Replacing conventional carbon nucleophiles with electrophiles: nickel-catalyzed reductive alkylation of aryl bromides and chlorides.

    Everson, Daniel A; Jones, Brittany A; Weix, Daniel J

    2012-04-11

    A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (-OH, -NHTs, -OAc, -OTs, -OTf, -COMe, -NHBoc, -NHCbz, -CN, -SO(2)Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture. The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki-Miyaura, Stille, and Hiyama-Denmark reactions. Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R-X) and no reaction at the nucleophilic carbon (R-[M]) for organoboron (-Bpin), organotin (-SnMe(3)), and organosilicon (-SiMe(2)OH) containing organic halides (X-R-[M]). A Hammett study showed a linear correlation of σ and σ(-) parameters with the relative rate of reaction of substituted aryl bromides with bromoalkanes. The small ρ values for these correlations (1.2-1.7) indicate that oxidative addition of the bromoarene is not the turnover-frequency determining step. The rate of reaction has a positive dependence on the concentration of alkyl bromide and catalyst, no dependence upon the amount of zinc (reducing agent), and an inverse dependence upon aryl halide concentration. These results and studies with an organic reductant (TDAE) argue against the intermediacy of organozinc reagents. PMID:22463689

  18. Diastereoselective metal-catalyzed synthesis of C-aryl and C-vinyl glycosides.

    Nicolas, Lionel; Angibaud, Patrick; Stansfield, Ian; Bonnet, Pascal; Meerpoel, Lieven; Reymond, Sébastien; Cossy, Janine

    2012-10-29

    Cobalt, the catalyst of choice: The diastereoselective cobalt-catalyzed cross-coupling of 1-bromo glycosides and aryl or vinyl Grignard reagents is described. A convenient and inexpensive catalyst, [Co(acac)(3)]/tmeda (acac = acetylacetonate, tmeda = N,N'-tetramethylethylenediamine), gives full α selectivity in the mannose and galactose series, and an α selectivity in the glucose series with α/β ratios of 1.3:1-3:1. PMID:23023954

  19. Nickel-Catalyzed Regiodivergent Opening of Epoxides with Aryl Halides: Co-Catalysis Controls Regioselectivity

    Zhao, Yang; Weix, Daniel J.

    2013-01-01

    Epoxides are versatile intermediates in organic synthesis, but have rarely been employed in cross-coupling reactions. We report that bipyridine-ligated nickel can mediate the addition of functionalized aryl halides, a vinyl halide, and a vinyl triflate to epoxides under reducing conditions. For terminal epoxides, the regioselectivity of the reaction depends upon the co-catalyst employed. Iodide co-catalysis results in opening at the less hindered position via an iodohydrin intermediate. Titan...

  20. Brnsted acid catalyzed direct oxidative arylation of 1,4-naphthoquinone

    Katarzyna Kap?on

    2014-01-01

    Full Text Available An inexpensive straightforward approach to direct oxidative twofold C-H arylation of 1,4-naphthoquinone catalyzed by readily available Brnsted acids was developed. Under the simple and easily achievable reaction conditions, electron-rich aromatics undergo Friedel-Crafts type functionalization to furnish 2-arylonaphthoquinones in good yields. The attempt to rationalize the scope and limitation of the approach based on desktop PC DFT calculation and reactivity indexes theory was taken up.

  1. Microwave-Assisted Synthesis of Some 3,5-Arylated 2-Pyrazolines

    Hassan Ghasemnejad; Davood Azarifar

    2003-01-01

    Condensation of 2-acetylnaphthalene with benzaldehydes under microwave irradiation affords chalcones which undergo facile and clean cyclizations with hydrazines RNHNH2 (R= H, Ph, Ac) to afford 3,5-arylated 2-pyrazolines in quantitative yields, also under microwave irradiation and in the presence of dry AcOH as cyclizing agent. The results obtained indicate that, unlike classical heating, microwave irradiation results in higher yields, shorter reaction times (2-12 min.) and cleaner reactions.

  2. Microwave-Assisted Synthesis of Some 3,5-Arylated 2-Pyrazolines

    Hassan Ghasemnejad

    2003-07-01

    Full Text Available Condensation of 2-acetylnaphthalene with benzaldehydes under microwave irradiation affords chalcones which undergo facile and clean cyclizations with hydrazines RNHNH2 (R= H, Ph, Ac to afford 3,5-arylated 2-pyrazolines in quantitative yields, also under microwave irradiation and in the presence of dry AcOH as cyclizing agent. The results obtained indicate that, unlike classical heating, microwave irradiation results in higher yields, shorter reaction times (2-12 min. and cleaner reactions.

  3. Photoinduced intramolecular substitution reaction of aryl halide with carbonyl oxygen of amide group

    Park, Y T; Kim, M S; Kwon, J H

    2002-01-01

    Photoreaction of N-(o-halophenyl)acetamide in basic acetonitrile produces an intramolecular substituted product, 2-methylbenzoxazole in addition to reduced product, acetanilide, whereas photoreaction of N-(o-halobenzyl)acetamide affords a reduced product, N-benzylacetamide only. On the basis of preparative reaction, kinetics, and UV/vis absorption behavior, an electrophilic aromatic substitution of aryl halide with oxygen of its amide bond are proposed.

  4. Synthesis and Antifungal Evaluation of 1-Aryl-2-dimethyl-aminomethyl-2-propen-1-one Hydrochlorides

    Mehmet Emin Topaloglu; Medine Gulluce; Oztekin Algul; Ebru Mete; Halise Inci Gul; Cavit Kazaz; Sinan Bilginer

    2011-01-01

    The development of resistance to current antifungal therapeutics drives the search for new effective agents. The fact that several acetophenone-derived Mannich bases had shown remarkable antifungal activities in our previous studies led us to design and synthesize some acetophenone-derived Mannich bases, 1-8 and 2-acetylthiophene-derived Mannich base 9, 1-aryl-2-dimethylaminomethyl-2-propen-1-one hydrochloride, to evaluate their antifungal activities. The designed chemical structures have α,β...

  5. ROLE OF THE ARYL HYDROCARBON RECEPTOR (AHR) IN LUNG INFLAMMATION1

    Beamer, Celine A.; Shepherd, David M.

    2013-01-01

    Millions of individuals worldwide are afflicted with acute and chronic respiratory diseases, causing temporary and permanent disabilities and even death. Oftentimes, these diseases occur as a result of altered immune responses. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, acts as a regulator of mucosal barrier function and may influence immune responsiveness in the lungs through changes in gene expression, cell-cell adhesion, mucin production, and cytokine exp...

  6. Iridium-catalyzed direct arene C-H bond amidation with sulfonyl- and aryl azides.

    Lee, Donggun; Kim, Youngchan; Chang, Sukbok

    2013-11-01

    Iridium-catalyzed direct ortho C-H amidation of arenes has been shown to work well with sulfonyl- and aryl azides as the nitrogen source. The reaction proceeds efficiently with a broad range of substrates bearing conventional directing groups with excellent functional group compatibility under mild conditions. In addition, substrates forming not only 5- but also 6-membered iridacycle intermediates undergo the C-H amidation with high selectivity. PMID:24079849

  7. Restricted utility of aryl isoprenoids as indicators of photic zone anoxia

    J.S. Sinninghe Damsté; Koopmans, M P; S. Schouten; Kohnen, M.E.L.

    1996-01-01

    In a North Sea oil, the carotenoid derivatives -carotene, -isorenieratane, and isorenieratane were identified, together with a series of aryl isoprenoids with a 2,3,6-trimethyl substitution pattern for the aromatic ring. The 13C values of -carotene and -isorenieratane are similar, whereas isorenieratane is ca. 15% heavier. This suggests that -isorenieratane is not derived from -isorenieratane biosynthesised by Chlorobiaceae, but from aromatisation of -carotene. This was confirmed by laborator...

  8. Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

    Grzegorz Mlostoń; Paulina Grzelak; Maciej Mikina; Anthony Linden; Heinz Heimgartner

    2015-01-01

    Selected hetaryl and aryl thioketones react with acetylenecarboxylates under thermal conditions in the presence of LiClO4 or, alternatively, under high-pressure conditions (5 kbar) at room temperature yielding thiopyran derivatives. The hetero-Diels–Alder reaction occurs in a chemo- and regioselective manner. The initially formed [4 + 2] cycloadducts rearrange via a 1,3-hydrogen shift sequence to give the final products. The latter were smoothly oxidized by treatment with mCPBA to the corresp...

  9. Anaerobic Aryl Reductive Dehalogenation of Halobenzoates by Cell Extracts of Desulfomonile tiedjei

    DeWeerd, Kim A.; Suflita, Joseph M.

    1990-01-01

    We studied the transformation of halogenated benzoates by cell extracts of a dehalogenating anaerobe, Desulfomonile tiedjei. We found that cell extracts possessed aryl reductive dehalogenation activity. The activity was heat labile and dependent on the addition of reduced methyl viologen, but not on that of reduced NAD, NADP, flavin mononucleotide, flavin adenine dinucleotide, desulfoviridin, cytochrome c3, or benzyl viologen. Dehalogenation activity in extracts was stimulated by formate, C...

  10. Dichotomy in regioselectivity of Pd-catalyzed direct C-H arylation of protected uracils

    Čerňová, Miroslava; Hocek, Michal

    Praha : Institute of Organic Chemistry and Biochemistry AS CR, v. v. i., 2011 - (Hocek, M.), s. 314-316 ISBN 978-80-86241-37-1. - (Collection Symposium Series. 12). [ Chemistry of Nucleic Acid Components /15./. Český Krumlov (CZ), 05.06.2011-10.06.2011] R&D Projects: GA MŠk(CZ) LC06077 Institutional research plan: CEZ:AV0Z40550506 Keywords : direct C-H arylation * uracils * pyrimidines * palladium Subject RIV: CC - Organic Chemistry

  11. Space radiation effects on poly(aryl-ether-ketone) thin films and composites

    Funk, Joan G.; Sykes, George F., Jr.

    1988-01-01

    The purpose of this study was to assess the space durability of poly(aryl-ether-ketone) (PEEK) in the forms of films and graphite fiber reinforced composites. The influence of the film's crystallinity on electron radiation stability was evaluated using X-ray diffraction, DSC, FTIR, and mechanical property tests. The mechanical properties of the composites material were evaluated after electron radiation and after electron radiation followed by thermal cycling simulating 30 years in geosynchronous orbit.

  12. Synthesis of tricyclic nitrogen heterocycles by a sequence of palladium-catalyzed N-H and C(sp3)-H arylations.

    Guyonnet, Mathieu; Baudoin, Olivier

    2012-01-01

    A range of tricyclic nitrogen heterocycles were synthesized in a straightforward and efficient manner via a sequence involving palladium-catalyzed N-arylation and C(sp(3))-H arylation as the key steps. Whereas the C(sp(3))-H arylation furnished fused 6,5,6-membered ring systems efficiently, the formation of the more strained 6,5,5-membered systems proved to be more challenging and required a subtle adjustment of the reaction conditions. PMID:22176522

  13. Antioxidant and DNA damage inhibition activities of 4-Aryl-N-(4-arylthiazol-2-yl)-5,6-dihydro-4H-1,3,4-oxadiazine-2-carboxamides

    K Shubakara; K B Umesha; N Srikantamurthy; J Chethan

    2014-11-01

    A series of 4-aryl--(4-pheny-thiazol-2-yl)-5,6-dihydro-4-1,3,4-oxadiazine-2-carboxamides were synthesized by condensing 4-aryl-5,6-dihydro-4-1,3,4-oxadiazine-2-carboxylic acid with 2-amino-4-aryl-thiazole derivatives. The newly synthesized molecules were characterized by spectral analysis and subjected to antioxidant and DNA damage inhibition studies.

  14. Microwave assisted synthesis and antimicrobial activity of novel 1-[1/2-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy-naphthalen-2/1-yl]-3-(1-phenyl-3-aryl-1H-pyrazol-4-yl-propenones

    Dongamanti Ashok

    2015-06-01

    Full Text Available A series of novel 1-[1/2-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy-naphthalen-2/1-yl]-3-(1-phenyl-3-aryl-1H-pyrazol-4-yl-propenones were design and synthesized by Click reaction followed by Claisen-Schmidt condensation under microwave irradiation and conventional heating methods. The structures of newly synthesized compounds have been established on the basis of elemental analysis, IR, 1H & 13C NMR and mass spectral data. All the compounds were screened for their antimicrobial activity.

  15. Standard molar volumes and expansibilities of 1,3-alkyl-N-substituted achiral glycolurils in water at T = (278.15 to 318.15) K and p = 0.1 MPa: A comparative analysis

    Highlights: • Densities of aqueous 1,3-dimethylglycoluril and 1,3-diethylglycoluril were measured. • Densimetric measurements were carried out at T = (278.15 to 318.15) K and ∼0.1 MPa. • Standard molar volumes and expansibilities of glycolurils in water were derived. • 1,3-DMGU has the more pronounced ability to hydrogen-bonding with water molecules. • Tendency to structure-loosening in aqueous solution increases going to 1,3-DEGU. - Abstract: Densities of aqueous solutions of achiral 1,3-dimethylglycoluril (1,3-DMGU) and 1,3-diethylglycoluril (1,3-DEGU) were measured using a hermetically sealed vibrating-tube densimeter, with an uncertainty of 1 · 10−5 g · cm−3, at T = (278.15, 288.15, 298.15, 308.15, and 318.15) K and p = (99.6 ± 0.8) kPa. The solute molality was ranged from (0.06 to 0.39) and from (0.01 to 0.07) mol · kg−1 for the aqueous 1,3-DMGU and 1,3-DEGU, respectively. The standard (at infinite dilution) molar volumes and isobaric expansibilities for the 1,3-dialkyl-N-substituted glycolurils compared in water were calculated and discussed in comparison with the previously derived molar enthalpies and heat capacities of their dissolution (hydration). The temperature-dependent behavior of packing-related hydration effects was described taking into account the structural features of a solute molecule

  16. Compound odontoma

    Monica Yadav

    2012-01-01

    Full Text Available Odontomas have been extensively reported in the dental literature, and the term refers to tumors of odontogenic origin. Though the exact etiology is still unknown, the postulated causes include: local trauma, infection, inheritance and genetic mutation. The majority of the lesions are asymptomatic; however, may be accompanied with pain and swelling as secondary complaints in some cases. Here, we report a case of a compound odontome in a 14 year old patient.

  17. General Copper-Catalyzed Coupling of Alkyl-, Aryl-, and Alkynylaluminum Reagents with Organohalides.

    Shrestha, Bijay; Thapa, Surendra; Gurung, Santosh K; Pike, Ryan A S; Giri, Ramesh

    2016-02-01

    We report the first example of a very general Cu-catalyzed cross-coupling of organoaluminum reagents with organohalides. The reactions proceed for the couplings of alkyl-, aryl-, and alkynylaluminum reagents with aryl and heteroaryl halides and vinyl bromides, affording the cross-coupled products in good to excellent yields. Both primary and secondary alkylaluminum reagents can be utilized as organometallic coupling partners. These reactions are not complicated by β-hydride elimination, and as a result rearranged products are not observed with secondary alkylaluminum reagents even for couplings with heteroaryl halides under "ligand-free" conditions. Radical clock experiment with a radical probe and relative reactivity study of Ph3Al with two haloarenes, 1-bromonaphthalene and 4-chlorobenzonitrile, having two different redox potentials indicates that the reaction does not involve free aryl radicals and radical anions as intermediates. These results combined with the result of the Hammett plot obtained by reacting Ph3Al with iodoarenes containing p-H, p-Me, p-F, and p-CF3 substituents, which shows a linear curve (R(2) = 0.99) with a ρ value of +1.06, suggest that the current transformation follows an oxidative addition-reductive elimination pathway. PMID:26735748

  18. Photosensitized oxidation of aryl benzyl sulfoxides. Evidence for nucleophilic assistance to the C-s bond cleavage of aryl benzyl sulfoxide radical cations.

    Del Giacco, Tiziana; Lanzalunga, Osvaldo; Lapi, Andrea; Mazzonna, Marco; Mencarelli, Paolo

    2015-02-20

    The radical cations of a series of aryl benzyl sulfoxides (4-X-C6H4CH2SOC6H4Y(+)) have been generated by photochemical oxidation of the parent sulfoxides sensitized by 3-cyano-N-methylquinolinium perchlorate (3-CN-NMQ(+)ClO4(-)). Steady-state photolysis experiments showed the prevailing formation of benzylic products deriving from the C-S fragmentation in the radical cations, together with sulfur-containing products. Formation of sulfoxide radical cations was unequivocally established by laser flash photolysis experiments showing the absorption bands of 3-CN-NMQ() (?max = 390 nm) and of the radical cations (?max = 500-620 nm). The decay rate constants of radical cations, determined by LFP experiments, decrease by increasing the electron-donating power of the arylsulfinyl Y substituent and to a smaller extent by increasing the electron-withdrawing power of the benzylic X substituent. A solvent nucleophilic assistance to the C-S bond cleavage has been suggested, supported by the comparison of substituent effects on the same process occurring in aryl tert-butyl sulfoxide radical cations. DFT calculations, performed to determine the bond dissociation free energy in the radical cations, the transition state energies associated with the unimolecular C-S bond cleavage, and the charge and spin delocalized on their structures, were also useful to endorse the nucleophilic assistance to the C-S scission. PMID:25601185

  19. Synthesis of N-Aryl-2-allyl Pyrrolidines via Palladium-catalyzed Carboamination Reactions of γ-(N-Arylamino)alkenes with Vinyl Bromides

    Ney, Joshua E.; Hay, Michael B.; Yang, Qifei; Wolfe, John P.

    2005-01-01

    A palladium-catalyzed carboamination reaction of γ-N-arylamino alkenes with vinyl bromides that affords N-aryl-2-allyl pyrrolidines is described. These reactions proceed with high diastereoselectivity for the formation of trans-2,3- and cis-2,5-disubstituted pyrrolidines. Conditions for a tandem N-arylation/carboamination sequence that leads to the formation of an N-aryl-2-allyl pyrrolidine or indoline via the coupling of a primary γ-amino alkene, an aryl bromide, and a vinyl bromide are also...

  20. Design, Synthesis, Characterization and Anticancer Prope rties of Novel 2-Chloro- N -(Aryl Substituted Acetamide Derivatives of 5-[2-(4- Methoxyphenyl Pyridin-3-yl]-1, 3, 4-Oxadiazole-2-Thiol

    Adimule Vinayak

    2014-12-01

    Full Text Available In this linear synthesis, novel different 2-chloro N-aryl substitutedacetamide derivatives of 5-[2-(4-methoxyphenyl pyridin-3-yl]-1, 3, 4-oxadiazole-2-thiol have been synthesized and screened for their cytotoxicity on PANC-1, HepG2and MCF7cell lines and obtained the IC50and CC50values.All the synthesized compounds were characterized by LCMS, IR, 1H and 13C (proton and Carbon 13 spectroscopies and elemental analysis. These compounds were evaluated for invitroanticancer activity on three different human leukemic cell lines, namely PANC-1,HepG2and MCF7.In total five compounds were synthesized and studied for their MTT assay. Among five synthesized novel compounds, the compound N-[5-(4-Methoxy-phenyl-pyridin-2-yl]-2-{5-[2-(4-methoxy-phenyl-pyridin-3-yl][1,3,4]oxadiazol-2 ylsulfanyl}-acetamide6eis highly cytotoxic on PANC-1and HepG2cell lines having IC50of 4.6?M and 2.2?M respectively whereas the compound 6cis moderately cytotoxic on MCF7having IC5015.5?M respectively. Rest all the compounds showed less cytotoxicity on all the three cell lines as compared with the standard 5-FU.

  1. Sequential one-pot addition of excess aryl-Grignard reagents and electrophiles to O-alkyl thioformates.

    Murai, Toshiaki; Morikawa, Kenta; Maruyama, Toshifumi

    2013-09-23

    The sequential addition of aromatic Grignard reagents to O-alkyl thioformates proceeded to completion within 30?s to give aryl benzylic sulfanes in good yields. This reaction may begin with the nucleophilic attack of the Grignard reagent onto the carbon atom of the O-alkyl thioformates, followed by the elimination of ROMgBr to generate aromatic thioaldehydes, which then react with a second molecule of the Grignard reagent at the sulfur atom to form arylsulfanyl benzylic Grignard reagents. To confirm the generation of aromatic thioaldehydes, the reaction between O-alkyl thioformates and phenyl Grignard reagent was carried out in the presence of cyclopentadiene. As a result, hetero-Diels-Alder adducts of the thioaldehyde and the diene were formed. The treatment of a mixture of the thioformate and phenyl Grignard reagent with iodine gave 1,2-bis(phenylsulfanyl)-1,2-diphenyl ethane as a product, which indicated the formation of arylsulfanyl benzylic Grignard reagents in the reaction mixture. When electrophiles were added to the Grignard reagents that were generated in?situ, four-component coupling products, that is, O-alkyl thioformates, two molecules of Grignard reagents, and electrophiles, were obtained in moderate-to-good yields. The use of silyl chloride or allylic bromides gave the adducts within 5?min, whereas the reaction with benzylic halides required more than 30?min. The addition to carbonyl compounds was complete within 1?min and the use of lithium bromide as an additive enhanced the yields of the four-component coupling products. Finally, oxiranes and imines also participated in the coupling reaction. PMID:23946145

  2. Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents.

    El-Hashash, Maher A; Rizk, Sameh A; Atta-Allah, Saad R

    2015-01-01

    A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data. PMID:26690393

  3. Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents

    Maher A. El-Hashash

    2015-12-01

    Full Text Available A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923, (ATCC 10987, (ATCC 274, and (SM514. The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data.

  4. Kinetico-mechanistic studies on the formation of seven-membered [C,N]-platinacycles: the effect of methyl or fluoro substituents on the aryl ancillary ligands.

    Crespo, Margarita; Font-Bardia, Mercè; Martínez, Manuel

    2015-12-01

    The reactions of dinuclear [Pt2(4-RC6H4)4(μ-SEt2)2] (R = Me or F), or mononuclear [Pt(4-RC6H4)2(SMe2)2] (R = Me or H), platinum(ii) compounds with imines of the general formula 2-X,6-YC6H3CH[double bond, length as m-dash]NCH2Ph (X = Br, Y = F; X = Cl, Y = F; X = Br, Y = H) produced seven-membered [C,N]-platinacycles. The reaction consists of the initial formation of cyclometallated platinum(iv) compounds followed by a three step process: reductive elimination, isomerisation of the resulting non-cyclometallated intermediate and a final cycloplatination process. Combined (1)H NMR and UV-Vis kinetico-mechanistic studies indicated that the rate determining step of the process depends on the nature of the aryl-Pt ligand (phenyl, p-tolyl or p-fluorophenyl). PMID:26158624

  5. 5-Lipoxygenase inhibitors: synthesis and structure-activity relationships of a series of 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-ones.

    Bhatia, P A; Brooks, C D; Basha, A; Ratajczyk, J D; Gunn, B P; Bouska, J B; Lanni, C; Young, P R; Bell, R L; Carter, G W

    1996-09-27

    Synthetic routes were developed to access a variety of novel 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-one analogs which were evaluated as 5-lipoxygenase (5-LO) inhibitors. The parent structure, 1-phenylperhydro-1,2,4-triazin-3-one (4), was found to be a selective inhibitor of 5-LO in broken cell, intact cell, and human blood assays with IC50 values of 5-21 microM. In a rat anaphylaxis model, 4 blocked leukotriene formation with an ED50 = 7 mg/kg when administered orally. Compound 4 exhibited selectivity for inhibition of 5-LO with little activity against related enzymes: 12-LO from human platelets, 15-LO from soybean, and cyclooxygenase (COX) from sheep seminal vesicle. In pilot subacute toxicity testing, 4 did not produce methemoglobinemia in rats (400 mg/kg po daily for 9 days) or in dogs (200 mg/kg po daily for 28 days). These results indicated that the triazinone structure provided a 5-LO inhibitor template devoid of the toxicity problems observed in the related phenidone (1) and pyridazinone (3) classes of 5-LO inhibitors. The parent compound 4 is a selective, orally bioavailable 5-LO inhibitor which can serve as a useful reference standard for in vivo pharmacological studies involving leukotriene-mediated phenonmena. PMID:8831760

  6. Synthesis, Central Nervous System Activity and Structure-Activity Relationships of Novel 1-(1-Alkyl-4-aryl-4,5-dihydro-1H-imidazo-3-substituted Urea Derivatives

    Elżbieta Szacoń

    2015-02-01

    Full Text Available A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a–3h were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a and 1b and appropriate benzyl-, phenethyl-isocyanate or ethyl 4-isocyanatobenzoate and ethyl isocyanatoacetate 2 in dichloromethane. Derivatives 4c and 4g resulted from the conversion of 3c and 3g into the respective amides due to action of an aqueous ammonia solution. The results obtained in this study, based on literature data suggest a possible involvement of serotonin system and/or the opioid system in the effects of tested compounds, and especially in the effect of compound 3h. The best activity of compound 3h may be primarily attributed to its favourable ADMET properties, i.e., higher lipophilicity (related to lower polar surface area and greater molecular surface, volume and mass than for other compounds and good blood-brain permeation. This compound has also the greatest polarizability and ovality. The HOMO and LUMO energies do not seem to be directly related to activity.

  7. Synthesis, central nervous system activity and structure-activity relationships of novel 1-(1-Alkyl-4-aryl-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives.

    Szacoń, Elżbieta; Rządkowska, Marzena; Kaczor, Agnieszka A; Kędzierska, Ewa; Fidecka, Sylwia; Matosiuk, Dariusz

    2015-01-01

    A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a-3h were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a and 1b and appropriate benzyl-, phenethyl-isocyanate or ethyl 4-isocyanatobenzoate and ethyl isocyanatoacetate 2 in dichloromethane. Derivatives 4c and 4g resulted from the conversion of 3c and 3g into the respective amides due to action of an aqueous ammonia solution. The results obtained in this study, based on literature data suggest a possible involvement of serotonin system and/or the opioid system in the effects of tested compounds, and especially in the effect of compound 3h. The best activity of compound 3h may be primarily attributed to its favourable ADMET properties, i.e., higher lipophilicity (related to lower polar surface area and greater molecular surface, volume and mass than for other compounds) and good blood-brain permeation. This compound has also the greatest polarizability and ovality. The HOMO and LUMO energies do not seem to be directly related to activity. PMID:25730390

  8. Compound odontoma

    José Marcelo Vargas Pinto

    2008-01-01

    Full Text Available Odontomas are the most common types of odontogenic tumors, as they are considered more as a developmental anomaly (hamartoma than as a true neoplasia. The aim of the present study is to describe a clinical case of compound odontoma, analyzing its most commonsigns, its region of location, the decade of life and patient’s gender, disorders that may occur as well as the treatment proposed. In order to attain this objective, the method was description of the present clinical case and bibliographic revision, arriving at the result that the treatment for this type of lesion invariably is surgical removal (enucleation and curettage and the prognosis is excellent. The surgical result was followed up in the post-operative period by radiographic exam, and it was possible to conclude that there was complete cicatrization and tissue repair.

  9. Peroxidative metabolism of carcinogenic N-arylhydroxamic acids: implications for tumorigenesis.

    Malejka-Giganti, D.; Ritter, C L

    1994-01-01

    Peroxidative oxidations of chemical carcinogens including N-substituted aryl compounds could result in their metabolic activation because the products react with cellular molecules and lead to cytotoxicity, mutagenicity, and carcinogenicity. In vivo, peroxidative activities are chiefly of neutrophilic leukocyte origin. Neutrophils may be attracted to the site(s) of exposure to carcinogen and, via phagocytosis and respiratory burst, release oxidants that catalyze carcinogen activation and/or c...

  10. Theoretical evaluation of medicinal properties for some of N-aryl-3-hydroxypyridine-4-ones derivative compounds

    Mohsen Oftadeh

    2014-02-01

    Full Text Available Nowadays, the bidentate ligands 3-hydroxypyridin-4-ones (HPOs as orally active iron chelating agents have been demonstrated to possess potentials for the treatment of some of the human diseases such as iron-overload in thalassaemia patients and malaria. In this research, a series of HPOs with different substitutes and positions were theoretically investigated in order to extract and predict their partition coefficient values (LogP which were experimentally determined in an aqueous/octanol system. The effective electronic parameters on logP were also investigated. The results show that the type of method, basis set, and the solvent do not basically affect on the logP values. But some parameters such as hydrophobicity, polarizability, and orbital electronic charge density (HOMO and LUMO are effective on logP values.

  11. Synthesis of 2,3-epoxy-1-phenyl-3-aryl-1-propanone by combination of phase transfer catalyst and ultrasound irradiation

    Ji-Tai Li

    2009-03-01

    Full Text Available Seven 2,3-epoxy-1-phenyl-3-aryl-1-propanones were synthesized via epoxidation of thecorresponding 1-phenyl-3-aryl-2-propen-1-ones with 30% aqueous hydrogen peroxide in 74-99% yields usingbenzyldimethyltetradecylammonium chloride as phase transfer catalyst under ultrasound irradiation.

  12. Application of nano SnO2 as a green and recyclable catalyst for the synthesis of 2-aryl or alkylbenzoxazole derivatives under ambient temperature

    Seyed Mohammad Vahdat; Shima Ghafouri Raz; Saeed Baghery

    2014-05-01

    Application of nano SnO2 as an efficient and benign catalyst has been explored for the synthesis of 2-aryl or alkylbenzoxazole derivatives via condensation reaction of aldehyde with 2-aminophenol. The reactions proceed under heterogeneous and mild conditions in ethanol at room temperature to provide 2-aryl or alkylbenzoxazoles in high yields.

  13. Base-promoted coupling of carbon dioxide, amines, and diaryliodonium salts: a phosgene- and metal-free route to O-aryl carbamates.

    Xiong, Wenfang; Qi, Chaorong; Peng, Youbin; Guo, Tianzuo; Zhang, Min; Jiang, Huanfeng

    2015-10-01

    A phosgene- and metal-free synthesis of O-aryl carbamates is realized through a three-component coupling of carbon dioxide, amines and diaryliodonium salts. The reaction only requires a base as the promoter, providing access to a diverse array of O-aryl carbamates in moderate to high yields with excellent chemoselectivity. PMID:26305389

  14. One-pot four-component synthesis of 2-aryl-3,3-dihaloacrylonitriles using potassium hexacyanoferrate(II) as environmentally benign cyanide source

    An efficient route to one-pot four-component reactions of aroyl chlorides, potassium hexacyanoferrate(II), triphenylphosphine and carbon tetrahalides to synthesize 2-aryl-3,3-dichloroacrylonitriles and 2-aryl-3,3-dibromoacrylonitriles was described. This protocol has advantages of use of non-toxic cyanide source, high yield and simple work-up procedure. (author)

  15. A metal-free yne-addition/1,4-aryl migration/decarboxylation cascade reaction of alkynoates with Csp(3)-H centers.

    Kong, De-Long; Cheng, Liang; Wu, Hong-Ru; Li, Yang-Xiong; Wang, Dong; Liu, Li

    2016-02-21

    A metal-free cascade reaction of aryl alkynoates with five different types of radical precursors (R-H) through an yne-addition/1,4-aryl migration/decarboxylation process was reported, which allowed facile and convenient access to functionalized vinyl products with "R" and protons located at the identical carbon of the formed double bond. PMID:26740014

  16. Synthesis and Conformational Studies of a Series of 5,17-bis-aryl-25,26,27,28-tetrapropoxycalix[4]arenes; the influence of pi-pi interactions on the molecular structure

    Larsen, Mogens; Krebs, Frederik C; Harrit, Niels; Jørgensen, Mikkel

    1999-01-01

    Four 5,17-bis-aryl-25,26,27,28-tetrapropoxycalix[4]arenes were prepared via Negishi, Suzuki and Ullman type couplings [aryl = phenyl (1), 3-bromophenyl (2), 1-naphthyl (3) and carbazol-9-yl (4)]. The influence of the aryl groups on the structure was studied by X-ray crystallography, NMR, electronic...

  17. Recyclable heterogeneous copper oxide on alumina catalyzed coupling of phenols and alcohols with aryl halides under ligand-free conditions.

    Swapna, Kokkirala; Murthy, Sabbavarapu Narayana; Jyothi, Mocharla Tarani; Nageswar, Yadavalli Venkata Durga

    2011-09-01

    An efficient alumina-supported CuO-catalyzed O-arylation of phenols and aliphatic alcohols with various aryl as well as heteroaryl halides under ligand-free conditions are reported. This protocol provides a variety of diaryl ether and bis-diaryl ether motifs by reacting different aryl/aliphatic halides with differently substituted phenols and saturated alcohols in the presence of a catalytic amount of CuO on alumina and KOH as a base at moderate temperature under nitrogen atmosphere. The described methodology is simple, straightforward and efficient to afford the cross-coupled products in high yields under ligand-free conditions. The explored catalyst is inexpensive, air-stable and recyclable up to three cycles. PMID:21695321

  18. The direct arylation of allylic sp3 C-H bonds via organic and photoredox catalysis

    Cuthbertson, James D.; MacMillan, David W. C.

    2015-03-01

    The direct functionalization of unactivated sp3 C-H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts, the establishment of general and mild strategies for the engagement of sp3 C-H bonds in C-C bond forming reactions has proved difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene and methine carbons in a catalytic manner is a priority. Although protocols for direct oxidation and amination of allylic C-H bonds (that is, C-H bonds where an adjacent carbon is involved in a C = C bond) have become widely established, the engagement of allylic substrates in C-C bond forming reactions has thus far required the use of pre-functionalized coupling partners. In particular, the direct arylation of non-functionalized allylic systems would enable access to a series of known pharmacophores (molecular features responsible for a drug's action), though a general solution to this long-standing challenge remains elusive. Here we report the use of both photoredox and organic catalysis to accomplish a mild, broadly effective direct allylic C-H arylation. This C-C bond forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants, and has been used in the direct arylation of benzylic C-H bonds.

  19. 3-Arylisoxazolyl-5-carboxylic acid and 5-(Hydroxymethyl)-3-aryl-2-isoxazoline as molecular platforms for liquid-crystalline materials

    Aline, Tavares; Paolo R., Livotto; Paulo F. B., Gonalves; Aloir A., Merlo.

    Full Text Available A sntese de uma plataforma molecular para materiais lquido-cristalinos derivados do cido 3-arilisoxazolil-5-carboxlico (1) e do 5-(hidroximetil)-3-aril-2-isoxazolina (2) descrita. Os intermedirios 1 e 2 so obtidos atravs da reao de cicloadio [3+2] 1,3-dipolar entre arilxidos de nitrila [...] s e os dipolarfilos cido acrlico e lcool allico, respectivamente. Os compostos cristais lquidos so sintetizados atravs de uma estratgia de alongamento molecular do ncleo primitivo isoxazolnico pela conexo de subunidades arilacetilnicas, as quais foram obtidas da reao de Sonogashira. Sob essas condies, sries de cristais lquidos 5a-c, 6, 7a-g e 8a-d tm sido sintetizadas com rendimentos de mdios para bons. Os compostos finais apresentam propriedades lquido-cristalinas nematognica e esmectognica. Um clculo DFT no nvel B3LYP/6-31G(d,p) tambm apresentado e alguns parmetros estruturais obtidos so analisados. Abstract in english The synthesis of the molecular platform for liquid-crystalline materials based on 3-arylisoxazolyl-5-carboxylic acid (1) and 5-(hydroxymethyl)-3-aryl-2-isoxazoline (2) is described. The key intermediates 1 and 2 are obtained by [3+2] 1,3-dipolar cycloaddition reaction between an arylnitrile oxide an [...] d an acrylic acid and allylic alcohol as the dipolarophile. The liquid crystals (LC) compounds are synthesized through a "molecular elongation strategy" from the initial isoxazolinic core by connecting the arylacetylene moiety obtained from the Sonogashira reaction. Under these conditions, the series of liquid crystals 5a-c, 6, 7a-g and 8a-d have been successfully synthesized in fair to good yields. The final compounds display nematic and smectic liquid-crystalline properties. The structural properties of the series of the liquid crystals has been studied using DFT methods at level B3LYP/6-31G(d,p). The equilibrium geometries in the gas phase are presented and analyzed.

  20. Dialkyl Ether Formation by Nickel-Catalyzed Cross-Coupling of Acetals and Aryl Iodides.

    Arendt, Kevin M; Doyle, Abigail G

    2015-08-17

    A new substrate class for nickel-catalyzed C(sp(3)) cross-coupling reactions is reported. ?-Oxy radicals generated from benzylic acetals, TMSCl, and a mild reductant can participate in chemoselective cross-coupling with aryl iodides using a 2,6-bis(N-pyrazolyl)pyridine (bpp)/Ni catalyst. The mild, base-free conditions are tolerant of a variety of functional groups on both partners, thus representing an attractive C-C bond-forming approach to dialkyl ether synthesis. Characterization of a [(bpp)NiCl] complex relevant to the proposed catalytic cycle is also described. PMID:26219537