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Sample records for n-substituted aryl compounds

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

    OpenAIRE

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

    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. Copper-catalyzed direct aryl quaternization of N-substituted imidazoles to form imidazolium salts.

    Science.gov (United States)

    Lv, Taiyong; Wang, Zhi; You, Jingsong; Lan, Jingbo; Gao, Ge

    2013-06-01

    Diaryliodonium salts are employed to directly quaternize N-substituted imidazoles by using a copper catalyst to construct aryl imidazolium salts in moderate to excellent yields. This transformation is tolerant to a broad range of functional groups and provides a straightforward, efficient, and versatile route to synthesize aryl imidazolium as well as triazolium salts, especially the unsymmetric version. PMID:23641785

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

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    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. A study on applications of N-substituted main-chain NHC-palladium polymers as recyclable self-supported catalysts for the Suzuki-Miyaura coupling of aryl chlorides in water.

    Science.gov (United States)

    Karimi, Babak; Akhavan, Pari Fadavi

    2011-07-01

    The preparation and characterization of a number of main-chain organometallic polymers (NHC-Pd MCOP) with different N-alkyl substituted groups such as benzyl (3a), n-hexyl (3b), and n-dodecyl (3c) are described. Among these polymers, 3c bearing the more lipophilic group n-dodecyl was found to be a more reactive and recoverable catalytic system in the Suzuki-Miyaura cross-coupling reaction of chloroarenes, including both deactivated and hindered aryl chlorides with different types of arylboronic acids under aqueous conditions. While the catalysts seem to be highly recyclable, on the contrary, we have provided much compelling evidence, such as kinetic monitoring, poisoning experiments, and average molecular weight determination before and after catalysis, that shows that the described organometallic polymers might be indeed the source of production of active soluble Pd species in the form of either Pd nanoparticles or fragmented NHC-Pd complexes. Our studies showed that in order to assess whether the catalysts are functioning in a heterogeneous pathway or they are simply a source of production of active Pd species, it is crucial to devise a suitable and highly efficient poison that could capture essentially soluble catalytic species. In this regard, we interestingly found that among a variety of well-known catalyst poisons such as Hg(0), SBA-15-PrSH, and cross-linked poly(4-vinylpyridine) (PVP), only PVP could efficiently quench catalysis, thus providing clear evidence of the formation soluble Pd species in our protocol. In addition, several experiments such as bright-field microscopy, dynamic light scattering (DLS) of the reaction mixture, and kinetic monitoring of the reaction at an early stage confirm not only that the described organometallic polymers could be a source of production of trace amounts of Pd nanoparticles but the capsular structures of these lipophilic polymers in water provides a means of entrapment of nanoclusters in a hydrophobic region, thus accelerating the reaction in pure water in the absence of any co-organic solvent. PMID:21648445

  5. A structure-activity study with aryl acylamidases.

    Science.gov (United States)

    Villarreal, D T; Turco, R F; Konopka, A

    1994-11-01

    We examined the relationship between chemical structure and biodegradability of acylanilide herbicides by using a set of model compounds. Four bacterial isolates (one gram-negative and three gram-positive) that grew on acetanilide were used. These soil isolates cleaved the amide bond of acetanilide via an aryl acylamidase reaction, producing aniline and the organic acid acetate. A series of acetanilide analogs with alkyl substitutions on the nitrogen atom or the aromatic ring were tested for their ability to induce aryl acylamidase activity and act as substrates for the enzyme. The substrate range, in general, was limited to those analogs not disubstituted in the ortho position of the benzene ring or which did not contain an alkyl group on the nitrogen atom. These same N-substituted compounds did not induce enzyme activity either, whereas the ortho-substituted compounds could in some cases. PMID:16349428

  6. Possibility of mesophase formation in some model compounds based on the N-aryl benzamide group

    International Nuclear Information System (INIS)

    Five series of N-aryl-4-alkoxybenzamides [RO-C6H4-CONH-C6H4-X] were prepared where the terminal alkoxy group (RO) possesses a number of carbon atoms (n) that varies between 8, 10, 12, 14, or 18 carbons, while the other terminal substituent (X) alternatively changes from CH3O, CH3, H, Cl, and NO2. The terminal group X was introduced once in position 4- with respect to the anilide C=O group, furnishing, as expected, linear molecules, and others in the 2- (or 3-) positions aiming to induce some steric hindrance to the linear association of the rod-shaped molecules, specially in the solid phase. Further replacement of the anilide-H atom with a methyl (CH3) group was performed into the unsubstituted derivatives (X=H) in order to disrupt any unfavourable hydrogen bonding between any two neighbouring molecules. Compounds prepared were characterized by elemental analyses, infrared, and 1H NMR spectra, and their phase behaviour investigated by differential scanning calorimetry and polarized-light microscopy. The results were discussed in terms of mesomeric, steric, polarity, and polarizability effects. Independent of the polarity or position of the substituent X, all compounds prepared were found to be non-mesomorphic. The N-methyl derivative (that excludes the possibility of hydrogen-bond formation) was also found to be non-mesomorphic. In all five series of compounds, their tenIn all five series of compounds, their tendency to form a mesophase (smectic or nematic) was estimated from their binary phase diagrams with either of the smectogenic compound, 4-n-C16H33O-C6H4-COO-C6H4-OOC-C6H4-CN, or the nematogenic compound, 4-n-C16H33O-C6H4-COO-C6H4-OOC-C6H4-CH3. Dipole moment calculations for the core structure (benzanilide) revealed that such a group of compounds exists in a non-linear, non-planar conformation

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

    International Nuclear Information System (INIS)

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

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    A. Sivakumar

    2012-08-01

    Full Text Available A series of Schiff base of 2,2'-(naphthalene-2,7-diylbis(oxybis(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(oxydiacetohydrazide (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 screened for their in vitro antibacterial activity.DOI: http://dx.doi.org/10.4314/bcse.v26i2.9

  9. Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans

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    Hans Steenackers

    2014-10-01

    Full Text Available Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number of tumor cell lines (L1210, CEM and HeLa. A subset of monosubstituted 5-aryl-2-aminoimidazoles showed a moderate safety window, with therapeutic indices (TIs ranging between 3 and 20. Whereas introduction of a (cyclo-alkyl chain at the N1-position strongly reduced the TI, introduction of a (cyclo-alkyl chain or a triazole moiety at the 2N-position increased the TI up to 370. Since a promising application of preventive anti-biofilm agents is their use in anti-biofilm coatings for orthopedic implants, their effects on cell viability and functional behavior of human osteoblasts and bone marrow derived mesenchymal stem cells were tested. The 2N-substituted 5-aryl-2-aminoimidazoles consistently showed the lowest toxicity and allowed survival of the bone cells for up to 4 weeks. Moreover they did not negatively affect the osteogenic differentiation potential of the bone cells. Finally, we examined the effect of the compounds on the survival of Caenorhabditis elegans, which confirmed the higher safety window of 2N-substituted 5-aryl-2-aminoimidazoles.

  10. Synthesis and oxidation by xanthine oxidase from Arthrobacter M-4 of 6-aryl-4(3H)-pteridinones and related compounds.

    OpenAIRE

    Meester, J. W. G.

    1987-01-01

    In this thesis xanthine oxidase from Arthrobacter M-4 in the form of a cell-free extract or as immobilized cells has been studied with regard to its application In preparative organic chemistry. The enzyme has a broad substrate specificity towards azaheterocycles as purines and pteridines.The unequivocal preparation of 6-aryl-4(3H)-pteridinones and 7-aryl-4(3H)- pteridinones with different substituents at the para position of the phenyl group is described. The oxidation of these compounds by ...

  11. A Novel Compound, NK150460, Exhibits Selective Antitumor Activity against Breast Cancer Cell Lines through Activation of Aryl Hydrocarbon Receptor.

    Science.gov (United States)

    Fukasawa, Kazuteru; Kagaya, Shigehide; Maruyama, Sakiko; Kuroiwa, Shunsuke; Masuda, Kuniko; Kameyama, Yoshio; Satoh, Yoshitaka; Akatsu, Yuichi; Tomura, Arihiro; Nishikawa, Kiyohiro; Horie, Shigeo; Ichikawa, Yuh-Ichiro

    2015-02-01

    Antiestrogen agents are commonly used to treat patients with estrogen receptor (ER)-positive breast cancer. Tamoxifen has been the mainstay of endocrine treatment for patients with early and advanced breast cancer for many years. Following tamoxifen treatment failure, however, there are still limited options for subsequent hormonal therapy. We discovered a novel compound, NK150460, that inhibits 17?-estradiol (E2)-dependent transcription without affecting binding of E2 to ER. Against our expectations, NK150460 inhibited growth of not only most ER-positive, but also some ER-negative breast cancer cell lines, while never inhibiting growth of non-breast cancer cell lines. Cell-based screening using a random shRNA library, identified aryl hydrocarbon receptor nuclear translocator (ARNT) as a key gene involved in NK150460's antitumor mechanism. siRNAs against not only ARNT but also its counterpart aryl hydrocarbon receptor (AhR) and their target protein, CYP1A1, dramatically abrogated NK150460's growth-inhibitory activity. This suggests that the molecular cascade of AhR/ARNT plays an essential role in NK150460's antitumor mechanism. Expression of ER? was decreased by NK150460 treatment, and this was inhibited by an AhR antagonist. Unlike two other AhR agonists now undergoing clinical developmental stage, NK150460 did not induce histone H2AX phosphorylation or p53 expression, suggesting that it did not induce a DNA damage response in treated cells. Cell lines expressing epithelial markers were more sensitive to NK150460 than mesenchymal marker-expressing cells. These data indicate that NK150460 is a novel AhR agonist with selective antitumor activity against breast cancer cell lines, and its features differ from those of the other two AhR agonists. Mol Cancer Ther; 14(2); 343-54. ©2014 AACR. PMID:25522763

  12. Synthesis and characterization of some N-substituted amides of salicylic acid

    OpenAIRE

    Lupea Xenia Alfa; Padure Mirabela

    2003-01-01

    The synthesis of some N-substituted aromatic amides in the salicylic acid series was achieved, by direct reaction between primary amines and salicylic acid in inert organic solvent, in the presence of PCl3. The compounds that were obtained, partially not described in literature, were characterized by chemical-physical methods.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  14. Structural investigations on N'-substituted N-acylguanidines - Intermolecular interactions with solvents, anions and receptors

    OpenAIRE

    Kleinmaier, Roland

    2011-01-01

    Acylguanidines are an abundant class of compounds with various applications in organic and pharmaceutical chemistry. Within the subgroup of N’-substituted and especially monoalkylated N-acylguanidines, highly potent and selective ligands for G protein coupled receptors have been identified in recent years. In the field of molecular recognition, acylguanidines are valued for their ability to form strong fork-like hydrogen bond (H-bond) interactions with carboxylate anions. Although their bas...

  15. 40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

    Science.gov (United States)

    2010-07-01

    ...2-propenyl)-N-(substituted phenyl) acetamide. 721.275 Section 721.275 ...2-propenyl)-N-(substituted phenyl) acetamide. (a) Chemical substances and significant...2-propenyl)-N -(substituted phenyl) acetamide (P-83-1085) is subject to...

  16. Indium(III)-catalyzed synthesis of N-substituted pyrroles under solvent-free conditions

    Scientific Electronic Library Online (English)

    Jiu-Xi, Chen; Miao-Chang, Liu; Xiao-Liang, Yang; Jin-Chang, Ding; Hua-Yue, Wu.

    Full Text Available SciELO Brazil | Language: English Abstract in portuguese Vários pirróis N-substituídos foram sintetizados pela reação de ?-dicetonas (R¹C(O)CH2CH2C(O)R²: R¹, R² = Me, Ph) com aminas (RNH2: R = Alkyl, Aryl, TsNH) ou diaminas (1,6-diaminohexano and 1,2-diaminoetano) na presença de tribrometo de índio, tricloreto de índio ou trifluorometanossulfonato de índi [...] o a temperatura ambiente e sem solventes. O protocolo envolve operações simples e os produtos são isolados em excelentes rendimentos (81-98%). Abstract in english A variety of N-substituted pyrroles have been synthesized by reacting ?-diketones (R¹C(O)CH2CH2C(O)R²: R¹, R² = Me, Ph) with amines (RNH2: R=Alkyl, Aryl, TsNH) or diamines (1,6-diaminohexane and 1,2-diaminoethane) in the presence of indium tribromide, indium trichloride or indium trifluoromethanesul [...] fonate at room temperature under solvent-free conditions. The experiment protocol features simple operations, and the products are isolated in high to excellent yields (81-98%).

  17. SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL SCREENING OF VARIOUS N-SUBSTITUTED DERIVATIVES OF SULFONAMIDES

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    AZIZ-UR-REHMAN, WAJEEHA TANVEER, MUHAMMAD ATHAR ABBASI, SUMBAL AFROZ, KHALID MOHAMMED KHAN, MUHAMMAD ASHRAF, AND IFTIKHAR AFZAL

    2011-12-01

    Full Text Available In the present study, a series of N-substituted sulfonamides have been synthesized. The reaction ofbenzene sulfonyl chloride (1 with O-anisidine (2 yielded N-(2-methoxyphenyl benzenesulfonamide (3, which onbromination with bromine in the presence of acetic acid gave N-(4,5-dibromo-2-methoxyphenylbenzenesulfonamide(6. The two products (3 and (6 further on treatment with alkyl halides/acyl halide in the presence of sodium hydrideyielded thirteen different N-substituted sulfonamides. The compounds were characterized by IR, EIMS and 1H-NMRand screened against acetyl cholinesterase, butyryl cholinesterase and lipoxygenase enzymes. The results revealedthat N-butyl-N-(4, 5-dibromo-2-methoxyphenylbenzene sulfonamide (6d and N-pentyl-N-(4,5-dibromo-2-methoxyphenylbenzenesulfonamide (6e exhibited good inhibitory potential against lipoxygenase.

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

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    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.

  19. On the existence of the chair conformation in six-membered ring phosphates bearing an aryl group axially oriented at the C4 position: cyclic nucleotides as model compounds for cyclic phosph(on)ate and phosphoramide prodrugs.

    Science.gov (United States)

    Quintero, Leticia; Sánchez-Vazquez, Mario; Cruz-Gregorio, Silvano; Sartillo-Piscil, Fernando

    2010-09-01

    A series of cyclic nucleotide analogues to HepDirect prodrugs were prepared by a three-component reaction of protected thymine, phosphoryl chloride, and 5-aryl-alpha-D-xylofuranoses derivatives. One of the cyclic nucleotides showed NMR data that suggest a predominant twisted conformation; however, in spite of having an aryl group at the C4 position within the crystal lattice, the cyclic nucleotide had a chair conformation with the aryl group axially oriented. By analyzing the unprecedented X-ray structure, it was observed that the oxygen atom from the phoshoryl group (P=O) is found in close proximity to the o-hydrogen atom of the aryl group (2.51 A), suggesting thus an attractive nonbonding electrostatic interaction, which might be the driving force that overcomes the steric diaxial interactions imposed by the aryl group. Theoretical studies (NBO) for two model compounds showed that there are indeed interactions between filled (donor) Lewis-type NBOs and empty (acceptor) non-Lewis NBOs corresponding to the nO-->sigma*(C-H) interaction. Additionally, conversion of a diastereomeric mixture of cyclic nucleotides into the more stable diastereomeric cyclic nucleotide was observed and explained by spontaneous isomerization in the phosphorinane ring. This finding supports the recently established hypothesis for the mode of action of prodrug cleavage, for which the anomeric effect plays an important role. PMID:20698556

  20. A cascade synthesis of aminohydantoins using in situ-generated N-substituted isocyanates.

    Science.gov (United States)

    Vincent-Rocan, Jean-François; Clavette, Christian; Leckett, Kyle; Beauchemin, André M

    2015-03-01

    Nitrogen-substituted isocyanates are rarely utilized but powerful building blocks for the development of cascade reactions in heterocyclic synthesis. These reactive amphoteric intermediates can be accessed in situ via an equilibrium that allows controlled reactivity in the presence of bifunctional partners such as ?-amino esters. A cascade reaction has been carried out that forms 3-aminohydantoin derivatives using simple phenoxycarbonyl derivatives of hydrazides and hydrazones as precursors of N-substituted-isocyanates. This method allows rapid assembly of complex aminohydantoin derivatives, including analogues of medicinally-relevant compounds, using simple reactants. PMID:25631378

  1. Fluorination of aromatic compounds by cleavage of aryl-tin bonds with F-18 F/sub 2/ and CH/sub 3/COOF

    International Nuclear Information System (INIS)

    Direct fluorination of aromatic nuclei is difficult since the reaction is usually accompanied by unselective, partial, or total replacement of hydrogen. By attaching the tri-n-butyltin moiety to one position of the ring one can achieve an enhanced reactivity and site selectivity toward electrophilic fluorination. The intent of this study was to demonstrate the utility of the fluorodestannylation reaction for fluorine labelling of aromatic compounds and to compare F/sub 2/ and acetyl hypofluorite as the fluorinating agents. Thus, eight stannylated aromatic compounds (1-8) were synthesized via lithium halogen exchange of the bromo precursor and subsequent transmetallation using tri-n-butyltin chloride. The stannylated substrates were treated with F-18 F/sub 2/ and -780C and CH/sub 3/COOF at room temperature. Both reagents gave good yields of labelled aryl fluorides. Overall, acetyl hypofluorite gave more consistent yields (?70%), while F/sub 2/ gave more variable yields (54-95%). This method is currently being extended to label more complex systems such as L-Dopa with F-18 for brain studies with positron emission tomography. The authors have successfully stannylated Dopa on the ring and fluorination studies of this substrate are underway

  2. Assays of dioxins and dioxin-like compounds in actually contaminated soils using transgenic tobacco plants carrying a recombinant mouse aryl hydrocarbon receptor-mediated ?-glucuronidase reporter gene expression system

    OpenAIRE

    Inui, Hideyuki; Gion, Keiko; Utani, Yasushi; Wakai, Taketo; Kodama, Susumu; Eun, Heesoo; Kim, Yun-seok; Ohkawa, Hideo

    2012-01-01

    The transgenic tobacco plant XD4V-26 carrying the recombinant mouse aryl hydrocarbon receptor XD4V-mediated ?-glucuronidase (GUS) reporter gene expression system was used for assay of dioxins and dioxin-like compounds consisting of polychlorodibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls (Co-PCBs) in actually contaminated soils. The transgenic tobacco plant XD4V-26 showed a significant dose-dependent induced GUS activity when cultured on MS medium co...

  3. 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

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    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.

  4. Synthesis of N-substituted N-nitrosohydroxylamines as inhibitors of mushroom tyrosinase.

    Science.gov (United States)

    Shiino, M; Watanabe, Y; Umezawa, K

    2001-05-01

    A series of N-substituted N-nitrosohydroxylamines including six new compounds were synthesized and examined for inhibition of mushroom tyrosinase. Corresponding hydroxylamines were reacted with n-butyl nitrite to give substituted nitrosohydroxylamines as their ammonium salt. The N-substituted hydroxylamines were prepared from the primary amines via the oxaziridine, or from the carbonyl compounds via the oxime. Most of the nitrosohydroxylamines tested inhibited mushroom tyrosinase. Among them, N-cyclopentyl-N-nitrosohydroxylamine exhibited the most potent activity (IC(50)=0.6 microM), as powerful as that of tropolone, one of the most powerful inhibitors. As removal of nitroso or hydroxyl moiety, the enzyme inhibitory activity was completely diminished. Both N-nitroso group and N-hydroxy group were suggested to be essential for the activity, probably by interacting with the copper ion at the active site of the enzyme. Lineweaver-Burk plotting showed that cupferron was a competitive inhibitor but that N-cyclopentyl-N-nitrosohydroxylamine was not. PMID:11377181

  5. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    Science.gov (United States)

    2010-07-01

    ...2-Chloro-N-methyl-N-substituted acetamide (generic name). 721.225 Section...2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical...2-chloro-N -methyl-N -substituted acetamide (PMN P-84-393) is subject...

  6. Regiospecific synthesis of mono-N-substituted indolopyrrolocarbazoles.

    Science.gov (United States)

    Fröhner, Wolfgang; Monse, Barbara; Braxmeier, Tobias M; Casiraghi, Laura; Sahagún, Heidi; Seneci, Pierfausto

    2005-10-13

    [reactions: see text] Two complementary and efficient strategies have been developed for the regiospecific synthesis of unsymmetrical indolopyrrolocarbazoles (IPCs) mono-N-substituted with a pentacycle. A halogen in position 2 of the intermediate bisindolylmaleimides 3a-e allows a selective Mitsunobu coupling by exploiting the increased acidity of the 2-chloro-substituted indole nitrogen. It also promotes an easier cyclization of bisindolylmaleimides 4a-e and 7b-e to IPCs. Alkylation of the 2-unsubstituted indole-3-carboxamides 2a,b and further processing to the corresponding IPCs gives access to the opposite regioisomers. PMID:16209482

  7. Synthesis and characterization of N-substituted bis(2-mercaptoethyl)amino ligands and their technetium complexes

    International Nuclear Information System (INIS)

    A present need in the field of technetium radiopharmacy is the isolation of a neutral mono-chelated technetium complex (one ligand to one technetium). If such a moiety can be attached to a receptor specific compound without hindering the specificity of the compound, a new class of site specific imaging agents may be formulated. Recently a series of bidentate N-substituted 2-mercaptoethylamines were synthesized and complexed with technetium-99m and -99. The resulting complexes were found to be neutral. Their lipophilicity was dependent on the size and structure of group on the amine nitrogen. Also these complexes were discovered to contain two ligands per technetium

  8. Modern Arylation Methods

    CERN Document Server

    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

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

    International Nuclear Information System (INIS)

    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.

  10. ?-Alkyl and ?-aryl complexes

    International Nuclear Information System (INIS)

    Methods of preparation, solubility, reactivity, as well as molecular and crystal structure of ?-alkyl and ?-aryl complexes of rare earths of different composition are described. Di- and trisubstituted alkyl (aryl)lanthanides, their halogen derivatives of RLnHal type, afe-complexes, complexes of Cp2LnR type and ilide derivatives are considered in particular. 173 refs.; 17 figs.; 12 tabs

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

    Directory of Open Access Journals (Sweden)

    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

  12. Synthesis, characterization and biological screening of N-substituted derivatives of 5-benzyl-1,3,4-oxadiazole-2yl-2"-sulfanyl acetamide.

    Science.gov (United States)

    Siddiqui, Sabahat Zahra; Rehman, Azizur; Abbasi, Muhammad Athar; Abbas, Nadia; Khan, Khalid Mohammed; Ashraf, Muhammad; Ejaz, Syeda Abida

    2013-05-01

    A series of new N-substituted derivatives of 5-benzyl-1, 3, 4-oxadiazole-2yl-2"-sulfanyl acetamide (6a-n) were synthesized in three phases. The first phase involved the sequentially converting phenyl acetic acid into ester, hydrazide and finally cyclized in the presence of CS2 to afford 5-benzyl-1, 3, 4-oxadiazole-2-thiol. In the second phase N-substituted-2-bromoacetamides were prepared by reacting substituted amines with bromoacetyl bromide in basic media. In the third phase, 5-benzyl-1,3,4-oxadiazole-2-thiol was stirred with N-substituted-2-bromoacetamides in the presence of N,N-dimethyl formamide (DMF) and sodium hydride (NaH) to get the target compounds. Spectral techniques were used to confirm the structures of synthesized compounds. Synthesized compounds were screened against butyrylcho linesterase (BChE), acetylcholinesterase (AChE), and lipoxygenase enzymes (LOX) and were found to be relatively more active against acetylcholinesterase. PMID:23625417

  13. Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-?-carbolines.

    Science.gov (United States)

    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-?-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 ?M, respectively. Analogs 9b and 11h were also effective against axenic amastigotes with IC50 values of 62.8 and 87.6 ?M, 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 ?M. 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 ?M, 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

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

    Directory of Open Access Journals (Sweden)

    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 structure–activity 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.

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

    OpenAIRE

    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...

  16. SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL SCREENING OF VARIOUS N-SUBSTITUTED DERIVATIVES OF SULFONAMIDES

    OpenAIRE

    Aziz-ur-rehman, Wajeeha Tanveer

    2011-01-01

    In the present study, a series of N-substituted sulfonamides have been synthesized. The reaction ofbenzene sulfonyl chloride (1) with O-anisidine (2) yielded N-(2-methoxyphenyl) benzenesulfonamide (3), which onbromination with bromine in the presence of acetic acid gave N-(4,5-dibromo-2-methoxyphenyl)benzenesulfonamide(6). The two products (3) and (6) further on treatment with alkyl halides/acyl halide in the presence of sodium hydrideyielded thirteen different N-substituted sulfonamides. The...

  17. Palladium-catalyzed direct arylation of phenols with aryl iodides.

    Science.gov (United States)

    Long, Rongrong; Yan, Xufei; Wu, Zhiqing; Li, Zhengkai; Xiang, Haifeng; Zhou, Xiangge

    2015-03-11

    An efficient protocol of palladium-catalyzed direct para-arylation of unfunctionalized phenols with aryl iodides under mild conditions was reported. A variety of substrates were applied in this reaction with yields up to 87%. PMID:25686911

  18. Rhodium-Catalyzed Highly Regioselective C-H Arylation of Imidazo[1,2-a]pyridines with Aryl Halides and Triflates

    International Nuclear Information System (INIS)

    A convenient Rh-catalyzed C-H arylation of imidazo[1,2-a]pyridines with a variety of aryl halides or triflates has been reported. This process afforded a range of biaryl compounds in excellent yields and showed high activity and broad scope

  19. Study of germathiazolidines and germylated dithiocetals derived from N-substituted cysteamine and methylcysteamine: synthesis and radioprotective activity

    International Nuclear Information System (INIS)

    Synthesis and pharmacological studies (toxicity, radioprotective activity) of new N-substituted germathiazolidines and germylated dithioacetals prepared from N-substituted cysteamine and methylcysteamine by an acetyl group or a partial amino acid are described. A notable decrease in the toxicity and a rather important increase in the radioprotective activity of these new organometallic molecules compared to N-substituted cysteamine and methylcysteamine have been observed

  20. Synthesis and antimicrobial profile of N-substituted imidazolium oximes and their monoquaternary salts against multidrug resistant bacteria.

    Science.gov (United States)

    Odžak, Renata; Sko?ibuši?, Mirjana; Maravi?, Ana

    2013-12-01

    Two different series of N-substituted imidazolium oximes and their monoquaternary salts were synthesized and biologically tested with respect to their ability to inhibit growth a diverse panel of antibiotic susceptible Gram-positive and antibiotic resistant Gram-negative bacteria as well fungal strains. The newly synthesized compounds were analyzed by spectral studies to confirm their structure. The preliminary results showed that all compounds tested possess promising antimicrobial potential against both susceptible Gram-positive and antibiotic resistant Gram-negative isolates, exhibiting a wide range of MIC values from 0.14 to 100.0 ?g/mL. The structure-activity relationship demonstrates that the p-methylphenyl and p-fluorophenyl groups in monoquaternary salts 6 and 7 attached directly to the imidazolium ring could be essential for observed remarkable inhibitory profiles against clinically important pathogens Pseudomonas aeruginosa (MIC=0.14 ?g/mL) and Klebsiella pneumoniae (MIC=1.56 ?g/mL). Furthermore, the broth microdilution assay was then used to investigate the antiresistance efficacy of compound 7 against fourteen extended-spectrum ?-lactamase (ESBL)-producing strains in comparison to eight clinically relevant antibiotics. Compound 7 exhibited a remarkable antiresistance profiles ranging between 0.39 and 12.50 ?g/mL against all of ESBL-producing strains, which leads to the suggestion that may be interesting candidate for development of new antimicrobials to combat multidrug resistant Gram-negative bacteria. PMID:24126094

  1. The effect of N-substituted alkyl groups on the anticonvulsant activities ofN-Cbz-alpha-amino-N-alkylsuccinimides.

    Science.gov (United States)

    Lee, J; Son, K; Jung, K; Choi, J; Park, M

    1997-02-01

    For the purpose of defining the effects of theN-substituted alkyl groups on the anticonvulsant activities ofN-Cbz-alpha-aminosuccinimides, various (R)-and(S)-N-alkyl substitutedN-Cbz-alpha-aminosuccinimides (1 and2) were prepared from the corresponding (R)-and(S)-N-Cbz-aspartic acid by using known reaction and were evaluated the anticonvulsant activies in the MES and PTZ tests, including their neurotoxicities. The most active compound in the MES test was(R)-N-Cbz-alpha-amino-N-methylsuccinimide (1b) (ED(50)=52.5 mg/kg, Pl-3.2). And in case of the PTZ test,(R)-N-Cbz-alpha-amino-N-ethylsuccinimide (1c) was the most active compound (ED(50)=32.5 mg/kg, Pl=3.1). The order of anticonvulsant activities of these compounds against the MES test, as judged from the ED(50) values for theR series (1), wasN-methyl >N-isobutyl > non-substituted >N-ethyl,N-allyl >N-benzyl compound; for theS series (2)N-methyl >N-allyl > non-substituted >N-isobutyl >N-ethyl >N-benzyl compound. The anticonvulsant activities in the PTZ tests of these compounds exhibited somewhat different pattern; for theR series (1)N-ethyl >N-methyl >N-isobutyl> non-substituted >N-allyl >N-benzyl compound in order of decreasing activity; forS series (2)N-ethyl >N-allyl, non-substituted >N-isobutyl >N-methyl >N-benzyl compound in order of decreasing activity. PMID:18975212

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

    DEFF Research Database (Denmark)

    Jensen, Thomas; Pedersen, Henrik

    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 single indole regioisomer, which can be functionalized in situ by N-arylation (see scheme).

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Nickel-catalyzed decarboxylative cross-coupling of perfluorobenzoates with aryl halides and sulfonates.

    Science.gov (United States)

    Sardzinski, Logan W; Wertjes, William C; Schnaith, Abigail M; Kalyani, Dipannita

    2015-03-01

    A Ni-catalyzed method for the coupling of perfluorobenzoates with aryl halides and pseudohalides is described. Aryl iodides, bromides, chlorides, triflates, and tosylates participate in these transformations to afford the products in good yields. Penta-, tetra-, and trifluorinated biaryl compounds are obtained using these newly developed Ni-catalyzed decarboxylative cross-coupling reactions. PMID:25700128

  5. Synthesis of unsymmetrical imidazolium salts by direct quaternization of N-substituted imidazoles using arylboronic acids.

    Science.gov (United States)

    Li, Shiqing; Yang, Fan; Lv, Taiyong; Lan, Jingbo; Gao, Ge; You, Jingsong

    2014-04-18

    Imidazolium salts were conveniently prepared by direct aryl quaternization using arylboronic acids. This process features the tolerance of a broad range of functional groups and excellent chemoselectivity, and is especially effective for the synthesis of unsymmetrical imidazolium salts. PMID:24599288

  6. Synthesis and Caco-2 cell permeability of N-substituted anthranilamide esters as ADP inhibitor in platelets.

    Science.gov (United States)

    Kim, Sohee; Shin, Beom Soo; Ma, Eunsook

    2014-10-18

    Twelve N-substituted anthranilamide esters (1-5, 8, 9, 12, 13, and 15-17) were synthesized and evaluated for their ability to inhibit the in vitro aggregation by washed human platelets induced by adenosine 5'-diphosphate (10 ?M). The antiplatelet activity of DL-n-butyl 5-hydroxy-N-(2-phenoxypropionyl)anthranilate (9, IC50 = 10.5 ?M) was most active among the tested compounds and ethyl ester 8 (IC50 = 11.2 ?M) showed the second most activity. DL-Ethyl and DL-n-butyl 5-(p-toluenesulfonyloxy)-N-(2-phenoxypropionyl)anthranilate (12, IC50 = 13.1 ?M and 13, IC50 = 14.0 ?M), DL-methyl N-(2-phenoxybutyryl)anthranilate (2, IC50 = 12.7 ?M), DL-N-(2-phenoxypropionyl)anthranilic acid (5, IC50 = 13.7 ?M) displayed lower antiplatelet activity than 8 and 9. Compound 5 was more active than methyl ester prodrug 1. n-Butyl 5-hydroxy-N-(4'-acetoxybenzoyl)anthranilate (15, IC50 = 28.3 ?M) showed moderate activity. Compounds 1 (IC50 = 42.8 ?M), 4 (IC50 = 56.7 ?M), 16 (IC50 = 51.0 ?M), and 17 (IC50 = 49.8 ?M) exhibited low antiplatelet activity. Methyl N-phenoxyacetylanthranilate (3, IC50 = 78.0 ?M) showed the lowest antiplatelet activity. The compounds with branched alkyl chain (2 and 5) were more active than compounds with straight chain (3 and 4). The apparent permeability coefficient (Papp, cm/s) values of compounds 2 and 9 were determined as 45.34 ± 4.67 and 33.17 ± 5.15 × 10(-6) cm/s by Caco-2 cell permeability assay. PMID:25325926

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

    International Nuclear Information System (INIS)

    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 ?M 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 ?M. At 200 ?M, 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 ?M. 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 ?M. Intracellular glutathione (GSH) content and mitochondrial MTT reduc 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 ?M 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

  8. Synthesis of aryl phosphates based on pyrimidine and triazine scaffolds.

    Science.gov (United States)

    Courme, Caroline; Gresh, Nohad; Vidal, Michel; Lenoir, Christine; Garbay, Christiane; Florent, Jean-Claude; Bertounesque, Emmanuel

    2010-01-01

    The syntheses of the triazinyl-based bis-aryl phosphates 2 and 3, and of the aminopyrimidyl-based aryl phosphate 4 are described. Each compound contains a diaryl ether-phosphate structural motif. The synthetic route to bis-aryl phosphates 2 and 3 consisted in two nucleophilic substitution reactions with amines from cyanuric chloride, followed by a Suzuki coupling with the resulting 2,4-diamino-6-chloro-1,3,5-triazine derivative 12 to introduce the diaryl ether functionality. Aryl phosphate 4 was obtained via condensation of aryl guanidine 34 with aryloxyphenyl butenone 31. These de novo-designed aryl phosphates were evaluated as potential inhibitors of the Grb2-SH2 domain using an ELISA assay. The water-soluble sodium salt 26 of 3 gave an IC(50) value in the high micromolar range. Molecular modeling studies were subsequently performed upon modifying the 1,3,5-trisubstituted triazine scaffold of 3. Non-phosphate derivatives encompassing cyclopropane, pyrrole, keto-acid, and IZD fragments were thus step-wise designed and their Grb2-SH2 complexes were modeled by molecular dynamics. Some derivatives gave rise to an enriched pattern of H-bonds and cation-pi interactions with Grb2-SH2. PMID:19906464

  9. Copper Mediated Fluorination of Aryl Iodides

    OpenAIRE

    Fier, Patrick S.; Hartwig, John F.

    2012-01-01

    The synthesis of aryl fluorides has been a topic of considerable interest because of the importance of aryl fluorides in pharmaceuticals, agrochemicals and materials. The stability, reactivity and biological properties of aryl fluorides can be distinct from those of the corresponding arenes. Methods for the synthesis of aryl fluorides, however, are limited. We report the conversion of a diverse set of aryl iodides to the corresponding aryl fluorides. This reaction occurs with a cationic coppe...

  10. Synthesis and acetylcholinesterase (AChE inhibitory activity of some N -substituted-5-chloro-2(3 H - benzoxazolone derivatives

    Directory of Open Access Journals (Sweden)

    Zeynep Soyer

    2013-01-01

    Full Text Available Alzheimer’s disease is a progressive neurodegenerative disorder of the central nervous system. Acetylcholinesterase inhibition is one of the proposed mechanisms for treatment of Alzheimer’s disease. Currently, acetylcholinesterase inhibitors such as tacrine,donepezil, rivastigmine and galantamine are applied in different stages of Alzheimer’s disease teratment. In recent years, various heterocyclic systems have been used as a skeletonto discover new acetylcholinesterase inhibitors. On the other hand, it is known that the benzoxazolone heterocyclic structure exhibited a wide range of biological activities. In this study, a seriesN-substituted-5-chloro-2(3H-benzoxazolone derivatives were synthesized and evaluated their acetylcholinesterase inhibitory activity. These compounds were synthesized by Mannich reaction of 5-chloro-2(3H-benzoxazolone with the appropriated amines.The acetylcholinesterase inhibitory activity of the title compounds was determined by colorimetric Ellman’s method. The preliminary screening results indicated that 5-chloro-2-(3H-benzoxazolone scaffold demonstrated different inhibition range againstacetylcholinesterase enzyme depending on the structural differences

  11. Aryl substitution of pentacenes

    OpenAIRE

    Waterloo, Andreas R.; Sale, Anna-chiara; Lehnherr, Dan; Hampel, Frank; Tykwinski, Rik R.

    2014-01-01

    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 UV–vis 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 spec...

  12. DFT Study of Oxygen Reduction Reaction on N-substituted Carbon Electrodes. Adsorption

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Hisayoshi; Tomoya, Nakzono; Miyazaki, Soichi; Miura, Toshiko; Takeuchi, Nobuyuki [Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan); Yamabe, Tokio, E-mail: kobayashi@chem.kit.ac.jp [Nagasaki Institute of Applied Science, 536, Amibacho, Nagasaki 851-0123 (Japan)

    2011-05-15

    Carbon alloys attract attention as metal-free cathode catalysts. Mechanisms of oxygen reduction reactions are investigated using the DFT calculations and molecular models such as N-substituted coronene, circum pyrene, and corannulene. The overall oxygen reduction reaction (ORR) is decomposed into five elementary reactions. Adsorption of O{sub 2} is important as the first step of reduction, and it depends strongly on the spin density on C atoms, introduced by the N atom. Secondly the peripheral C atoms have an advantage due to the rehybridization freedom to the sp{sup 3} configuration. Based on the reversible electrode potential (REP) for each elementary reaction, the overpotential is expected for the first reduction of O{sub 2} to OOH and the final reduction of OH to H{sup 2}O. These features indicate that N-substituted carbon electrode resembles Pt electrode compared to other less active metals, such as Au.

  13. Synthesis and pharmacological evaluation of N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide as cyclooxygenase inhibitors.

    Science.gov (United States)

    Rambabu, D; Mulakayala, Naveen; Ismail; Kumar, K Ravi; Kumar, G Pavan; Mulakayala, Chaitanya; Kumar, Chitta Suresh; Kalle, Arunasree M; Rao, M V Basaveswara; Oruganti, Srinivas; Pal, Manojit

    2012-11-01

    A series of novel N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide derivatives were synthesized via converting the readily available 4-hydroxy coumarin to the corresponding ethyl 2-(2-oxo-2H-chromen-4-yloxy)propanoate followed by hydrolysis and then reacting with different substituted amines. The molecular structures of two representative compounds, that is, 3 and 5l were confirmed by single crystal X-ray diffraction study. All the compounds synthesized were evaluated for their cyclooxygenase (COX) inhibiting properties in vitro. The compound 5i showed balanced selectivity towards COX-2 over COX-1 inhibition and good docking scores when docked into the COX-2 protein. PMID:23010270

  14. Direct N9-arylation of purines with aryl halides

    DEFF Research Database (Denmark)

    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.

  15. Complexation, thermal and catalytic studies of N-substituted piperazine, morpholine and thiomorpholine with some metal ions

    Science.gov (United States)

    Kacan, Mesut; Turkyilmaz, Murat; Karabulut, Ferhat; Altun, Ozlen; Baran, Yakup

    2014-01-01

    Several Cu(II), Pt(II) and Ni(II) complexes of N-substituted, piperazine (NN donor), morpholine (NO donor) and thiomorpholine (NS donor) derivatives were synthesized and their thermal behavior and catalytic activity in epoxidation reaction of cis-diphenylethylene were studied using oxygen sources NaOCl. The coordination compounds of Cu(II), Pt(II) and Ni(II) having general formula [MLCl]Cl, [ML2l]Cl2 or [ML]Cl2 with tetra coordinated geometry around metal ions have been isolated as solid. All the ligands and complexes were identified by spectroscopic methods and elemental analysis, magnetic measurements, electrical conductance and thermal analysis. A square planer structures have been proposed for all complexes. The thermal stability of the complexes discussed in terms of ligands donor atoms, geometry and central metal ions. The complexes have a similar thermal behavior for the selected metal ions. The thermogravimetric analyses suggest high thermal stability for most complexes followed by thermal decomposition in different steps. The decomposition processes were observed as water elimination, chloride anion removal and degradation of the organic ligands. Catalytic ability of the complexes were examined and found that all the complexes can effectively catalyze the epoxidation of cis-stilbene with NaOCl.

  16. Inorganic base-catalyzed formation of antivirally active N-substituted benzamides from ?-amido sulfones and N-nucleophile

    Directory of Open Access Journals (Sweden)

    Wang Zhenchao

    2011-05-01

    Full Text Available Abstract Background Heteronucleophiles as well as carbanionic reagents can be used to react with ?-amido sulfones, thus giving the opportunity to prepare a large array of amino derivatives. Since, novel 1,3,4-oxadiazole-2-thiol derivatives can serve as potent nucleophiles, we employed 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the nucleophilic source of nitrogen in the reaction with ?-amido sulfones. Results A series of N-substituted benzamides bearing 1,3,4-oxadiazol unit were prepared for the first time by the reaction of in situ generated protected imine from ?-amido sulfones with 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the source of nitrogen nucleophile. Some of the synthesized products displayed favourable antiviral activity against cucumber mosaic virus (CMV in preliminary antiviral activity tests. The title compounds 5c, 5o and 5r revealed curative activity of 42.2%, 48.7% and 40.5%, respectively against CMV (inhibitory rate compared to the commercial standard Ningnanmycin (53.4% at 500 ?g/mL. Conclusion A practical synthetic route to N-benzoyl-?-amido sulfones by the reaction of 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the source of nitrogen nucleophiles with in situ generated protected imine from N-benzoyl-?-amido sulfones is presented. The reaction catalyzed by an inorganic base has considerable significance to exploit the potential of ?-amido sulfones in organic synthesis.

  17. Design, synthesis and in vitro antitumor activity of novel N-substituted-4-phenyl/benzylphthalazin-1-ones.

    Science.gov (United States)

    Eldehna, Wagdy M; Ibrahim, Hany S; Abdel-Aziz, Hatem A; Farrag, Noha N; Youssef, Mohieldin M

    2015-01-01

    A novel series of N-substituted-4-phenylphthalazin-1-ones 14a-g bearing different anilines at the N-2 of phthalazin-1-one scaffold via acetyl-flexible linker was designed and synthesized for the development of potential anticancer agents. Compounds 19a-g were synthesized by insertion of methylene (CH2) bridge at C4-position of 14a-g to provide a flexibility for the phenyl group. The newly synthesized compounds 14a-g and 19a-g were evaluated for their anti-proliferative activity against three human tumor cell lines HepG2 hepatocellular carcinoma, HT-29 colon cancer and MCF-7 breast cancer. In particular, HepG2 and HT-29 cancer cell lines were more susceptible to the synthesized derivatives. Compound 19d (IC50 = 1.2 ± 0.09 ?M) was found to be the most potent derivative against HepG2 as it was 2.9 times more active than doxorubicin (IC50 = 3.45 ± 0.54) and sorafenib (IC50 = 3.5 ± 1.04 ?M). Compounds 14e, 14g, 19d and 19g with IC50 = (3.29 ± 0.45), (3.50 ± 0.846), (1.20 ± 0.09) and (3.52 ± 0.70) ?M, respectively, were found to be active candidates against HepG2 cancer cells. Compounds 14e, 14g, 19d and 19g were able to induce apoptosis in HepG2, this was assured by; the significant increase in the percentage of annexin V-FITC-positive apoptotic cells (UR + LR), the down-regulation of the anti-apoptotic protein Bcl-2 and the up-regulation of the pro-apoptotic protein Bax, in addition to boosting caspase-3 levels. Moreover, cytotoxicity evaluation of the newly synthesized compounds in HT-29 revealed that compounds 14e, 14f, 19e and 19f (IC50 = 3.05 ± 0.78, 4.02 ± 1.18, 3.68 ± 0.79 and 2.98 ± 0.47 ?M, respectively) were more potent than doxorubicin (IC50 = 7.70 ± 1.78 ?M). PMID:25462265

  18. Aryl diazonium salts new coupling agents and surface science

    CERN Document Server

    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

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

    Science.gov (United States)

    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 ?-O-4, ?-O-4, and 4-O-5 lignin model compounds is also illustrated, which highlights the advance toward the goal of lignin conversion. PMID:25317950

  20. Palladium-catalyzed ?-arylation of arylketones at low catalyst loadings.

    Science.gov (United States)

    Marelli, Enrico; Corpet, Martin; Davies, Sian R; Nolan, Steven P

    2014-12-22

    A general catalytic protocol for the ?-arylation of aryl ketones has been developed. It involves the use of a preformed, bench-stable Pd-N-heterocyclic carbene pre-catalyst bearing IHept as an ancillary ligand, and allows the coupling of various functionalized coupling partners at very low catalyst loading. Careful choice of the solvent/base system was crucial to obtain optimum catalyst performance. The pre-catalyst was also successfully tested in the synthesis of an industrially relevant compound. PMID:25414140

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

    International Nuclear Information System (INIS)

    N, N',N, N'-Tetramethyl tetra-2,3-pyridinoporphyrazinato copper(II) methyl sulfate ([Cu(2,3-tmtppa)](MeSO4)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 H2O. The catalyst was recovered and reused at least four times, maintaining its efficiency. (author)

  2. Experimental and theoretical study of [N-substituted] p-aminoazobenzene derivatives as corrosion inhibitors for mild steel in sulfuric acid solution

    Science.gov (United States)

    Shihab, Mehdi Salih; Al-Doori, Hanan Hussien

    2014-11-01

    [N-substituted] p-aminoazobenzene derivatives (1), (2), (3), (4) and (5) were prepared and investigated as corrosion inhibitors for mild steel in 1 M H2SO4 solution by weight loss measurements. It has been observed that the corrosion rate decreases, inhibition efficiencies increase and surface coverage degree increases with increasing inhibitor concentration. Inhibition efficiencies for prepared compounds were ordered: (1) > (2) > (5) > (4) > (3) with the highest inhibiting efficiency of 63% for 10-3 M. The values of ?Gadso are showing physisorption effect for all prepared compounds. Semiempirical molecular orbital calculations for (1), (2), (3), (4) and (5) could be used as a useful tool to obtain information for explaining the nature of interaction between the metal surface and the organic molecule as a corrosion inhibitor.

  3. Synthesis and biological activity of a new class of sulfone-linked pyrrolylpyrazoles and pyrrolylisoxazoles from methyl-3-aryl-2-(E-arylethenesulfonyl)acrylate.

    Science.gov (United States)

    Padmavathi, Venkatapuram; Radha Lakshmi, Thunga; Mahesh, Konda; Padmaja, Adivireddy

    2009-11-01

    A new class of sulfone-linked bis heterocycles, methyl-3-(4'-aryl-1'H-pyrazol-3'-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (8), methyl-3-(1'-phenyl-3',5'-diaryl-1'H-pyrazol-4'-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (9) and methyl-3-(3',5'-diarylisoxazol-4'-ylsulfonyl)-4-aryl-3H-pyrrole-3-carboxylate (10) were prepared by the regioselective reaction of methyl-3-aryl-2-(E-arylethenesulfonyl)acrylate (2) with tosylmethyl isocyanide followed by fuctionalization of olefin moiety with 1,3-dipolar reagents. The lead compounds were tested for their antimicrobial activity. PMID:19881267

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

    Directory of Open Access Journals (Sweden)

    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 ?M. 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.

  5. Solid-phase exchange radioiodination of aryl iodides. Facilitation by ammonium sulfate

    International Nuclear Information System (INIS)

    A mild and simple technique for the synthesis of aryl radioiodides of high specific activity involving a solid-phase exchange between no-carrier-added radioiodide and unactivated aryl iodides is described. Mildly acidic, oxidizing conditions, provided by the in situ thermal decomposition of ammonium sulfate, appear to be necessary for the success of the exchange. Typical isolated radiochemical yields of >70% have been obtained for a variety of aryl iodides, including various aralkyl amines, guanidines, carboxylic acids, and amino acids. Specific activities of up to 100 Ci/mmol of our model compound, (m-[125I]iodobenzyl)guanidine, have been achieved. Preliminary experiments suggest that, with this technique interhalogen exchange of aryl bromides with radioiodine is a feasible approach to the preparation of no-carrier-added aryl radioiodides

  6. Functionality of aryl hydrocarbon receptors (AhR1 and AhR2) of white sturgeon (Acipenser transmontanus) and implications for the risk assessment of dioxin-like compounds.

    Science.gov (United States)

    Doering, Jon A; Farmahin, Reza; Wiseman, Steve; Kennedy, Sean W; Giesy, John P; Hecker, Markus

    2014-07-15

    Worldwide, populations of sturgeons are endangered, and it is hypothesized that anthropogenic chemicals, including dioxin-like compounds (DLCs), might be contributing to the observed declines in populations. DLCs elicit their toxic action through activation of the aryl hydrocarbon receptor (AhR), which is believed to regulate most, if not all, adverse effects associated with exposure to these chemicals. Currently, risk assessment of DLCs in fishes uses toxic equivalency factors (TEFs) developed for the World Health Organization (WHO) that are based on studies of embryo-lethality with salmonids. However, there is a lack of knowledge of the sensitivity of sturgeons to DLCs, and it is uncertain whether TEFs developed by the WHO are protective of these fishes. Sturgeons are evolutionarily distinct from salmonids, and the AhRs of sturgeons differ from those of salmonids. Therefore, this study investigated the sensitivity of white sturgeon (Acipenser transmontanus) to DLCs in vitro via the use of luciferase reporter gene assays using COS-7 cells transfected with AhR1 or AhR2 of white sturgeon. Specifically, activation and relative potencies (RePs) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachloro-dibenzofuran, 2,3,7,8-tetrachloro-dibenzofuran, 3,3',4,4',5-pentachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, and 2,3,3',4,4'-pentachlorobiphenyl were determined for each AhR. It was demonstrated that white sturgeon expresses AhR1s and AhR2s that are both activated by DLCs with EC50 values for 2,3,7,8-TCDD that are lower than those of any other AhR of vertebrates tested to date. Both AhRs of white sturgeon had RePs for polychlorinated dibenzofurans more similar to TEFs for birds, while RePs for polychlorinated biphenyls were most similar to TEFs for fishes. Measured concentrations of select DLCs in tissues of white sturgeon from British Columbia, Canada, were used to calculate toxic equivalents (TEQs) by use of TEFs for fishes used by the WHO and TCDD equivalents (TCDD-EQs) via the use of RePs for AhR2 of white sturgeon as determined by transfected COS-7 cells. TCDD-EQs calculated for endangered populations of white sturgeon were approximately 10-fold greater than TEQs and were within ranges known to cause adverse effects in other fishes, including other species of sturgeons. Therefore, TEFs used by the WHO might not adequately protect white sturgeon, illuminating the need for additional investigation into the sensitivity of these fish to DLCs. PMID:24950391

  7. Stability constants of complexes of the N-substituted anthranilic acids with lanthanides

    International Nuclear Information System (INIS)

    The interaction between trivalent metal ions La(III), Pr(III), Nd(III), Gd(III), Dy(III) and Y(III) with N-substituted anthranilic acids have been studied in 50 per cent ethanol-water medium at various ionic strengths and at constant temperature, following potentiometric technique. The order of stability constants with respect to metal ions has been found to be La N-Me. An. A. > N-Et. An. A > N-Ph.An. A. (author). 2 tabs., 11 refs

  8. Synthesis, growth and characterization of new 1,3,4 -thiadiazole-5-(n-substituted)-sulfonamides cristals

    Scientific Electronic Library Online (English)

    G.E., Camí; M.del C., Ramírez de Arellano; S., Fustero; J.C., Pedregosa.

    2006-12-01

    Full Text Available SciELO Argentina | Language: English Abstract in spanish Nuevas 1,3,4-tiadiazol-5-(N-substituidas)-sulfonamidas, inhibidores de anhidrasa carbónica, fueron obtenidas incorporando los grupos N-ciclohexil, N-benzil and N-[sec-butil], por una síntesis optimizada y monocristales de las mismas fueron crecidos desde alcohol absoluto por evaporación lenta a temp [...] eratura ambiente hasta dimensiones adecuadas para medidas de DRX. Los datos estructurales de estos compuestos monoclínicos son comparados con los de otras fases relacionadas. El grupo sulfonil presenta una geometría tetraédrica distorsionada alrededor del átomo de S. Los diferentes sustituyentes introducidos no producen modificaciones en la estructura del anillo 1,3,4-tiadiazol. El análisis térmico de las tres fases muestra descomposición total a temperaturas por encima del punto de fusión. Los espectros FTIR confirman la formación de los compuestos y es el primer aporte sobre el conocimiento de la unión puente hidrógeno NH...N en estas sulfonamidas. Abstract in english New 1,3,4-thiadiazole-5-(N-substituted)-sulfonamide derivatives incorporating N-cyclohexyl, N-benzyl and N-[sec-butyl] moieties, carbonic anhydrase inhibitors, have been obtained by an optimized synthesis. Single crystals of these sulfonamides have been successfully grown up to suitable dimensions f [...] or X-ray diffraction measurements by slow evaporation of solvent at room temperature. Structural data for these monoclinic compounds are compared with those of related phases. The sulfonyl moiety presents a distorted tetrahedral arrangement around the S atom. The different groups introduced cause no observable modifications of the 1,3,4-thiadiazole ring structure. Thermal analysis show total sample degradation at temperatures higher than that of the melting point of the three phases. The FTIR spectra confirm the compounds formation and provide a first insight on the modes of NH…N hydrogen bond in these sulfonamides.

  9. Pd-catalyzed carbonylative ?-arylation of aryl bromides: scope and mechanistic studies.

    Science.gov (United States)

    Nielsen, Dennis U; Lescot, Camille; Gøgsig, Thomas M; Lindhardt, Anders T; Skrydstrup, Troels

    2013-12-23

    Reaction conditions for the three-component synthesis of aryl 1,3-diketones are reported applying the palladium-catalyzed carbonylative ?-arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)2] (dba=dibenzylideneacetone) as the palladium source and 1,3-bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two-chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO-releasing compound, 9-methylfluorene-9-carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3-diketones. A mechanistic investigation of this transformation relying on 31P and 13C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)2] and DPPP was only reactive towards 4-bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative-addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3-diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd0 precursor, [Pd(?3-1-PhC3H4)(?5-C5H5)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)2], its oxidative addition with 4-bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative ?-arylation of 4-bromoanisole with either catalytic or stoichiometric [Pd(?3-1-PhC3H4)(?5-C5H5)] over a short reaction time, led to the 1,3-diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)2] as the Pd source. PMID:24265100

  10. Reaction of aryl diazonium tetrafluoro borates with allyl methacrylate in the presence of rhodanide-anion

    International Nuclear Information System (INIS)

    Reaction of aryl diazonium tetrafluoro borates (I) with allyl ester of methacrylic acid in the water-acetone (1:5) medium is studied by means of IR spectroscopy and 1H NMR. It is established that (I) reacts with aryl methacrylate in the presence of rhodanide-anion and catalytic quantities of copper salts with the formation of allyl esters of 2-thiocyanato-2-methyl-3-aryl propionic acids with the yield of 32-56%. Allyl fragment of biunsaturated compound shows no reaction under the tested conditions

  11. Roles of the Enantioselective Glutathione S-Transferases in Cleavage of ?-Aryl Ether

    OpenAIRE

    Masai, Eiji; Ichimura, Atsushi; Sato, Yusuke; Miyauchi, Keisuke; Katayama, Yoshihiro; Fukuda, Masao

    2003-01-01

    Cleavage of the ?-aryl ether linkage is the most important process in lignin degradation. Here we characterize the three tandemly located glutathione S-transferase (GST) genes, ligF, ligE, and ligG, from low-molecular-weight lignin-degrading Sphingomonas paucimobilis SYK-6, and we describe the actual roles of these genes in the ?-aryl ether cleavage. Based on the identification of the reaction product by electrospray ionization-mass spectrometry, a model compound of ?-aryl ether, ?-(2-met...

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    Juana Andrea Ibacache; Virginia Delgado; Julio Benites; Cristina Theoduloz; Verónica Arancibia; Muccioli, Giulio G.; Valderrama, Jaime A.

    2014-01-01

    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-thi...

  14. Synthesis of 2-Aryl and 3-Aryl Benzo[b]furan Thioethers Using Aryl Sulfonyl Hydrazides as Sulfenylation Reagents.

    Science.gov (United States)

    Zhao, Xia; Zhang, Lipeng; Lu, Xiaoyu; Li, Tianjiao; Lu, Kui

    2015-03-01

    An efficient, metal-free protocol used to synthesize aryl benzo[b]furan thioethers based on the I2-catalyzed cross-coupling of benzo[b]furans as well as the electrophilic cyclization of 2-alkynylphenol derivatives with aryl sulfonyl hydrazides was developed. Various 2-aryl and 3-aryl benzo[b]furan thioethers were obtained in moderate to good yields. PMID:25674835

  15. Palladium-catalyzed ?-arylation of sultams with aryl and heteroaryl iodides.

    Science.gov (United States)

    René, Olivier; Fauber, Benjamin P; Malhotra, Sushant; Yajima, Herbert

    2014-07-01

    Palladium(0)-catalyzed conditions for the ?-arylation of sultams with aryl and heteroaryl iodides have been developed. Arylation of 3-substituted 1,3-propanesultams gave rise to high yields and high diastereomeric ratios, leading to the thermodynamically favored cis product. The arylation was broadly applicable to various electron-rich and electron-poor (hetero)aromatic iodides. PMID:24937120

  16. Identification and expression of aryl hydrocarbon receptors (AhR1 and AhR2) provide insight in an evolutionary context regarding sensitivity of white sturgeon (Acipenser transmontanus) to dioxin-like compounds.

    Science.gov (United States)

    Doering, Jon A; Wiseman, Steve; Beitel, Shawn C; Giesy, John P; Hecker, Markus

    2014-05-01

    Sturgeons are ancient fishes, which are endangered in many parts of the world. Due to their benthic nature and longevity, sturgeon are at great risk of exposure to bioaccumulative contaminants such as dioxin-like compounds (DLCs). Despite their endangered status, little research has been conducted to characterize the relative sensitivity of sturgeons to DLCs. Proper assessment of risk of DLCs posed to these fishes therefore, requires a better understanding of this sensitivity and the factors that are driving it. Adverse effects associated with exposure to DLCs are mediated by the aryl hydrocarbon receptor (AhR). This study identified and characterized two distinct AhRs, AhR1 and AhR2, in white sturgeon (Acipenser transmontanus) for the first time as a first step in studying the relative sensitivities of sturgeons to DLCs. Furthermore, tissue-specific expression of both AhRs under basal conditions and in response to exposure to the model DLC, ?-naphthoflavone (?NF), was determined. The sequence of amino acids of AhR1 of white sturgeon had greater similarity to AhRs of tetrapods, including amphibians, birds, and mammals, than to AhR1s of other fishes. The sequence of amino acids in the ligand binding domain of the AhR1 had greater than 80% similarity to AhRs known to bind DLCs and was less similar to AhRs not known to bind DLCs. AhR2 of white sturgeon had greatest similarity to AhR2 of other fishes. Profiles of expression of AhR1 and AhR2 in white sturgeon were distinct from those known in other fishes and appear more similar to profiles observed in birds. Expressions of both AhR1 and AhR2 of white sturgeon were greatest in liver and heart, which are target organs for DLCs. Furthermore, abundances of transcripts of AhR1 and AhR2 in all tissues from white sturgeon were greater than controls (up to 35-fold) following exposure to ?NF. Based upon both AhRs having similar abundances of transcript in target organs of DLC toxicity, both AhRs being up-regulated following exposure to ?NF, and both AhRs having greatest similarity to AhRs known to bind DLCs, it is hypothesized that both AhR1 and AhR2 of white sturgeon might mediate effects of DLCs in this species. Since current risk assessments are based on data derived largely from highly divergent fishes within the Salmonidae, presence of two functional AhRs in white sturgeon, one of which has greatest similarity to AhRs of birds, might have significant implications for the sensitivity of sturgeons to DLCs compared to other fishes. PMID:24632312

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  18. Potency and species specificity of aryl hydrocarbon receptor ligands

    OpenAIRE

    Wall, Richard John

    2012-01-01

    The aryl hydrocarbon receptor (AhR) binds a wide range of structurally diverse compounds such as halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls which are abundant in the environment. Activation of AhR leads to the regulation of a battery of xenobiotic enzymes including cytochrome P4501A1 (CYP1A1). The purely chlorinated compounds feature in the World Health Organisation’s (WHO) evaluation of dioxin-like compounds derived from a meta-analysis of previous potency data (toxic equiv...

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

    Science.gov (United States)

    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

  20. Palladium-Catalyzed Thiocarbonylation of Aryl, Vinyl, and Benzyl Bromides

    DEFF Research Database (Denmark)

    Burhardt, Mia; Ahlburg, Andreas

    2014-01-01

    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.

  1. A Structure-Activity Study with Aryl Acylamidases

    OpenAIRE

    Villarreal, David T.; Turco, Ronald F.; Konopka, Allan

    1994-01-01

    We examined the relationship between chemical structure and biodegradability of acylanilide herbicides by using a set of model compounds. Four bacterial isolates (one gram-negative and three gram-positive) that grew on acetanilide were used. These soil isolates cleaved the amide bond of acetanilide via an aryl acylamidase reaction, producing aniline and the organic acid acetate. A series of acetanilide analogs with alkyl substitutions on the nitrogen atom or the aromatic ring were tested for ...

  2. SYNTHESIS OF N-SUBSTITUTED CARBONYLAMINO-1,2,3,6-TETRAHYDROPYRIDINES AS POTENTIAL ANTI-INFLAMMATORY AGENTS

    OpenAIRE

    Ghaffari, Mohammad A.; Ardley, Tiffany W.; Gangapuram, Madhavi; Redda, Kinfe K.

    2011-01-01

    Several N-substituted carbonyl/sulfonylamino-1,2,3,6-tetrahydropyridines (5a–i and 9a, b) were synthesized via sodium borohydride reduction of the corresponding N-substitutedimino-pyridinium ylides (4a–i and 8a, b) in absolute ethanol.

  3. Establishing dependences between different lipophilic parameters of new potentially biologically active N-substituted-2-phenylacetamide derivatives by applying multivariate methods.

    Science.gov (United States)

    Vastag, Gyöngyi; Apostolov, Suzana; Matijevi?, Borko; Petrovi?, Slobodan

    2015-02-01

    Lipophilicity, a very important parameter in the potential biological activities of molecules, was investigated for newly synthesized N-substituted-2-phenylacetamide derivatives. The determination was carried out in two ways: first experimentally, by applying thin-layer chromatography (TLC) on reversed-phase TLC (RPTLC) RP18F254s in the presence of one protic (methanol) and one aprotic solvent (acetonitrile) and then mathematically, by using different software packages. The intercept of the linear dependence between volume fractions of the organic solvent and the retention parameters obtained by TLC is known as the retention chromatographic constant, R(M)(0), while the slope represents the m value. In order to establish the dependences between the partition coefficient, log P as the standard measure of lipophilicity and the alternative lipophilic parameters obtained experimentally by TLC, R(M)(0) and m values, linear regression analysis and multivariate methods, cluster analysis (CA) and principal component analysis (PCA), were used. All applied methods gave approximately similar results. Although there is a linear dependence between the two chromatographic parameters, the retention constant, R(M)(0), and the m values, only R(M)(0) shows suitable similarity with the standard measure of lipophilicity of the investigated N-substituted-2-phenylacetamide derivatives at the given conditions. The existence of this resemblance proves that the chromatographic retention constant, R(M)(0), obtained by RPTLC could be successfully used for the description of lipophilicity of investigated compounds. On the other hand, the results confirmed that the applied linear regression analysis and the multivariate analysis (CA and PCA) have the ability to compare lipophilic parameters of the investigated phenylacetamide derivatives obtained in different ways. PMID:24981978

  4. Radioimmunoassay for anileridine, meperidine, and other N-substituted phenylpiperidine carboxylic acid esters

    International Nuclear Information System (INIS)

    Antibodies that bind an 125I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50 percent inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 104, major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay

  5. Radioimmunoassay for anileridine, meperidine, and other N-substituted phenylpiperidine carboxylic acid esters

    Energy Technology Data Exchange (ETDEWEB)

    Van Vunakis, H.; Freeman, D.S.; Gjika, H.B.

    1975-10-01

    Antibodies that bind an /sup 125/I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50 percent inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 10/sup 4/, major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay.

  6. Anaerobic biotransformation of roxarsone and related N-substituted phenylarsonic acids

    Science.gov (United States)

    Cortinas, I.; Field, J.A.; Kopplin, M.; Garbarino, J.R.; Gandolfi, A.J.; Sierra-Alvarez, R.

    2006-01-01

    Large quantities of arsenic are introduced into the environment through land application of poultry litter containing the organoarsenical feed additive roxarsone (3-nitro-4-hydroxyphenylarsonic acid). The objective of this study was to evaluate the bioconversion of roxarsone and related N-substituted phenylarsonic acid derivatives under anaerobic conditions. The results demonstrate that roxarsone is rapidly transformed in the absence of oxygen to the corresponding aromatic amine, 4-hydroxy-3-aminophenylarsonic acid (HAPA). The formation of HAPA is attributable to the facile reduction of the nitro group. Electron-donating substrates, such as hydrogen gas, glucose, and lactate, stimulated the rate of nitro group reduction, indicating a microbial role. During long-term incubations, HAPA and the closely related 4-aminophenylarsonic acid (4-APA) were slowly biologically eliminated by up to 99% under methanogenic and sulfate-reducing conditions, whereas little or no removal occurred in heat-killed inoculum controls. Arsenite and, to a lesser extent, arsenate were observed as products of the degradation. Freely soluble forms of the inorganic arsenical species accounted for 19-28% of the amino-substituted phenylarsonic acids removed. This constitutes the first report of a biologically catalyzed rupture of the phenylarsonic group under anaerobic conditions. ?? 2006 American Chemical Society.

  7. Chemometric approach in studying of the retention behavior and lipophilicity of potentially biologically active N-substituted-2-phenylacetamide derivatives

    Scientific Electronic Library Online (English)

    Gyöngyi Gy., Vastag; Suzana Lj., Apostolov; Borko M., Matijevi& #263; ; Aleksandar D., Marinkovi& #263; .

    1948-19-01

    Full Text Available A atividade biológica potencial de moléculas depende largamente da sua lipofilicidade. A lipofilicidade de derivados de 2-fenilacetamida N-substituída foi investigada experimentalmente, aplicando cromatografia em camada delgada em fase inversa (RP-TLC em RP 18 F254s) na presença de etanol e de dioxa [...] no, e usando pacotes de software. A fim de estabelecer a dependência entre a lipofilicidade obtida de diferentes formas foram usados análise de regressão linear e métodos multivariados. Agrupamentos aproximadamente semelhantes dos parâmetros lipofílicos e dos compostos testados foram registados no caso de ambos os métodos quimiométricos usados. Todos os resultados obtidos confirmam o fato de que as análises de regressão linear e multivariada aplicadas oferecem oportunidades para comparar os dados sobre a retenção cromatográfica e parâmetros lipofílicos dos derivados de fenilacetamida investigados. Os resultados sugerem que a lipofilicidade das moléculas estudadas depende largamente da natureza dos substituintes ligados ao átomo de nitrogênio e, por outro lado, que as constantes retenção cromatográfica, R M0, determinada pelo método de RP-TLC, são semelhantes à medida padrão de lipofilicidade, log P, o que torna este método adequado para a previsão de lipofilicidade. Abstract in english The potential biological activity of a molecule largely depends on its lipophilicity. The lipophilicity of derivatives of N-substituted-2-phenylacetamide was investigated experimentally, by applying thin-layer chromatography on reversed phase (RP-TLC on RP 18 F254s) in the presence of ethanol and di [...] oxane and by using relevant software packages. In order to establish dependence between lipophilicity obtained in different ways, linear regression analysis and multivariate methods were used. Approximately similar groupings of lipophilic parameters and tested compounds were registered in case of both chemometric methods. The obtained results confirm the fact that the applied linear regression analysis and multivariate analysis provide opportunities for comparing chromatographic retention data and lipophilic parameters of the investigated phenylacetamide derivatives. Results suggest that the lipophilicity of investigated molecules largely depends on the nature of the substituents linked to nitrogen atom and on the other hand that the chromatographic retention constants, R M0, determined by RP-TLC method, are similar to the standard measure of lipophilicity, log P, which makes this method appropriate for predicting lipophilicity.

  8. Synthesis, characterization and antiproliferative activity of ?-aryl-?-iodo-?-lactones

    Science.gov (United States)

    Wzorek, Alicja; Gawdzik, Barbara; G?adkowski, Witold; Urbaniak, Mariusz; Bara?ska, Anita; Mali?ska, Maura; Wo?niak, Krzysztof; Kempi?ska, Katarzyna; Wietrzyk, Joanna

    2013-09-01

    A convenient pathway for the synthesis of new of ?-aryl-?-iodo-?-lactones is described. The synthetic route led to both cis and trans isomers which were separated by column chromatography or crystallization. The structures of synthesized compounds were confirmed by spectroscopic methods: IR, NMR and HR-MS. For lactones with naphthyl ring (6e and 7e) the crystal structures were also obtained. The lactones were screened for biological evaluation against cancer line HL-60 (human promyelocytic leukemia). The tests showed that the presence of substituent at the benzene ring does not significantly affect the antiproliferative activity of the compound.

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Compound

    Science.gov (United States)

    Suzumura, Akitoshi; Watanabe, Masaki; Nagasako, Naoyuki; Asahi, Ryoji

    2014-06-01

    Recently, Cu-based chalcogenides such as Cu3SbSe4, Cu2Se, and Cu2SnSe3 have attracted much attention because of their high thermoelectric performance and their common feature of very low thermal conductivity. However, for practical use, materials without toxic elements such as selenium are preferable. In this paper, we report Se-free Cu3SbS4 thermoelectric material and improvement of its figure of merit ( ZT) by chemical substitutions. Substitutions of 3 at.% Ag for Cu and 2 at.% Ge for Sb lead to significant reductions in the thermal conductivity by 37% and 22%, respectively. These substitutions do not sacrifice the power factor, thus resulting in enhancement of the ZT value. The sensitivity of the thermal conductivity to chemical substitutions in these compounds is discussed in terms of the calculated phonon dispersion and previously proposed models for Cu-based chalcogenides. To improve the power factor, we optimize the hole carrier concentration by substitution of Ge for Sb, achieving a power factor of 16 ?W/cm K2 at 573 K, which is better than the best reported for Se-based Cu3SbSe4 compounds.

  12. 1-Aryl-4-silylmethyl[60]fullerenes: synthesis, properties, and photovoltaic performance.

    Science.gov (United States)

    Matsuo, Yutaka; Oyama, Hiromi; Soga, Iwao; Okamoto, Toshihiro; Tanaka, Hideyuki; Saeki, Akinori; Seki, Shu; Nakamura, Eiichi

    2013-01-01

    The efficient nucleophilic addition of aryl Grignard reagents (aryl=4-MeOC(6)H(4), 4-Me(2)NC(6)H(4), Ph, 4-CF(3)C(6)H(4), and thienyl) to C(60) in the presence of DMSO produced 1,2-arylhydro[60]fullerenes after acid treatment. The reactions of the anions of these arylhydro[60]fullerenes with either dimethylphenylsilylmethyl iodide or dimethyl(2-isopropoxyphenyl)silylmethyl iodide yielded the target compounds, 1-aryl-4-silylmethyl[60]fullerenes. The properties and structures of these 1-aryl-4-silylmethyl[60]fullerenes (aryl=4-MeOC(6)H(4), thienyl) were examined by electrochemical studies, X-ray crystallography, flash-photolysis time-resolved microwave-conductivity (FP-TRMC) measurements, and electron-mobility measurements by using a space-charge-limited current (SCLC) model. Organic photovoltaic devices with a polymer-based bulk heterojunction structure and small-molecule-based p-n and p-i-n heterojunction configurations were fabricated by using 1-aryl-4-silylmethyl[60]fullerenes as an electron acceptor. The most efficient device exhibited a power-conversion efficiency of 3.4% (short-circuit current density: 8.1 mA/cm(2), open-circuit voltage: 0.69 V, fill factor: 0.59). PMID:23023947

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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).

    Science.gov (United States)

    Pariseau, Julie; McKenna, Patricia; Aboelkhair, Mohammed; Saint-Louis, Richard; Pelletier, Emilien; Davidson, T Jeffrey; Tremblay, Réjean; 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

  16. Palladium-Catalyzed Carbonylative ?-Arylation to ?-Ketonitriles

    DEFF Research Database (Denmark)

    Schranck, Johannes; Burhardt, Mia

    2014-01-01

    A carbonylative ?-arylation process employing unactivated nitriles for the first time is described. The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting ?-ketonitriles are obtained in good to excellent yields. The methodology also allows for a convenient (13) C-labelling of the generated carbonyl moiety.

  17. Synthesis and antiamoebic activity of new 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives and their Pd(II) complexes.

    Science.gov (United States)

    Budakoti, Asha; Abid, Mohammad; Azam, Amir

    2006-01-01

    Some 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives (L), 1-8 were synthesized by a base-catalyzed Claisen-Schmidt condensation of benzaldehyde with acetophenone followed by cyclization with various N-4 substituted thiosemicarbazides. The palladium(II) complexes [PdLCl2], 1a-8a of these ligands were obtained by reacting them with [Pd(DMSO)2Cl2]. All compounds have been characterized by means of elemental analyses, electronic, IR, 1H NMR and mass spectroscopic data, while the complexes have additionally been characterized by thermogravimetric patterns. The in vitro antiamoebic activity was evaluated against the HM1:IMSS strain of Entamoeba histolytica and the results were compared with the standard drug, metronidazole. The preliminary test results showed that the complexes had better antiamoebic activity than their respective ligands. Moreover, the complexes showed better inhibition of the test organism. The results suggest that the ligands 4, 7 and the complexes 2a-4a, 6a-8a were found with IC50 lower than that of the standard drug metronidazole and thus are better inhibitor of growth of E. histolytica. PMID:16300860

  18. Reductive cleavage of N-substituted aromatic amides as tert-butyl acylcarbamates

    OpenAIRE

    Ragnarsson, Ulf; Grehn, Leif; Maia, Herna?ni L. S.; Monteiro, Lui?s S.

    2002-01-01

    Synthetic and spectroscopic details related to a set of heteroaromatic N-benzyl carboxamides and especially the corresponding tert-butyl acylcarbamates are reported. These compounds were required to study the postulated effect of various heterocycles (pyridine and pyrazine with and without condensed benzene rings) on the cleavage of acyl-N bonds by reduction. All compounds were initially characterized by cyclic voltammetry which indicated various degrees of facilitated reduction, reflecting a...

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

    International Nuclear Information System (INIS)

    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 ?g-ml-1 for IIIa-I and 5 ?g-ml-1 for IIIm,n. (authors). 24 refs., 4 figs., 5 tabs

  20. Catalytic enantioselective aziridoarylation of aryl cinnamyl ethers toward synthesis of trans-3-amino-4-arylchromans.

    Science.gov (United States)

    Hajra, Saumen; Sinha, Debarshi

    2011-09-16

    Catalytic enantioselective one-pot aziridoarylation reaction of aryl cinnamyl ethers has been demonstrated in detail. Combination of suitable copper catalyst and chiral bis-oxazoline ligand was found to be very efficient for asymmetric aziridination followed by intramolecular arylation (Friedel-Crafts) reaction to provide a general and direct method for the synthesis of trans-3-amino-4-arylchromans with high regio-, diastereo- (dr > 99:1), and enantioselectivity (up to 95% ee) with moderate yield. trans-3-Amino-4-arylchroman is an advanced intermediate for the synthesis of chromenoisoquinoline compounds such as doxanthrine, a potent and selective full agonist for the dopamine-D(1) receptor. PMID:21797274

  1. Nickel-Catalyzed Amination of Aryl Chlorides and Sulfamates in 2-Methyl-THF.

    Science.gov (United States)

    Fine Nathel, Noah F; Kim, Junyong; Hie, Liana; Jiang, Xingyu; Garg, Neil K

    2014-09-01

    The nickel-catalyzed amination of aryl O-sulfamates and chlorides using the green solvent 2-methyl-THF is reported. This methodology employs the commercially available and air-stable precatalyst NiCl2(DME), is broad in scope, and provides access to aryl amines in synthetically useful yields. The utility of this methodology is underscored by examples of gram-scale couplings conducted with catalyst loadings as low as 1 mol % nickel. Moreover, the nickel-catalyzed amination described is tolerant of heterocycles and should prove useful in the synthesis of pharmaceutical candidates and other heteroatom-containing compounds. PMID:25243095

  2. A Facile Synthesis of N-H- and N-Substituted Acridine-1,8-diones under Sonic Condition

    Science.gov (United States)

    Sudha, S.; Pasha, M. A.

    2013-01-01

    Synthesis of an assembly of structurally important N-H- and N-substituted acridine-1,8-diones by CAN (ceric ammonium nitrate) catalysed one-pot four-component reaction of electron-deficient and electron-rich aromatic aldehydes and aromatic amines or ammonium acetate and dimedone or cyclohexyl-1,3-diones at 26°C under sonic condition is reported. The method is clean and energy efficient as it uses a greener method and an eco-friendly catalyst. PMID:24501587

  3. Rational Synthesis of AB-Type N-Substituted Core-Functionalized Naphthalene Diimides (cNDIs).

    Science.gov (United States)

    Berezin, Andrey A; Sciutto, Andrea; Demitri, Nicola; Bonifazi, Davide

    2015-04-17

    Acid-mediated transformation of tetraethyl 2,6-diethoxynaphthalene-1,4,5,8-tetracarboxylate selectively affords the core-substituted naphthalene-anhydride-ester (cNAE) in quantitative yield. This anhydride can be selectively converted into hetero-N-substituted core-functionalized naphthalene diimides (cNDIs) through sequential condensation reactions in the presence of the precursor amine with very high isolated yields over four steps. The approach can be applied to prepare a large variety of heterocyclic, aromatic, and aliphatic heterodiimides. PMID:25822286

  4. 2-(Hetero(aryl)methylene)hydrazine-1-carbothioamides as potent urease inhibitors.

    Science.gov (United States)

    Saeed, Aamer; Imran, Aqeel; Channar, Pervaiz A; Shahid, Mohammad; Mahmood, Wajahat; Iqbal, Jamshed

    2015-02-01

    A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including two aryl derivatives was synthesized and tested for their inhibitory activity against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide (3f), having a furan ring, was the most potent inhibitor of urease with an IC50 value of 0.58 ?M. Molecular modeling was carried out through docking the designed compounds into the urease binding site to predict whether these derivatives have analogous binding mode to the urease inhibitors. The study revealed that all of the tested compounds bind with both metal atoms at the active site of the enzyme. The aromatic ring of the compounds forms ionic interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637). PMID:24938644

  5. N-Substituted analogues of S-nitroso-N-acetyl-D,L-penicillamine: chemical stability and prolonged nitric oxide mediated vasodilatation in isolated rat femoral arteries.

    Science.gov (United States)

    Megson, I L; Morton, S; Greig, I R; Mazzei, F A; Field, R A; Butler, A R; Caron, G; Gasco, A; Fruttero, R; Webb, D J

    1999-02-01

    Previous studies show that linking acetylated glucosamine to S-nitroso-N-acetyl-D,L-penicillamine (SNAP) stabilizes the molecule and causes it to elicit unusually prolonged vasodilator effects in endothelium-denuded, isolated rat femoral arteries. Here we studied the propanoyl (SNPP; 3 carbon side-chain), valeryl (SNVP; 5C) and heptanoyl (SNHP; 7C) N-substituted analogues of SNAP (2C), to further investigate other molecular characteristics that might influence chemical stability and duration of vascular action of S-nitrosothiols. Spectrophotometric analysis revealed that SNVP was the most stable analogue in solution. Decomposition of all four compounds was accelerated by Cu(II) and cysteine, and neocuproine, a specific Cu(I) chelator, slowed decomposition of SNHP. Generation of NO from the compounds was confirmed by electrochemical detection at 37 degrees C. Bolus injections of SNAP (10 microl; 10(-8)-10(-3) M) into the perfusate of precontracted, isolated rat femoral arteries taken from adult male Wistar rats (400-500 g), caused concentration-dependent, transient vasodilatations irrespective of endothelial integrity. Equivalent vasodilatations induced by SNVP and SNHP were transient in endothelium-intact vessels but failed to recover to pre-injection pressures at moderate and high concentrations (10(-6)-10(-3) M) in those denuded of endothelium. This sustained effect (> 1 h) was most prevalent with SNHP and was largely reversed by the NO scavenger, haemoglobin. We suggest that increased lipophilicity of SNAP analogues with longer sidechains facilitates their retention by endothelium-denuded vessels; subsequent slow decomposition within the tissue generates sufficient NO to cause prolonged vasodilatation. This is a potentially useful characteristic for targeting NO delivery to areas of endothelial damage. PMID:10188974

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

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

    International Nuclear Information System (INIS)

    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)

  8. N-Aryl Lactams by Regioselective Ozonation of N-Aryl Cyclic Amines

    OpenAIRE

    Francesco Saliu; Marco Orlandi; Maurizio Bruschi

    2012-01-01

    Ozonation of N-aryl-cyclic amines in organic solvents gave N-aryl-lactams regioselectively. In particular, 4-(4-aminophenyl)-morpolin-3-one, a key intermediate in the preparation of factor Xa inhibitors, was obtained in fair yields. The method represents an alternative approach for the lactamization of tertiary N-arylic substrates and is based on a “metal-free” introduction of the carbonyl function into the heterocyclic ring.

  9. Palladium catalyzed diaryl sulfoxide generation from aryl benzyl sulfoxides and aryl chlorides.

    Science.gov (United States)

    Jia, Tiezheng; Zhang, Mengnan; Sagamanova, Irina K; Wang, Carol Y; Walsh, Patrick J

    2015-03-01

    Diaryl sulfoxides are synthesized from aryl benzyl sulfoxides and aryl chlorides via three sequential catalytic cycles all promoted by a NiXantPhos-based palladium catalyst. The key step is S-arylation of a sulfenate anion. An air- and moisture-stable precatalyst derived from NiXantPhos efficiently facilitates the transformation. Various functional groups, including those with acidic protons, were tolerated. This method can also be extended to methyl and dibenzyl sulfoxides substrates. PMID:25686150

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

    Scientific Electronic Library Online (English)

    Sara S. E., Ghodsinia; Batool, Akhlaghinia; Elham, Safaei; Hossein, Eshghi.

    2013-06-01

    Full Text Available N,N',N'',N'''-Tetrametil tetra(2,3-piridil)porfirazinato metil sulfato de cobre(II) ([Cu(2,3-tmtppa)](MeSO4)4) catalisou com sucesso a conversão direta de nitrilas a amidas N-substituídas. A síntese seletiva do tipo one pot de amidas N-substituídas a partir de nitrilas e aminas primárias foi realiza [...] da em refluxo de água. O catalisador foi recuperado e reusado no mínimo 4 vezes, mantendo a sua eficiência. Abstract in english N,N',N'',N'''-Tetramethyl tetra-2,3-pyridinoporphyrazinato copper(II) methyl sulfate ([Cu(2,3-tmtppa)](MeSO4)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 H2O. The catalyst was recovered and reused at least four times, maintaining its efficiency.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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 ?HfusT = 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.

  13. N-arylated-lactam-type iminosugars as new immunosuppressive agents: discovery, optimization, and biological evaluation.

    Science.gov (United States)

    Wu, Xiaowei; Zhang, Fu-Yu; Zhu, Jingjing; Song, Chengcheng; Xiong, De-Cai; Zhou, Yifa; Cui, Yuxin; Ye, Xin-Shan

    2014-08-01

    We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in?vitro and in?vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of 'hit' compound 12?f. Subsequently, the systematic modification of compound 12?f afforded compounds 21?h, 21?k, 21?n, 21?t, and 21?x with improved activities (IC50 =12-30??M) and low Jurkat cytotoxicities (IC50 >100??M). These new compounds also inhibited the secretion of IFN-? and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity. PMID:24700650

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

    Science.gov (United States)

    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

  15. Cavity ring-down spectroscopy of the 6?3 bands of 15N substituted N2O

    International Nuclear Information System (INIS)

    The 6?3 and ?2+6?3-?2 bands of 15N substituted nitrous oxide isotopologues have been recorded by a continuous-wave cavity ring-down spectrometer (CW-CRDS) operated near 0.8?m. The sensitivity limit was at the level of 1x10-10/cm. In total, 213, 86 and 191 transitions were observed for the 14N15N16O, 15N14N16O and 15N216O isotopologues, respectively. The ro-vibrational spectroscopic parameters of the upper states are determined from least square fitting of the transitions. The absolute line intensities of the 6?3 cold bands have been retrieved by a multi-line fitting procedure from the spectra with an estimated accuracy of 4% for majority of the unblended lines. The vibrational transition dipole moment squared values and the empirical Herman-Wallis coefficients are also presented.

  16. Targeting of Aryl Hydrocarbon Receptor-Mediated Activation of Cyclooxygenase-2 Expression by the Indole-3-Carbinol Metabolite 3,3?-Diindolylmethane in Breast Cancer Cells12

    OpenAIRE

    Degner, Stephanie C.; Papoutsis, Andreas J.; Selmin, Ornella; Romagnolo, Donato F.

    2009-01-01

    Ligands of the aryl hydrocarbon receptor (AhR) include the environmental xenobiotic 2,3,7,8 tetrachlorodibenzo(p)dioxin (TCDD), polycyclic aryl hydrocarbons, and the dietary compounds 3, 3?-diindolylmethane (DIM), a condensation product of indol-3-carbinol found in Brassica vegetables, and the phytoalexin resveratrol (RES). The AhR and its cofactors regulate the expression of target genes at pentameric (GCGTG) xenobiotic responsive elements (XRE). Because the activation of cyclooxygenase-2 ...

  17. Structure-activity relationships at monoamine transporters and muscarinic receptors for N-substituted-3alpha-(3'-chloro-, 4'-chloro-, and 4',4''-dichloro-substituted-diphenyl)methoxytropanes.

    Science.gov (United States)

    Newman, A H; Robarge, M J; Howard, I M; Wittkopp, S L; George, C; Kopajtic, T; Izenwasser, S; Katz, J L

    2001-02-15

    The design, synthesis, and evaluation of 3alpha-(diphenylmethoxy)tropane (benztropine) analogues have provided potent and selective probes for the dopamine transporter. Structure-activity relationships (SARs) have been developed that contrast with those described for cocaine, despite significant structural similarity. Furthermore, behavioral evaluation of many of the benztropine analogues in animal models of cocaine abuse has suggested that these two classes of tropane-based dopamine uptake inhibitors have distinct pharmacological profiles. In general, the benztropine analogues do not demonstrate efficacious locomotor stimulation in mice, do not fully substitute for a cocaine discriminative stimulus, and are not appreciably self-administered in rhesus monkeys. These compounds are generally more potent than cocaine as dopamine uptake inhibitors in vitro, although their actions in vivo are not consistent with this action. These observations suggest that differing binding profiles at the serotonin and norepinephrine transporters as well as at muscarinic receptors might have significant impact on the pharmacological actions of these compounds. In addition, by varying the structures of the parent compounds and thereby modifying their physical properties, pharmacokinetics as well as pharmacodynamics will be directly affected. Therefore, in an attempt to systematically evaluate the impact of chemical modification on these actions, a series of N-substituted (H, CH3, allyl, benzyl, propylphenyl, and butylphenyl) analogues of 3'-chloro-, 4'-chloro-, and 4,4''-dichloro-3alpha-(diphenylmethoxy)tropanes were synthesized. These compounds were evaluated for displacement, in rat tissue, of [3H]WIN 35,428 from the dopamine transporter, [3H]citalopram from the serotonin transporter, [3H]nisoxetine from the norepinephrine transporter, and [3H]pirenzepine from muscarinic m1 receptors. SARs were developed and compared to a series of N-substituted-3alpha-(bis-4'-fluorophenyl)methoxytropanes. The present SARs followed previously reported studies with the single exception of the N-butylphenyl substituent, which did not provide the high affinity binding in any of these three sets of analogues, as it did in the 4',4''-difluoro series. X-ray crystallographic analyses of the three parent ligands (1a, 2a, and 3a) were compared to that of 3alpha-(bis-4'-fluorophenyl)methoxytropane which provided supportive evidence toward the proposal that the combination of steric bulk in both the 3-position and the N-substituent, in this class of compounds, is not optimal for binding at the dopamine transporter. These studies provide binding profile data that can now be used to correlate with future behavioral analyses of these compounds and may provide insight into the kind of binding profile that might be targeted as a potential treatment for cocaine abuse. PMID:11170654

  18. The Remarkable Reactivity of Aryl Halides with Nucleophiles

    Science.gov (United States)

    Bunnett, Joseph F.

    1974-01-01

    Discusses the reactivity of aryl halides with nucleophilic or basic reagents, including nucleophilic attacks on carbon, hydrogen, halogen, and arynes. Suggestions are made concerning revisions of the sections on aryl halide chemistry courses and the corresponding chapters in textbooks. (CC)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Transition-metal-free highly chemo- and regioselective arylation of unactivated arenes with aryl halides over recyclable heterogeneous catalysts.

    Science.gov (United States)

    Liu, Hongli; Yin, Biaolin; Gao, Zhiqiang; Li, Yingwei; Jiang, Huanfeng

    2012-02-14

    A novel heterogeneous catalysis system using metal-organic frameworks as catalyst demonstrated excellent chemo- and regioselectivity for the direct arylation of unactivated arenes with aryl iodides/bromides without the assistance of any transition metals. PMID:22227601

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

    Science.gov (United States)

    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)

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Synthesis of functionalized pseudopeptides through five-component sequential Ugi/nucleophilic reaction of N-substituted 2-alkynamides with hydrazides.

    Science.gov (United States)

    Maghari, Shokoofeh; Ramezanpour, Sorour; Balalaie, Saeed; Darvish, Fatemeh; Rominger, Frank; Bijanzadeh, Hamid Reza

    2013-07-01

    Five-component sequential Ugi/nucleophilic addition reaction of aromatic aldehydes, primary amines, propiolic acid, isocyanides, and hydrazides has been developed in order to access polyfunctional pseudopeptides. The reaction may proceed through formation of N-substituted 2-alkynamides as intermediates. This process is found to be mild and operationally simple with broad substrate scope. PMID:23734677

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

    Science.gov (United States)

    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. Synthesis and antibacterial activity of some novel 2-Aroylimino-3-aryl-thiazolidin-4-ones

    Scientific Electronic Library Online (English)

    Aamer, Saeed; Naeem, Abbas; Ulrich, Flörke.

    Full Text Available SciELO Brazil | Language: English Abstract in portuguese Este trabalho relata uma síntese eficiente e regio-seletiva de algumas 2-aroylimino-3-aryl-thiazolidin-4-ones (2a-j) envolvendo a ciclização de 1-aroyl-3-aryl tio-uréias em meio básico com cloreto de cloroacetila em dioxana. As estruturas foram confirmadas por dados espectroscópicos, análises elemen [...] tares e, em um caso (2j), por dados de difração de raios X tipo cristal único. Os compostos foram testados in vitro quanto à sua atividade antimicrobiana em relação a bactérias Gram positivas e Gram negativas. Os resultados revelaram uma atividade promissora desses compostos em relação aos microorganismos testados, comparando-se e, em alguns casos, até superando a atividade das drogas existentes. Abstract in english An efficient, regioselective synthesis of some 2-aroylimino-3-aryl-thiazolidin-4-ones (2a-j) involving base-catalyzed cyclization of 1-aroyl-3-aryl thioureas with chloroacetyl chloride in dioxane is reported. The structures were confirmed by spectroscopic data, elemental analyses and in one case (2j [...] ) by single crystal X-ray diffraction data. Compounds (2a-j) were assayed in vitro for their antimicrobial activity against Gram positive and Gram negative bacteria and were found to exhibit promising activity towards the tested microorganisms, comparable to and in some cases better than those of the standard drugs.

  6. REDUCTION OF VITELLOGENIN SYNTHESIS BY AN ARYL HYDROCARBON RECEPTOR AGONIST IN THE WHITE STURGEON (ACIPENSER TRANSMONTAMUS)

    OpenAIRE

    Palumbo, Amanda J.; Denison, Michael S.; Doroshov, Serge I.; Tjeerdema, Ronald S.

    2009-01-01

    Migrating white sturgeon (Acipenser transmontamus) may be subject to agricultural, municipal, and industrial wastewater effluents that likely contain different classes of endocrine-disrupting contaminants. Concern is mounting about the negative effects of environmental estrogens on fish reproduction; however, in environmental mixtures, the affects from estrogenic compounds may be suppressed by aryl hydrocarbon receptor (AhR) ligands. Indeed, reductions in 17?-estradiol–induced (0.01 and 1 ...

  7. Diaryliodonium Salts : Development of Synthetic Methodologies and ?-Arylation of Enolates

    OpenAIRE

    Bielawski, Marcin

    2011-01-01

    This thesis describes novel reaction protocols for the synthesis of diaryliodonium salts and also provides an insight to the mechanism of ?-arylation of carbonyl compounds with diaryliodonium salts.  The first chapter gives a general introduction to the field of hypervalent iodine chemistry, mainly focusing on recent developments and applications of diaryliodonium salts. Chapter two describes the synthesis of electron-rich to electron-poor diaryliodonium triflates, in moderate to excellent ...

  8. Photochemistry of fluorinated aryl azides in toluene solution and in frozen polycrystals

    Energy Technology Data Exchange (ETDEWEB)

    Leyva, E.; Munoz, D.; Platz, M.S. (Ohio State Univ., Columbus (USA))

    1989-12-08

    Several fluorinated triplet aryl nitrenes have been generated in low-temperature polycrystals by photolysis of the corresponding azides. Upon extended photolysis at {minus}196{degree}C the nitrenes abstract hydrogen from frozen toluene to give anilino-benzyl radical pairs, which subsequently combine to give CH insertion products. The radical pairs and the triplet nitrenes have been detected by EPR. In toluene solution, the major reaction products are tar, the corresponding fluorinated anilines, and azo compounds.

  9. PMR spectra and conformations of the cis and trans isomers of N-substituted 2,5-dimethyl-4-piperidones

    International Nuclear Information System (INIS)

    The PMR spectra of mixtures of the trans and cis isomers of N-substituted 2,5-dimethyl-4-piperidones with three N-substituents (H, CH3, and CH2C6H5) and the hydrobromide of trans-2,5-dimethyl-4-piperidone were investigated at 250 and 360 MHz. The spectra of the major trans isomers were analyzed fully for the first time, and the relation between their PMR parameters and the stereochemical structure was investigated. It was shown that these isomers are predominantly represented by the 1e, 2e, and 5e conformations in the chair form of the piperidine ring. As a result of analysis of the PMR spectra of the minor cis isomers it was established that they are conformationally nonuniform and are characterized by a conformational equilibrium between the two chair forms Cl (1a, 2e, 5a) and C2 (1a, 2a, 5e), which is displaced toward C2 with increase in the size of the N-substituent. The populations and the differences in the energies were determined for these conformers

  10. N-substituted monodentate alcohols as ligands modifying structure, properties and thermal stability of Mo(IV) complexes

    Science.gov (United States)

    Jurowska, Anna; Szklarzewicz, Janusz; Hodorowicz, Maciej; Tomecka, Monika; Lipkowski, Janusz; Nitek, Wojciech

    2015-02-01

    The reaction of N-substituted alcohols (2-aminoethanol, 3-amino-1-propanol and 2-hydroxyethylhydrazine) with K3Na[Mo(CN)4O2]?6H2O in water-ethanol solution results in isolation of three new complexes of formulae: (PPh4)2[Mo(CN)4O(amet)]?3H2O (1), (amet = 2-aminoethanol), (PPh4)2[Mo(CN)4O(ampro)]?3H2O (2) (ampro = 3-amino-1-propanol) and (PPh4)2[Mo(CN)4O(ethyd)]?3H2O (3) (ethyd = 2-hydroxyethylhydrazine). The isolated salts were characterized by elemental analysis, single crystal X-ray structure measurements, IR and UV-Vis spectroscopy and cyclic voltammetry. The complexes crystalize in triclinic space group with distorted octahedral geometry of the anion. The obtained salts belongs to a very rare group of complexes with monodentate terminal N-donating alcohols. The thermal stability is described for all complexes and compared with crystal structure parameters.

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

    International Nuclear Information System (INIS)

    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 applied–ve 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 applied–ve field and to release the metal ion on stepping the potential to zero

  12. Catalytic asymmetric synthesis of sterically hindered tertiary ?-aryl ketones.

    Science.gov (United States)

    Doran, Robert; Guiry, Patrick J

    2014-10-01

    The catalytic asymmetric synthesis of a series of tertiary ?-aryl cyclopentanones and cyclohexanones has been accomplished via a Pd-catalyzed decarboxylative protonation of the corresponding ?-aryl-?-keto allyl esters. Enantioselectivities of up to 92% ee and 74% ee were achieved for cyclopentanone and cyclohexanone substrates, respectively. The route described gives access to these important structural motifs in moderate to high levels of enantioselectivity. In particular, this is only the second direct approach for the preparation of tertiary ?-aryl cyclopentanones. The synthetic approach allows for simple modification of the aryl group. Significantly, substrates containing sterically hindered aryl groups gave the highest levels of enantioselectivity, and these aryl groups were readily installed by a Pb-mediated arylation of a ?-keto allyl ester. PMID:25233274

  13. Radiolabeled n-substituted-6-iodo-3, 14-dihydroxy-4, 5alpha-epoxymorphinans, intermediates for producing the same, and a process for the preparation and methods of detecting opioid receptors

    International Nuclear Information System (INIS)

    The invention is directed to radiolabeled N-substituted-6-iodo-3,14-dihydroxy-4,5 alpha-epoxymorphinans, intermediates for producing the same, and a process for the preparation and methods of detecting opioid receptors, wherein Iodo is selected from the group consisting of (123)I and (125)I; and where the N substitution is alkyl, cycloalkylloweralkyl or allyl

  14. Radiolabeled n-substituted-6-iodo-3, 14-dihydroxy-4, 5alpha-epoxymorphinans, intermediates for producing the same, and a process for the preparation and methods of detecting opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    de Costa, B.R.; Iadarola, M.J.; Rothman, R.B.; Berman, K.F.; Rice, K.C.

    1991-01-01

    The invention is directed to radiolabeled N-substituted-6-iodo-3,14-dihydroxy-4,5 alpha-epoxymorphinans, intermediates for producing the same, and a process for the preparation and methods of detecting opioid receptors, wherein Iodo is selected from the group consisting of (123)I and (125)I; and where the N substitution is alkyl, cycloalkylloweralkyl or allyl.

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

    International Nuclear Information System (INIS)

    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+-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.

  16. Cloning and sequencing of the gene for a Pseudomonas paucimobilis enzyme that cleaves beta-aryl ether.

    OpenAIRE

    Masai, E.; Katayama, Y.; Kawai, S.; Nishikawa, S.; Yamasaki, M.; Morohoshi, N.

    1991-01-01

    We isolated Pseudomonas paucimobilis SYK-6, which was able to degrade various dimeric lignin compounds (Y. Katayama, S. Nishikawa, M. Nakamura, K. Yano, M. Yamasaki, N. Morohoshi, and T. Haraguchi, Mokuzai Gakkaishi 33:77-79, 1987). This metabolic process is a distinct characteristic of this bacterium, which is equipped with an enzymatic modification system for various dimeric lignin compounds involved in the tricarboxylic acid cycle. Cleavage of the beta-aryl ether linkage is essential in th...

  17. PCB 126 and Other Dioxin-Like PCBs Specifically Suppress Hepatic PEPCK Expression via the Aryl Hydrocarbon Receptor

    OpenAIRE

    Zhang, Wenshuo; Sargis, Robert M.; Volden, Paul A.; Carmean, Christopher M.; Sun, Xiao J.; Brady, Matthew J.

    2012-01-01

    Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs), however, commenced early in the 20th century and continued for decades; dioxin-like ...

  18. Synthesis and pharmacological evaluation of a novel series of 3-aryl-2-(2-substituted-4-methylthiazole-5-yl)thiazolidin-4-one as possible anti-inflammatory and antimicrobial agents.

    Science.gov (United States)

    Shelke, Shivaji H; Mhaske, Pravin C; Nandave, Mukesh; Narkhade, Sachin; Walhekar, Namdeo M; Bobade, Vivek D

    2012-10-15

    A new series of 3-aryl-2-(2-aryl/benzyl-4-methylthiazole-5-yl)thiazolidin-4-one was synthesized by condensation of 2-aryl/benzyl-4-methylthiazole-5-carbaldehyde, aromatic amines and thioglycolic acid in toluene. All the synthesized compounds are characterized by IR, NMR and elemental or mass analysis. Sixteen out of the newly synthesized compounds were screened for in vivo anti-inflammatory activity using carrageenan-induced rat paw edema method. Some of the synthesized compounds exhibited good anti-inflammatory activity compared with indomethacin. The synthesized compounds were also evaluated for their in vitro antimicrobial activity. Some of the compounds showed mild antibacterial activity while most of the compounds showed good antifungal activity. PMID:22981329

  19. Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides.

    Science.gov (United States)

    Ahmad, Matloob; Aslam, Sana; Rizvi, Syed Umar Farooq; Muddassar, Muhammad; Ashfaq, Usman Ali; Montero, Catherine; Ollinger, Olivia; Detorio, Mervi; Gardiner, John M; Schinazi, Raymond F

    2015-03-15

    Two series of fifteen N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides were screened for anti-HIV-1 activity and cytotoxicity. The compounds 6a, 6d, 6e, 6g and 6i from the series 6a-i of benzylamides and 7a, 7b, 7c, 7d and 7e from the series 7a-f of anilides were identified as effective anti-HIV-1 agents with EC50 values cells, with the exception of 6a which displayed toxicity in Vero cells. Molecular docking of these compounds provided insight into the molecular mechanism and it was found that 6e, 6g and 6i bound deeply in the NNRTI binding pocket of the HIV-1 reverse transcriptase, using RT-bound nevirapine X-ray data and molecular docking for validation, showing the potential of these new structures as inhibitors of this viral enzyme. PMID:25701249

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

    International Nuclear Information System (INIS)

    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)

  1. Synthesis and Bronchodilator Studies of Some Novel 6-Alkyl/Aryl-1,2,4-Triazino[4,3-c]Quinazolines

    OpenAIRE

    Kombu, Rajan Subramanian; Mailavaram, Raghu Prasad; Devalapally, Harikrishna; Chinnappa, Prabhakar Marsanapalli; Devarakonda, Rama Krishna; Akkinepally, Raghu Ram Rao

    2008-01-01

    A series of alkyl- and aryl-1,2,4-triazino[4,3-c]quinazolines (5a-h and 8a-h) were synthesized and characterized. The title compounds were evaluated for their in vivo bronchodilator activity on guinea pigs. All the test compounds exhibited good protection against histamine-induced bronchospasm. The structure-activity relationships based on the results obtained for these series were studied. Incorporation of an aryl ring with halo substitution to the theophylline bioisostere increases its pote...

  2. Design, synthesis and anti-tobacco mosaic virus (TMV) activity of 5-chloro-N-(4-cyano-1-aryl-1H-pyrazol-5-yl)-1-aryl-3-methyl-1H-pyrazole-4-carboxamide derivatives.

    Science.gov (United States)

    Xiao, Jin-Jing; Liao, Min; Chu, Ming-Jie; Ren, Zi-Li; Zhang, Xin; Lv, Xian-Hai; Cao, Hai-Qun

    2015-01-01

    A series of novel pyrazole amide derivatives 3a-3p which take TMV PC protein as the target has been designed and synthesized by the reactions of 5-chloro-1-aryl-3-methyl-1H-pyrazole-4-carboxylic acids with 5-amino-1-aryl-1H-pyrazole-4-carbonitriles. All the compounds were characterized by 1H-NMR, mass spectroscopy and elemental analysis. Preliminary bioassays indicated that all the compounds acted against the tobacco mosaic virus (TMV) with different in vivo and in vitro modes at 500 ?g/mL and were found to possess promising activity. Especially, compound 3p showed the most potent biological activity against tobacco mosaic virus (TMV) compared to ningnanmycin, and a molecular docking study was performed and the binding model revealed that the pyrazole amide moiety was tightly embedded in the binding sites of TMV PC (PDB code: 2OM3). PMID:25574822

  3. Design, Synthesis and Anti-Tobacco Mosaic Virus (TMV Activity of 5-Chloro-N-(4-cyano-1-aryl-1H-pyrazol-5-yl-1-aryl-3-methyl-1H-pyrazole-4-carboxamide Derivatives

    Directory of Open Access Journals (Sweden)

    Jin-Jing Xiao

    2015-01-01

    Full Text Available A series of novel pyrazole amide derivatives 3a–3p which take TMV PC protein as the target has been designed and synthesized by the reactions of 5-chloro-1-aryl-3-methyl-1H-pyrazole-4-carboxylic acids with 5-amino-1-aryl-1H-pyrazole-4-carbonitriles. All the compounds were characterized by 1H-NMR, mass spectroscopy and elemental analysis. Preliminary bioassays indicated that all the compounds acted against the tobacco mosaic virus (TMV with different in vivo and in vitro modes at 500 ?g/mL and were found to possess promising activity. Especially, compound 3p showed the most potent biological activity against tobacco mosaic virus (TMV compared to ningnanmycin, and a molecular docking study was performed and the binding model revealed that the pyrazole amide moiety was tightly embedded in the binding sites of TMV PC (PDB code: 2OM3.

  4. Palladium-Catalyzed Reactions of Arylindium Reagents Prepared Directly from Aryl Iodides and Indium Metal

    Science.gov (United States)

    Papoian, Vardan

    2008-01-01

    Treatment of aryl iodides with indium metal in the presence of lithium chloride leads to the formation of an organoindium reagent capable of participating in cross-coupling reactions under transition-metal catalysis. Combination with aryl halides in the presence of 5 mol% Cl2Pd(dppf) furnishes biaryl compounds in good yields; similarly, reaction with acyl halides or allylic acetates/carbonates in the presence of 5–10 mol % palladium catalyst leads to arylketones and allylic substitution products, respectively, in moderate yields. The reactions are tolerant of the presence of protic solvents, and ~85% of the indium metal employed can be recovered by reduction of the residual indium salts with zinc(0). PMID:18722408

  5. Direct arylation of N-heteroarenes with aryldiazonium salts by photoredox catalysis in water.

    Science.gov (United States)

    Xue, Dong; Jia, Zhi-Hui; Zhao, Cong-Jun; Zhang, Yan-Yan; Wang, Chao; Xiao, Jianliang

    2014-03-01

    A highly effective visible light-promoted "radical-type" coupling of N-heteroarenes with aryldiazonium salts in water has been developed. The reaction proceeds at room temperature with [Ru(bpy)3 ]Cl2 ?6?H2 O as a photosensitizer and a commercial household light bulb as a light source. Pyridine and a variety of substituted pyridines are effective substrates under these reaction conditions, and only monosubstituted products are formed with different regioselectivities. Using aqueous formic acid as solvent, an array of xanthenes, thiazole, pyrazine, and pyridazine are compatible with this new arylation approach. The broad substrate scope, mild reaction conditions, and use of water as reaction solvent make this procedure a practical and environmentally friendly method for the synthesis of compounds containing aryl-heteroaryl motifs. PMID:24500947

  6. Synthesis of N-Substituted-2-Aminothiazolo[4,5-b]pyrazines by Tandem Reaction of o-Aminohalopyrazines with Isothiocyanates

    International Nuclear Information System (INIS)

    In conclusion, a convenient and mild method for the synthesis of N-substituted-2-aminothiazolo[4,5-b]pyrazines, which might either exhibit potential pharmacological activities or be used as building blocks, via tandem reactions of various pyrazines and isothiocyanates has been developed. All substrates were well converted to the desired products. The generality of this reaction could enable its application to other substrates

  7. PALLADIUM CATALYZED COUPLING OF ARYL HALIDES WITH ARYLHALOSILANES IN AIR AND WATER. (R828129)

    Science.gov (United States)

    In the presence of a palladium catalyst, various aryl halides reacted with arylhalosilanes in aqueous media and under an air atmosphere to give the corresponding unsymmetrical aryl–aryl coupling products conveniently. ...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Palladium-Catalyzed alpha-Arylation of Tetramic Acids

    DEFF Research Database (Denmark)

    Storgaard, Morten; Dorwald, F. Z.

    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 K2CO3 or K3PO4, and aryl chlorides, bromides, or triflates in THF. With conventional heating, conversions >95% could be attained after 1 h at 80 degrees C, whereas microwave-induced heating led to much shorter reaction times (5 min at 110 degrees C). The electron density of the aryl electrophile had no effect on their reactivity: both electron-rich and electron-poor aryl chlorides and bromides or triflates led to good yields. Ortho-substituted aryl halides and heteroaryl halides, however, did not undergo the title reaction.

  10. Catalytic SNAr of unactivated aryl chlorides.

    Science.gov (United States)

    Walton, James W; Williams, Jonathan M J

    2015-02-18

    We present nucleophilic aromatic substitution of unsubstituted aryl chlorides via a mechanism that is catalytic in [CpRu(p-cymene)]PF6 and involves a Ru(?(6)-arylchloride) intermediate. From the spectroscopic evidence we infer that arene exchange is the rate limiting step in this process and develop several new Ru(ii) complexes that lower the activation barrier to arene exchange. PMID:25300517

  11. Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp(3) C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems.

    Science.gov (United States)

    Parella, Ramarao; Babu, Srinivasarao Arulananda

    2015-02-20

    An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp(3) C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp(3))-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities. The stereochemistry of the products obtained in this work were unambiguously assigned on the basis of the X-ray structure analyses of representative compounds 3b, 3e, 4p, and 7. PMID:25588549

  12. N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

    Directory of Open Access Journals (Sweden)

    Ismail Özdemir

    2013-02-01

    Full Text Available New Pd–NHC 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.

  13. Microbial biotransformation of aryl sulfanylpentafluorides.

    Science.gov (United States)

    Kavanagh, Emma; Winn, Michael; Gabhann, Cliona Nic; O'Connor, Neil K; Beier, Petr; Murphy, Cormac D

    2014-01-01

    We report, for the first time, the biotransformation of potential pollutants bearing the pentafluorosulfanyl (SF5-) functional group in a fungus and bacteria. Cunninghamella elegans transformed p-methoxy phenyl SF5 via demethylation; Pseudomonas knackmussii and P. pseudoalcaligenes KF707 transformed amino-, hydroxyamino- and diamino- substituted phenyl SF5, forming the N-acetylated derivatives as the main product. Cell-free extract of Streptomyces griseus transformed 4-amino-3-hydroxy-phenyl SF5 to the N-acetylated derivative in the presence of acetyl CoA, confirming that an N-acetyltransferase is responsible for the bacterial biotransformations. Approximately 25% of drugs and 30% of agrochemicals contain fluorine, and the trifluoromethyl group is a prominent feature of many of these since it improves lipophilicity and stability. The pentafluorosulfanyl substituent is seen as an improvement on the trifluoromethyl group and research efforts are underway to develop synthetic methods to incorporate this moiety into biologically active compounds. It is important to determine the potential environmental impact of these compounds, including the potential biotransformation reactions that may occur when they are exposed to microorganisms. PMID:23872898

  14. Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

    OpenAIRE

    Jin, Rongwei; Bheeter, Charles Beromeo; Doucet, Henri

    2014-01-01

    The use of the congested aryl bromide 2-bromo-1,3-dichlorobenzene as coupling partner allows to modify the regioselectivity of the arylation of 3-substituted thiophene derivatives in favour of carbon C5. The coupling of this aryl bromide with a variety of 3-substituted thiophenes gave in all cases the desired 5-arylation products in moderate to good yields using only 0.5 mol % of a phosphine-free and air-stable palladium catalyst. Then, from these 5-arylthiophenes, a second palladium-catalyse...

  15. Synthesis and biological activity of N-substituted aminocarbonyl-1,3-dioxolanes as VLA-4 antagonists.

    Science.gov (United States)

    Rehman, Abdul; Soni, Ajay; Naik, Keshav; Nair, Sreeji; Palle, Venkata P; Dastidar, Sunanda; Ray, Abhijit; Alam, M S; Salman, Mohammad; Cliffe, Ian A; Sattigeri, Viswajanani

    2010-09-15

    A novel set of compounds with a 1,3-dioxolane ring which acts as a proline bioisostere have been successfully designed as VLA-4 receptor antagonists. Compounds (18e), (28j), and (35g) were shown to have high receptor affinities. PMID:20705461

  16. 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

    Directory of Open Access Journals (Sweden)

    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.

  17. Anticonvulsant Profiles of Certain New 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones

    Directory of Open Access Journals (Sweden)

    Mohamed N. Aboul-Enein

    2014-09-01

    Full Text Available Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a–l and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (6m–x are reported. The intermediates 1-[(aryl(cyanomethylamino] cycloalkanecarboxamides (3a–f were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent N-cyanomethylation. Compounds 3a–f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives 4a–f which were cyclized under mild conditions to give the spiro compounds 5a–f. Ultimately, compounds 5a–f were alkylated or aralkylated to give the target compounds 6a–i and 6m–u. On the other hand, compounds 6j–l and 6v–x were synthesized from the intermediates 5a–f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds 6a–x revealed that compound 6g showed an ED50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED50 = 0.06 mmol/kg and Ethosuximide (ED50 = 0.92 mmol/kg, respectively. Compound 6e exhibited an ED50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED50 = 0.034 mmol/kg in the MES screen. Interestingly, all the test compounds 6a–x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Synthesis, half-wave potentials and antiproliferative activity of 1-aryl-substituted aminoisoquinolinequinones.

    Science.gov (United States)

    Ibacache, Juana Andrea; Delgado, Virginia; Benites, Julio; Theoduloz, Cristina; Arancibia, Verónica; Muccioli, Giulio G; Valderrama, Jaime A

    2013-01-01

    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). PMID:24406784

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

    International Nuclear Information System (INIS)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Thomas J. J. Müller

    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.

  4. Combined effects of one 8-hydroxyquinoline/picolinate and "CH"/N substitutions on the geometry, electronic structure and optical properties of mer-Alq(3).

    Science.gov (United States)

    Gahungu, Godefroid; Zhang, Jingping; Ntakarutimana, Vestine; Gahungu, Nestor

    2010-01-14

    With the aim of evaluating the combined effect of one 8-hydroxyquinoline (q)/picolinate (p) and "CH"/N substitutions on the molecular geometry, electronic structure, and optical properties of tris-(8-hydroxyquinoline)aluminum [Alq(3)], the density functional theory (B3LYP) and time-dependent density functional theory (TD-B3LYP), using the 6-31G(d) and 3-21+G(d,p) basis sets were applied on Alq(3), Alq(2)p, and its "CH"/N-substitution derivatives. A comparison of the optimized ground-state (S(0)) geometries has shown that the molecular shape is conserved upon such a substitution. On the basis of the frontier molecular orbital and gap energy (E(g)) calculations, it was shown that, comparatively to the pristine Alq(2)p (and to the original parent Alq(3)), the HOMO and LUMO are stabilized, the net effect being an increasing or a decreasing E(g), depending on the position of the substituted group. The substitution of q(B) by p (from Alq(3) to Alq(2)p) was also found to induce the same feature. Starting from the S(0) and S(1) (first excited state) geometries, the effect of the substitution on the absorption (and emission) spectra was evaluated. It was found that the "CH"/N substitution in different positions on the two 8-hydroxyquinoline ligands may also constitute an efficient approach of tuning the Alq(2)p emitting color. In comparison with both Alq(3) and Alq(2)p, an important blue shift was predicted for the 5-substituted derivative, an important red shift being observed for the 4-substituted one. Also, relatively significant blue and red shifts were predicted for the 7- and 2-substituted derivatives. Finally, revisiting the correlation between the spectrum shifts and the metal-ligand bonding, our recent findings (2) were confirmed. PMID:19904976

  5. N-substituted 2-aminobiphenylpalladium methanesulfonate precatalysts and their use in C-C and C-N cross-couplings.

    Science.gov (United States)

    Bruno, Nicholas C; Niljianskul, Nootaree; Buchwald, Stephen L

    2014-05-01

    A series of phosphine-ligated palladium precatalysts based on N-methyl- and N-phenyl-2-aminobiphenyl have been developed. Substitution at the nitrogen center prevents the presence of traces of aminobiphenyls that contain a free -NH2 group from contaminating cross-coupling products. These precatalysts produce N-substituted carbazoles upon activation, which cannot consume starting materials. These precatalysts were efficiently generated from 2-aminobiphenyl with minimal purification and found to be highly effective in Suzuki-Miyaura and C-N cross-coupling reactions. PMID:24724692

  6. C- versus O-Arylation of an Enol-Lactone Using Potassium tert-butoxide

    Directory of Open Access Journals (Sweden)

    El Moktar Essassi

    2003-05-01

    Full Text Available Abstract: The use of potassium tert-butoxide as the base in arylation reactions of an enollactone with a series of benzyl halides was explored. Our work demonstrates that the ratio of C-arylation to O-arylation varies with the substitution pattern of the aryl halide.

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

    Directory of Open Access Journals (Sweden)

    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 ?M compared to that of NADPH (39 ?M. 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.

  8. Synthesis and fluorescence properties of N-substituted 1-cyanobenz[f]isoindole chitosan polymers and nanoparticles for live cell imaging.

    Science.gov (United States)

    Gonil, Pattarapond; Sajomsang, Warayuth; Ruktanonchai, Uracha Rungsardthong; Na Ubol, Preeyawis; Treetong, Alongkot; Opanasopit, Praneet; Puttipipatkhachorn, Satit

    2014-08-11

    Highly fluorescent N-substituted 1-cyanobenz[f]isoindole chitosans (CBI-CSs) with various degrees of N-substitution (DS) were synthesized by reacting chitosan (CS) with naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide under mild acidic conditions. Introduction of 1-cyanobenz[f]isoindole moieties into the CS backbone resulted in lowering of polymer thermal stability and crystallinity. The fluorescence quantum yield (?f) of CBI-CS was found to be DS- and molecular-weight-dependent, with ?f decreasing as DS and molecular weight were increased. At similar DS values, CBI-CS exhibited 26 times higher ?f in comparison with fluorescein isothiocyanate-substituted chitosan (FITC-CS). CBI-CS/TPP nanoparticles were fabricated using an ionotropic gelation method in which pentasodium triphosphate (TPP) acted as a cross-linking agent. CS and CBI-CS exhibited low cytotoxicity to normal skin fibroblast cells over a concentration range of 0.1-1000 ?g/mL, while an increased cytotoxicity level was evident in CBI-CS/TPP nanoparticles at concentrations greater than 100 ?g/mL. In contrast with CBI-CS polymers, the CBI-CS/TPP nanoparticles exhibited lower fluorescence; however, confocal microscopy results showed that living normal skin fibroblast cells became fluorescent on nanoparticle uptake. These results suggest that CBI-CS and fabricated nanoparticles thereof may be promising fluorescence probes for live cell imaging. PMID:24956200

  9. "CH"/N substituted mer-Gaq3 and mer-Alq3 derivatives: an effective approach for the tuning of emitting color.

    Science.gov (United States)

    Gahungu, Godefroid; Zhang, Jingping

    2005-09-22

    Equilibrium geometry configurations of the "CH"/N substituted Alq3 and Gaq3 derivatives are calculated by density functional theory (B3LYP/6-31G). The frontier molecular orbital and gap energy calculations for all complexes have been performed at the HF/6-31G level. It was shown that, compared to the pristine molecules, the HOMO and LUMO are stabilized, the net effect being however an increasing/decreasing of the gap (Eg) depending on the position of the substituted group. On the basis of the equilibrium geometries, the effect of the substitution on the absorption and emission spectra was evaluated using TDB3LYP/3-21G. It was shown that the change of "CH"/N substituted position on 8-hydroxyquinoline ligand is a powerful approach for the tuning of emitting color. An important blue shift was predicted for 5-substituted 8-hydroxyquinoline derivatives, an important red one being observed for 4-substituted ones. Interestingly, relatively significant blue and red shifts were also predicted for the 7- and 2-substituted derivatives. In this work, the correlation between the spectrum shifts and the metal-ligand bonding is also discussed. PMID:16853272

  10. Novel 1-(2-aryl-2-adamantyl)piperazine derivatives with antiproliferative activity.

    Science.gov (United States)

    Fytas, Christos; Zoidis, Grigoris; Tsotinis, Andrew; Fytas, George; Khan, Mohsin A; Akhtar, Samar; Rahman, Khondaker M; Thurston, David E

    2015-03-26

    Novel 1-(2-aryl-2-adamantyl)piperazine derivatives have been synthesized and evaluated in vitro for their antitumor properties against HeLa cervical carcinoma, MDA MB 231 breast cancer, MIA PaCa2 pancreatic cancer, and NCI H1975 non-small cell lung cancer. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 ??, respectively). Concurrent benzene ring C4-fluorination and piperidine acetylation of the piperazino NH of compound 6 resulted in the most active compound 13 of the series in both of the above cell lines (IC50=8.4 and 6.8 ??, respectively). Noticeably, compounds 6 and 13 exhibited a significantly low cytotoxicity level over the normal human cells HUVEC (Human Umbilical Vein Endothelial Cells) and NHDF (Normal Human Dermal Fibroblasts). PMID:25703296

  11. Synthesis Of [2h, 13c]M [2h2m 13c], And [2h3,, 13c] Methyl Aryl Sulfones And Sulfoxides

    Science.gov (United States)

    Martinez, Rodolfo A. (Santa Fe, NM); Alvarez, Marc A. (Santa Fe, NM); Silks, III, Louis A. (Los Alamos, NM); Unkefer, Clifford J. (Los Alamos, NM); Schmidt, Jurgen G. (Los Alamos, NM)

    2004-07-20

    The present invention is directed to labeled compounds, [.sup.2 H.sub.1, .sup.13 C], [.sup.2 H.sub.2, .sup.13 C] and [.sup.2 H.sub.3, .sup.13 C]methyl aryl sulfones and [.sup.2 H.sub.1, .sup.13 C], [.sup.2 H.sub.2, .sup.13 C] and [.sup.2 H.sub.3, .sup.13 C]methyl aryl sulfoxides, wherein the .sup.13 C methyl group attached to the sulfur of the sulfone or sulfoxide includes exactly one, two or three deuterium atoms and the aryl group is selected from the group consisting of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently, hydrogen, a C.sub.1 -C.sub.4 lower alkyl, a halogen, an amino group from the group consisting of NH.sub.2, NHR and NRR' where R and R' are each a C.sub.1 -C.sub.4 lower alkyl, a phenyl, or an alkoxy group. The present invention is also directed to processes of preparing methyl aryl sulfones and methyl aryl sulfoxides.

  12. The Barbier-Grignard-type arylation of aldehydes using unactivated aryl iodides in water.

    Science.gov (United States)

    Zhou, Feng; Li, Chao-Jun

    2014-01-01

    Carbon-carbon bond formation is the essence of organic synthesis. One of the most important methods for forming carbon-carbon bonds is the Barbier-Grignard-type reaction, which was discovered over a century ago. However, it is still highly desirable to further improve this process. In this article, we describe a Barbier-Grignard-type direct arylation of aldehydes by using unactivated iodides mediated by zinc and catalysed by rhodium in water. This method bypasses a number of challenges encountered by the conventional Barbier-Grignard reaction, such as strict exclusion of moisture and air, protection-deprotection of various acidic hydrogens in the substrates, and so forth. It thereby creates a safer, more convenient and more environmentally benign strategy to access the diarylmethanols and aryl alkyl alcohols, ubiquitous skeletons found in fine chemicals, biologically active molecules and pharmaceuticals. Importantly, the same reaction performed in an organic solvent proceeded sluggishly to give much inferior yields. PMID:24968128

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

  14. Selective copper catalysed aromatic N-arylation in water

    DEFF Research Database (Denmark)

    Engel-Andreasen, Jens; Shimpukade, Bharat

    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 the possibility for low metal and ligand loadings give the process a benign environmental profile. [on SciFinder(R)

  15. Effect of substituents on the 13C chemical shifts of the azomethine carbon atom of N-(substituted phenylmethylene)-3- and -4-aminobenzoic acids

    Science.gov (United States)

    Jovanovi?, B. Ž.; Marinkovi?, A. D.; Assaleh, F. H.; Csanádi, J.

    2005-06-01

    13C chemical shifts of the azomethine carbon atom for N-(substituted phenylmethylene)-3- and -4-aminobenzoic acids having a wide range of substituent effects, were determined in deuterated DMSO solution. Good Hammett correlations of the 13C NMR chemical shifts of azomethine carbons with electrophilic substituent constants ?p+ for electron-donor substituents for both series of acids indicate an important resonance interaction of the substituents on the benzylidene ring with the azomethine carbon atom. On the other hand, good correlations of the 13C NMR chemical shifts of azomethine carbon atom of both series of acids with inductive substituent constants for electron-acceptor substituents in benzylidene ring indicates that the chemical shifts are influenced only by inductive effect of the substituents. The demand for electrons by the azomethine carbon atom in both investigated series have been compared, discussing the mode of transmission of substituent effects, both inductive and resonance, in relation to the geometry of investigated imines.

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

    Directory of Open Access Journals (Sweden)

    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. Aryl chain analogues of the biotin vitamers as potential herbicides. Part 3.

    Science.gov (United States)

    Ashkenazi, Tali; Pinkert, Dalia; Nudelman, Ayelet; Widberg, Ayala; Wexler, Barry; Wittenbach, Vernon; Flint, Dennis; Nudelman, Abraham

    2007-10-01

    Novel aryl chain isosters and analogues of 7-keto-8-aminopelargonic acid (KAPA) and 7,8-diaminopelargonic acid (DAPA), the vitamer intermediates involved in the biosynthetic pathway of biotin, possessing chain lengths of eight carbon atoms, were prepared and evaluated as potential herbicides. In the greenhouse test the most active compounds were the fluorinated derivative 9d and the selenophenyl/furan mixture 17m/17p, which were most active against Foxtail millet. In the more sensitive Arabidopsis test the most active substances were 9a and 17m, which displayed GR(50) (concentration of active compound causing 50% growth inhibition) values of 0.2 and 0.5 mg kg(-1) respectively (values of < 50 mg kg(-1) are considered herbicidal). PMID:17665367

  18. Inhibition of Mycobacterium tuberculosis transaminase BioA by aryl hydrazines and hydrazides.

    Science.gov (United States)

    Dai, Ran; Wilson, Daniel J; Geders, Todd W; Aldrich, Courtney C; Finzel, Barry C

    2014-03-01

    7,8-Diaminopelargonic acid synthase (BioA) of Mycobacterium tuberculosis is a recently validated target for therapeutic intervention in the treatment of tuberculosis (TB). Using biophysical fragment screening and structural characterization of compounds, we have identified a potent aryl hydrazine inhibitor of BioA that reversibly modifies the pyridoxal-5'-phosphate (PLP) cofactor, forming a stable quinonoid. Analogous hydrazides also form covalent adducts that can be observed crystallographically but are incapable of inactivating the enzyme. In the X-ray crystal structures, small molecules induce unexpected conformational remodeling in the substrate binding site. We compared these conformational changes to those induced upon binding of the substrate (7-keto-8-aminopelargonic acid), and characterized the inhibition kinetics and the X-ray crystal structures of BioA with the hydrazine compound and analogues to unveil the mechanism of this reversible covalent modification. PMID:24482078

  19. Boron compounds as anion binding agents for nonaqueous battery electrolytes

    Science.gov (United States)

    Lee, Hung Sui (East Setauket, NY); Yang, Xia-Oing (Port Jefferson Station, NY); McBreen, James (Bellport, NY); Xiang, Caili (Upton, NY)

    2000-02-08

    Novel fluorinated boron-based compounds which act as anion receptors in non-aqueous battery electrolytes are provided. When added to non-aqueous battery electrolytes, the fluorinated boron-based compounds of the invention enhance ionic conductivity and cation transference number of non-aqueous electrolytes. The fluorinated boron-based anion receptors include borane and borate compounds bearing different fluorinated alkyl and aryl groups.

  20. Establishment of a stable aryl hydrocarbon receptor-responsive HepG2 cell line.

    Science.gov (United States)

    Satsu, Hideo; Yoshida, Kazutaka; Mikubo, Ayano; Ogiwara, Haru; Inakuma, Takahiro; Shimizu, Makoto

    2014-03-26

    The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor. It heterodimerizes with aryl hydrocarbon nuclear translocator, binds to the xenobiotic-responsive element (XRE), and enhances the transcription of genes encoding xenobiotic metabolizing enzymes. AHR also plays important roles in the inhibition of intestinal carcinogenesis and the modulation of gut immunity. It is very important to screen for AHR-activating compounds because those are expected to produce the AHR-mediated physiological functions. Until now, AHR-mediated transcriptional activity represented by the transcriptional activity of CYP1A1 in luciferase assay has been applied as a screening procedure for AHR-activating compounds. However, the AHR-mediated transcriptional activity did not necessarily correspond with the CYP1A1 transcriptional activity. To evaluate AHR-mediated transcriptional activity more specifically, and to screen for AHR-activating compounds, we establish a stable AHR-responsive HepG2 cell line by co-transfection of an AHR expression vector and an AHR-responsive vector (pGL3-XRE) containing a luciferase gene and three tandemly arranged XRE elements into a human hepatoma derived cell line, HepG2. The induction of luciferase activity in the stable AHR-responsive HepG2 cell line by typical AHR activators occurred in time- and concentration-dependent manners. By assessing the AHR target genes CYP1A1, UGT1A1, and ABCG2, an AHR activator-mediated induction was observed at mRNA level. Furthermore, the AHR activator-mediated induction of luciferase activity was positively correlated with the mRNA levels of CYP1A1, UGT1A1, and ABCG2. These findings verified the usefulness of the established stable AHR-responsive HepG2 cell line for the screening of AHR-activating compounds. PMID:24667997

  1. Structural, spectroscopic, magnetic and electrochemical studies of monomer N-substituted-sulfanilamide copper (II) complex with 2,2'-bipyridine.

    Science.gov (United States)

    Öztürk, Filiz; Bulut, ?clal; Bulut, Ahmet

    2015-03-01

    A novel copper (II) complex of sulfamethazine (4-amino-N-[4,6-dimethyl-2-pyrimidinyl] benzene sulfonamide, Hsmz) ([Cu(smz)2bipy]?0.8H2O; bipy: 2,2'-bipyridine) has been synthesized and characterized by single crystal X-ray diffraction, EPR, IR, UV-vis and electrochemical methods. The single crystal X-ray analysis indicated that the compound crystallizes in the monoclinic space group P21/c with Z=4. The central copper (II) ion is coordinated by two bidentate sulfamethazine anions through the nitrogen atoms together with one bidentate 2,2'-bipyridine ligand forming the octahedral geometry. The characteristic vibration bands support the X-ray analysis results. The EPR spectral analysis has led to that the ground state wave function of the unpaired electron of copper ion is [Formula: see text] ((2)B1g state) and also indicated that the metal ions are located in distorted octahedral sites (D4h) elongated along the z-axis. The electrochemical studies of the complex were also carried out to determine the active sites of the ligands. The cyclic and square wave voltammetric techniques have been used to determine the complex. PMID:25459691

  2. Advanced hybrid fluoropolymers from the cycloaddition of aryl trifluorovinyl ethers

    Science.gov (United States)

    Ligon, S. Clark, Jr.

    This dissertation discusses the synthesis of aryl trifluorovinyl ethers and their cycloaddition polymerization to give perfluorocyclobutyl (PFCB) polymers. To explore the stereochemistry of these polymers, simple monomfunctional aryl trifluorovinyl ethers were dimerized and the resultant cis and trans isomers were separated. Differences in structure help to improve understanding of the amorphous nature of the bulk PFCB polymeric material. To apply this knowledge, crown ether containing perfluorocyclobutyl (PFCB) polymers were synthesized for use in lithium ion battery applications. While poor solubility has hindered further development of these materials, slight modifications to structure may provide a solution. Also described is a fluorinated aryl vinyl ether and its attempted copolymerization with chlorotrifluoroethylene. While this copolymerization did not yield the desired materials, novel semifluorinated phenol precursors have been utilized in reactions with carboxylic acids to give polyesters and most recently with phosgene like species to give polycarbonates. Next, PFCB polymers were post functionalized with fluoroalkyl tethers to improve oleophobicity and hydrophobicity without decreasing thermal stability or optical clarity. In addition, various silica nanostructures were functionalized with aryl trifluorovinyl ethers. This includes the reaction of aryl silanes to give trifluorovinyl ether functional POSS and their polymerization to provide PFCB hybrid materials. Silane coupling agents were also used to functionalize colloidal silica and fumed silica nanoparticles. These procedures allow excellent dispersion of the silica nanoparticles throughout the fluoropolymer matrix. Finally, the reaction of aryl trifluorovinyl ether with nonfluorinated alkenes and alkynes was explored. In these reactions, the fluorinated olefin adds with the hydrocarbon olefin to give semifluorinated cyclobutanes (SFCB) and with the alkyne to give semifluorinated cyclobutene. The reaction with alkenes has been applied to bis functional acrylates and styrenics to grow SFCB polymers similar to the PFCB polymers. Also, the fluoroolefin was shown to add to multiple alkynes to give six membered ring adducts. These hetero cycloaddition reactions, which occur at temperatures well below those required to add the aryl trifluorovinyl ethers to themselves, provide multiple pathways for the development of new hybrid fluoropolymer materials.

  3. Synthesis and biological evaluation of a novel series of aryl S,N-ketene acetals as antileishmanial agents.

    Science.gov (United States)

    Suryawanshi, S N; Kumar, Santosh; Tiwari, Avinash; Shivahare, Rahul; Chhonker, Yashpal Singh; Pandey, Susmita; Shakya, Nishi; Bhatta, Rabi Sankar; Gupta, Suman

    2013-07-01

    A series of aryl S,N-ketene acetals 7(a-f) was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against Leishmania donovani. All the 6 compounds exhibited significant in vitro activity against intracellular amastigotes of L. donovani with IC50 values ranging from 1.2 to 3.5 ?M and were found promising as compared with reference drugs, sodium stibogluconate (SSG) and paromomycin. On the basis of good selectivity indices (SI), they were further tested for their in vivo potential against L. donovani/hamster model. Two compounds 7a and 7b showed significant inhibition of parasite multiplication, 72% and 83%, respectively. These compounds were comparable with SSG and superior to paromomycin. Preliminary in vitro metabolic investigations were also performed to assess the metabolic stability and in vitro hepatic intrinsic clearance (Clint) of compound 7b in hamster liver microsomes. PMID:23673014

  4. 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.

    Czech Academy of Sciences Publication Activity Database

    Agelis, G.; Resvani, A.; Durdagi, S.; Spyridaki, K.; T?mová, Tereza; Slaninová, Ji?ina; Giannopoulos, P.; Vlahakos, D.; Liapakis, G.; Mavromoustakos, T.; Matsoukas, J.

    2012-01-01

    Ro?. 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

  5. N-sulphoconjugation of alicyclic, alkyl- and aryl-amines in vivo and in vitro.

    Science.gov (United States)

    Iwasaki, K; Shiraga, T; Noda, K; Tada, K; Noguchi, H

    1986-07-01

    Radioactive 35S in 3'-phosphoadenosine 5'-phosphosulphate was incorporated into alicyclic, alkyl- and aryl- amines in the presence of hepatic 105 000 g supernatants of female rats. 4-Phenylpiperazine, 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP), 1,2,3,4-tetrahydroisoquinoline, N-methylbenzylamine, desmethylzotepine and desmethylzimeldine showed the highest conjugation with 35SO3 among the amines tested. Incorporation of 35SO3 into alicyclic and alkyl-amines was higher at pH 10.0 than at pH 7.4 but the incorporation into arylamines was the opposite. A greater amount of 35SO3 was incorporated into the secondary alkylamines than the corresponding primary amines. Radioactive reaction products were identified as N-sulphoconjugates of amines by comparison on t.l.c. with synthetic authentic compounds. Reaction products of desmethylimipramine (DMI) and PTHP in vitro were isolated as their sulphoconjugates, identified by comparison of field desorption mass spectra, u.v. spectra, retention time on h.p.l.c. and RF values on t.l.c. with synthetic standards. DMI N-sulphonate and PTHP N-sulphonate were detected in the body of female rats treated orally with DMI and PTHP, respectively. These results indicate that N-sulphoconjugation is a common metabolic pathway of alicyclic, alkyl- and aryl-amines in vivo and in vitro. PMID:3019024

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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.

  8. Pd(0)/PR3-Catalyzed Intermolecular Arylation of sp3 C–H Bonds

    Science.gov (United States)

    Wasa, Masayuki; Engle, Keary M.; Yu, Jin-Quan

    2009-01-01

    Pd(0)-catalyzed intermolecular arylation of sp3 C–H bonds has been achieved using PR3/ArI. This protocol can be used to arylate a variety of aliphatic carboxylic acid derivatives, including a number of bioactive drug molecules. The use of fluorinated aryl iodides also allows for the introduction of fluorine into a molecule of interest. PMID:19580277

  9. Synthesis, insecticidal, and acaricidal activities of novel 2-aryl-pyrrole derivatives containing ester groups.

    Science.gov (United States)

    Zhao, Yu; Li, Yongqiang; Ou, Xiaoming; Zhang, Pengxiang; Huang, Zhiqiang; Bi, Fuchun; Huang, Runqiu; Wang, Qingmin

    2008-11-12

    A series of novel 2-aryl-pyrrole derivatives containing ester groups were synthesized, and their structures were characterized by (1)H NMR spectroscopy and elemental analysis. The insecticidal activities against oriental armyworm, mosquito, diamondback moth, green rice leafhopper, and bean aphids and acaricidal activities against spider mite of these new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal and acaricidal activities. The insecticidal activities against oriental armyworm of compounds IVa, IVd, IVe, IVf, IVg, IVi, IVk, and IVp were equal to commercialized Chlorfenapyr, and the insecticidal activities of most of compounds IVb, IVc, IVd, IVf, IVg, IVj, IVk, IVl, IVs, IVt, IVu, IVw, IVx, IVz, and Chlorfenapyr against mosquito at 0.10 mg kg (-1) were 100%, and the acaricidal activities of compounds IVd, IVe, IVf, IVg, IVh, IVi, and IVk were equal or superior to Chlorfenapyr. Especially, the results indicated that the acaricidal activity of [4-bromo-2-(4-chlorophenyl)-3-cyano-5-(trifluoromethyl)pyrrol-1-yl]methyl 3-methylbutanoate ( IVg) against spider mite was 2.65-fold as high as that of Chlorfenapyr from the value of LC 50. PMID:18937487

  10. Sequential coupling approach to the synthesis of nickel(II) complexes with N-aryl-2-amino phenolates.

    Science.gov (United States)

    Fuse, Shinichiro; Tago, Hiroaki; Maitani, Masato M; Wada, Yuji; Takahashi, Takashi

    2012-10-01

    A sequential multicomponent coupling approach is a powerful method for the construction of combinatorial libraries because structurally complex and diverse molecules can be synthesized from simple materials in short steps. In this paper, an efficient synthesis of nickel(II) complexes with N-aryl-2-amino phenols via a sequential three-step coupling approach is described, for potential use in nonlinear optical materials, bioinspired catalytic systems, and near-infrared absorbing filters. Seventeen N-aryl-2-amino phenolates were successfully synthesized in high yields based on the coupling of 3,5-di-tert-butylbenzene-1,2-diol with a pivotal aromatic scaffold, 4-bromo-2-iodo-aniline, followed by sequential Suzuki-Miyaura coupling with aryl boronates. A total of 16 analytically pure nickel(II) complexes with N-aryl-2-amino phenolates were obtained from 17 complexation trials. The procedure allowed us to assemble 4 components in high yields without protection, deprotection, oxidation or reduction steps. Various building blocks that included electron-donating, electron-withdrawing, and basic were used, and readily available, nontoxic and environmentally benign substrates and reagents were employed with no generation of toxic compounds. No strict anhydrous or degassed conditions were required. Absorption spectroscopic measurement of the synthesized nickel(II) complexes revealed that the ortho-substituent Ar(1) exerted more influence on the absorption wavelength of the complexes than the para-substituent Ar(2). On the other hand, both substituents Ar(1) and Ar(2) influenced the molar absorptivity values. These observations should be useful for the design of new and useful nickel(II) complexes as near-infrared chromophores. PMID:22916832

  11. Synthesis of thiophene oligomers via organotin compounds

    International Nuclear Information System (INIS)

    2-Trimethylstannylterthiophene coupes with functionalized aryl bromides and substituted bromothiophenes in the presence Bis (triphenylphenylphosphine) palladium (II) chloride to give substituted terthiophenes and substituted quaterthiophenes, respectively. Also, 3-trimethylstannylthiophene and 2-trimethylstannylthiophene couple with substituted 2,5-dibromothiophenes to give substituted branched terthiophenes and substituted ?-terthiophenes, respectively. The structures of the new compounds were confirmed by elemental analysis, mass spectrometry, and H-NMR spectral data. (authors). 18 refs., 2 figs

  12. Synthesis of novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones and evaluation of their biocidal effects.

    Science.gov (United States)

    Khurana, Jitender M; Magoo, Devanshi; Aggarwal, Komal; Aggarwal, Nisha; Kumar, Rajesh; Srivastava, Chitra

    2012-12-01

    Novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones have been synthesized in high yields by treatment of the corresponding oxo analogs with Lawesson's reagent. The structure has been confirmed by X-ray analysis. The compounds were tested for in vitro antifungal activity against Rhizoctonia bataticola, Sclerotium rolfsii, Fusarium oxysporum and Alternaria porii. The compounds exhibited moderate to good activity against all pathogens. Insecticidal activity of these compounds against Spodoptera litura was observed to be comparable to commercial pyrethroid insecticide, cypermethrin. The urease inhibitory activity has also been studied. PMID:23153816

  13. Induction of Mouse UDP-Glucuronosyltransferase mRNA Expression in Liver and Intestine by Activators of Aryl-Hydrocarbon Receptor, Constitutive Androstane Receptor, Pregnane X Receptor, Peroxisome Proliferator-Activated Receptor ?, and Nuclear Factor Erythroid 2-Related Factor 2

    OpenAIRE

    Buckley, David B.; Klaassen, Curtis D.

    2009-01-01

    UDP-glucuronosyltransferases (UGTs) catalyze the addition of UDP-glucuronic acid to endo- and xenobiotics, enhancing their water solubility and elimination. Many exogenous compounds, such as microsomal enzyme inducers (MEIs), alter gene expression through xenobiotic-responsive transcription factors, namely, the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor ? (PPAR?), and ...

  14. Triazolines 26: 1-Aryl-5-amido-1,2,3-triazolines, a new group of triazoline anticonvulsants. Effect of 5-substitution on anticonvulsant activity.

    Science.gov (United States)

    Kadaba, P K

    1996-01-01

    Studies in our laboratories have led to the discovery of the delta 2-1,2,3-triazolines as a unique family of anticonvulsant agents hitherto unknown. The anticonvulsant activity of 1,5-diaryl- and 1-aryl-5-pyridyltriazolines was previously reported; this paper describes the evaluation of two series of 1-aryl-5-amido-1,2,3-triazolines, A and B, where the 5-amido groups are (2-oxo-1-pyrrolidino)- (1-8) and (N-methyl-N-acetamido)- (9-15), respectively. The 1-aryl-5-(2-oxo-1-pyrrolidino)-1,2,3-triazolines of the A series, which are uniquely substituted with the pyrrolidinone lactam ring, a cyclic gamma-aminobutyric acid (GABA) structure, seem to function by enhancing inhibitory GABAergic mechanisms. Radioligand binding studies for the two most active triazolines 2 and 7, indicate that both compounds strongly inhibit the specific binding of [3H]GABA to GABAB receptor sites, with Ki = 1.7 and 0.91 microM respectively. The anticonvulsant activity among the various groups of triazolines studied so far appears to be dependent on the 5-substituent groups: 4-pyridyl- > 2-oxo-1-pyrrolidino- > N-methyl-N-acetamido- > 3-pyridyl > or = aryl approximately 2-pyridyl > 2-quinolyl. PMID:8881374

  15. Palladium-catalyzed direct arylation of pyridine N-oxide with 2-bromoacetanilides. Synthesis of benzisoxazolo[2,3-a]pyridinium tetrafluoroborates

    OpenAIRE

    Myers, Jeffery T.; Hanna, James M.

    2012-01-01

    The synthesis of a variety of novel benzisoxazolo[2,3-a]pyridinium tetrafluoroborates is described. These compounds are conveniently prepared from pyridine N-oxide via a microwave-promoted palladium-catalyzed direct arylation of pyridine N-oxide with 2-bromoacetanilides to give 2-(2-acetamidoaryl)pyridine N-oxides, followed by hydrolysis, diazotization and intramolecular displacement of nitrogen which affords the target benzisoxazolo[2,3-a]pyridinium tetrafluoroborates.

  16. COMPUTER AIDED DESIGN AND MOLECULAR DOCKING STUDY OF 1-N-SUBSTITUTED-3, 5-DIPHENYL-2-PYRAZOLINE DERIVATIVES AS COX–2 INHIBITORS

    Directory of Open Access Journals (Sweden)

    M Prasada Rao*, P Srinivasa Rao, Allam Appa Rao and Manda Rama Narasinga Rao

    2013-10-01

    Full Text Available Cyclooxygenase (COX catalyses the first committed step in the synthesis of prostanoids, a large family of arachidonic acid metabolites and major target of non-steroidal anti-inflammatory drugs (NSAIDs. COX-2 is the inducible isoform, rapidly expressed in several cell types in response to pro-inflammatory molecules. The interaction between the polypeptide and its corresponding receptor is highly selective. Therefore, it is of interest to inhibit COX2 in the context of inflammation. It is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process. The structure of COX 2 is screened using SP (Standard Precision method under molecular docking techniques (Computer aided Design with reference to novel 1-N-substituted-3, 5-diphenyl-2-pyrazoline derivatives. Based on their score and energy few ligands are selected to Induced Fit Docking (IFD studies and compared with the existing drug molecules. The result showed that the docked ligands maintain favorable interactions with the active site residues of COX-2.  All docking studies were performed using the molecular modeling software GLIDE of Schrödinger package.

  17. Phenyl boron-based compounds as anion receptors for non-aqueous battery electrolytes

    Science.gov (United States)

    Lee, Hung Sui (East Setauket, NY); Yang, Xiao-Qing (Port Jefferson Station, NY); McBreen, James (Bellport, NY); Sun, Xuehui (Middle Island, NY)

    2002-01-01

    Novel fluorinated boronate-based compounds which act as anion receptors in non-aqueous battery electrolytes are provided. When added to non-aqueous battery electrolytes, the fluorinated boronate-based compounds of the invention enhance ionic conductivity and cation transference number of non-aqueous electrolytes. The fluorinated boronate-based anion receptors include different fluorinated alkyl and aryl groups.

  18. Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Devadas, Balekudru; Selness, Shaun R.; Xing, Li; Madsen, Heather M.; Marrufo, Laura D.; Shieh, Huey; Messing, Dean M.; Yang, Jerry Z.; Morgan, Heidi M.; Anderson, Gary D.; Webb, Elizabeth G.; Zhang, Jian; Devraj, Rajesh V.; Monahan, Joseph B. (Pfizer)

    2012-02-28

    A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-{alpha} in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model.

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

    Directory of Open Access Journals (Sweden)

    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 ?–? stacking involving the diazacarbazole moieties and the phenyl rings of functionalized groups.

  20. Mechanisms of activation of the aryl hydrocarbon receptor by novel inducers of the CYP1A1 gene

    OpenAIRE

    Backlund, Maria

    2003-01-01

    The aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor that is responsible for the activation of several response genes, of which the best characterised is the CYP1A1 gene. The prototype high affinity ligand for the AhR is the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The present study was undertaken in an attempt to elucidate the mechanism of activation of the CYP1A1 gene by several compounds that recently have bee...

  1. Search for new anticonvulsant compounds. Part 1: Synthesis, physicochemical and anticonvulsant properties of new derivatives of alpha-amino-gamma-phthalimidobutyric acid.

    Science.gov (United States)

    Malawska, B; Zejc, A

    1995-11-01

    Synthesis and physicochemical properties of new derivatives of alpha-substituted gamma-phthalimidobutyric acid are described. N-substituted amides of alpha-(4-phenylpiperazine)-gamma- phthalimidobutyric acid were prepared by condensation of the acid with the corresponding derivatives of benzylamine in the presence of BOP reagent. 2-(4-Phenylpiperazine)- or 2-(4-benzylpiperidine)-4-phthalimidobutyric acid were esterified with alkyl bromide in the presence of DBU or tetrabutylammonium bromide as catalyst. The obtained compounds were evaluated for anticonvulsant activity. 2-(4-Phenylpiperazine)-4-phthalimidobutyric acid and three N-substituted amides of this acid displaced protection against MES and scMet-induced seizures. PMID:8570669

  2. 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

    Directory of Open Access Journals (Sweden)

    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.

  3. Phase transfer catalytic synthesis of 1-aryl(hetaryl)-2,2-di(2-butynyl)-4-hexynones and 1-aryl(hetaryl)-5-trialkylsil-1-pentynes

    International Nuclear Information System (INIS)

    Reaction of 1-aryl(hetaryl)-2,2-dipropargyl-4-pentynes with methyl iodide in the phase transfer system solid KOH / 18 crown-6 / CuBr / benzene affords 1-aryl(hetaryl)-2,2-di(2-butynyl)-4-hexynones in yields up to 58%. Reaction of phenylacetylene or 2-methyl-5-ethynylpyridine with 3-iodopropylalkyl-dimethylsilanes in the similar system leads to 1-aryl(hetaryl)-5-alkyldimethylsilyl-1-pentynes. (authors)

  4. Intramolecular direct C-H bond arylation from aryl chlorides: a transition-metal-free approach for facile access of phenanthridines.

    Science.gov (United States)

    Wu, Yinuo; Wong, Shun Man; Mao, Fei; Chan, Tek Long; Kwong, Fuk Yee

    2012-10-19

    A C-H arylation with aryl chloride is made viable through a transition-metal-free approach. In the presence of a simple diol associating with KOt-Bu, various phenanthridine derivatives can be conveniently accessed. In particular, only 10 mol % of simple and inexpensive ethylene glycol is required for this protocol. These results represent the first general examples of aryl chloride/C-H coupling under transition-metal-free conditions. PMID:23057703

  5. Interaction between antimalarial 2-aryl-3H-indol-3-one derivatives and human serum albumin.

    Science.gov (United States)

    Rakotoarivelo, Nambinina V; Perio, Pierre; Najahi, Ennaji; Nepveu, Françoise

    2014-11-26

    Binding of drugs to plasma proteins, such as albumin, is a major factor which determines their pharmacokinetics and pharmacological effects. Therefore, the interactions between human serum albumin (HSA) and four antimalarial compounds selected in the 2-aryl-3H-indol-3-one series have been investigated using UV-visible, fluorescence and circular dichroism (CD) spectroscopies. Compounds produced a static quenching of the intrinsic fluorescence of HSA. The thermodynamic parameters have shown that the binding reaction is endothermic for three compounds while exothermic for the 2-phenyl-3H-indol-3-one, 3. The interaction is entropically driven with predominant hydrophobic forces with binding affinities of the order of 10(4) M(-1). The highest binding constant is observed for 3 (K?=280nm = 4.53 × 10(4) M(-1)) which is also the less active compound against Plasmodium falciparum. Synchronous fluorescence gave qualitative information on the conformational changes of HSA while quantitative data were obtained with CD. Displacement experiments with site markers indicated that drugs bind to HSA at site I (subdomain IIA). In addition, the apparent binding constant and the binding site number were calculated in the presence of different ions. PMID:25360713

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

    Directory of Open Access Journals (Sweden)

    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 ?M, and nepitrin and homoplantagenin, which are flavone glucosides, showed marked AhR activation at 10–103 ?M.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Differential modulation of GABA(A) receptor function by aryl pyrazoles.

    Science.gov (United States)

    Mascia, Maria Paola; Ledda, Giovanni; Orrù, Alessandro; Marongiu, Alessandro; Loriga, Giovanni; Maciocco, Elisabetta; Biggio, Giovanni; Ruiu, Stefania

    2014-06-15

    Several aryl pyrazoles characterized by a different molecular structure (flexible vs constrained), but chemically related to rimonabant and AM251, were tested for their ability to modulate the function of recombinant ?1?2?2L GABAA receptors expressed in Xenopus laevis oocytes. The effects of 6Bio-R, 14Bio-R, NESS 0327, GP1a and GP2a (0.3-30 ?M) were evaluated using a two-electrode voltage-clamp technique. 6Bio-R and 14Bio-R potentiated GABA-evoked Cl(-) currents. NESS 0327, GP1a and GP2a did not affect the GABAA receptor function, but they acted as antagonists of 6Bio-R. Moreover, NESS 0327 inhibited the potentiation of the GABAA receptor function induced by rimonabant. The benzodiazepine site seems to participate in the action of these compounds. In fact, flumazenil antagonized the potentiation of the GABAA receptor induced by 6Bio-R, and NESS 0327 reduced the action of lorazepam and zolpidem. On the contrary, NESS 0327 did not antagonize the action of "classic" GABAergic modulators (propanol, anesthetics, barbiturates or steroids). In ?1?2 receptors 6Bio-R potentiated the GABAergic function, but flumazenil was still able to antagonize the potentiation induced by 6Bio-R. Aryl pyrazole derivatives activity at the GABAA receptor depends on their molecular structure. These compounds bind to both an ??? binding site, and to an ?/? site which do not require the ? subunit and that may provide structural leads for drugs with potential anticonvulsant effects. PMID:24704372

  9. Cobalt-catalyzed asymmetric hydroboration of aryl ketones with pinacolborane.

    Science.gov (United States)

    Guo, Jun; Chen, Jianhui; Lu, Zhan

    2015-03-17

    The highly enantioselective cobalt-catalyzed hydroboration reaction of aryl ketones with HBpin was developed using iminopyridine oxazoline ligands. Halides, amines, ethers, sulfides, esters and amides are well tolerated under the mild reaction conditions, demonstrating its synthetic advantage. Substituted diaryl ketones could also be hydroborated with high enantioselectivity. PMID:25719276

  10. Copper catalysed amidation of aryl halides through chelation assistance.

    Science.gov (United States)

    Kathiravan, Subban; Ghosh, Shishir; Hogarth, Graeme; Nicholls, Ian A

    2015-03-01

    A copper mediated C-N bond formation for the amidation of aryl halides using 8-aminoquinoline has been developed. This strategy provides efficient access to amides bearing two contiguous heterocyclic moieties and does not require the presence of additional ligands. PMID:25695680

  11. Improved synthesis of 3-aryl isoxazoles containing fused aromatic rings

    Science.gov (United States)

    Mirzaei, Yousef R.; Weaver, Matthew J.; Steiger, Scott A.; Kearns, Alison K.; Gajewski, Mariusz P.; Rider, Kevin C.; Beall, Howard D.; Natale, N.R.

    2012-01-01

    A critical comparison of methods to prepare sterically hindered 3-aryl isoxazoles containing fused aromatic rings using the nitrile oxide cycloaddition (NOC) reveal that modification of the method of Bode, Hachisu, Matsuura, and Suzuki (BHMS), utilizing either triethylamine as base or sodium enolates of the diketone, ketoester, and ketoamide dipolarophiles, respectively, was the method of choice for this transformation. PMID:23526841

  12. Photochemical Aryl Radical Cyclizations to Give (E-3-Ylideneoxindoles

    Directory of Open Access Journals (Sweden)

    Michael Gurry

    2014-09-01

    Full Text Available (E-3-Ylideneoxindoles are prepared in methanol in reasonable to good yields, as adducts of photochemical 5-exo-trig of aryl radicals, in contrast to previously reported analogous radical cyclizations initiated by tris(trimethylsilylsilane and azo-initiators that gave reduced oxindole adducts.

  13. Synthesis and Vasorelaxant Effect of 9-aryl-1,8-acridinediones asPotassium Channel Openers in Isolated Rat Aorta.

    Science.gov (United States)

    Imenshahidi, Mohsen; Hadizadeh, Farzin; Firoozeh-Moghadam, Asieh; Seifi, Mahmoud; Shirinbak, Atefeh; Gharedaghi, Mohammad Bagher

    2012-01-01

    ATP-sensitive potassium (KATP) channel openers have a relaxation effect due to the lower cellular membrane potential and inhibit calcium influx. There has been considerable interest in exploring KATP channel openers in the treatment of various diseases such as cardiovascular, cerebrovascular, and urinary system disease and premature labor. The purpose of this study was to synthesize 3,3,6,6-tetramethy l-9-aryl-octahydro-1,8-acridindiones and investigate their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rings of rat aortic smooth muscle. In this study, four new derivatives of 3,3,6,6-tetramethy l-9-aryl-octahydro-1,8-acridindione [2a-d] were synthesized by the reaction of 5, 5-dimethyl-1,3-cyclohexanedione with an aromatic aldehyde, 2-alkylthio-1-(4-fluorobenzyl)-5-formylimidazole or 3-substituted benzaldehyde, in the presence of ammonia in methanol. Their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rat aorta were investigated. Minoxidil was used as a standard potassium channel opener and Glibenclamide was used as a standard potassium channel blocker. The effects of compounds on KCl-induced contractile response which is an indicator of ca-channel blocking activity was also investigated and compared to that of nifedipine as a standard calcium channel blocker. Compounds 3a-d and Minoxidil relaxed the contractions exerted by using phenylephrine with the potency order as follows: Minoxidil > 3c > 3d > 3a > 3b. This effect was sensitive to the potassium channel blocker Glibenclamide. It can be concluded that these compounds act via ATP-sensitive potassium (KATP) channels. Selectivity index (SI) for these compounds and Minoxidil also shows that these compounds are selective to ATP-sensitive potassium (KATP) channels and the selectivity of compounds 3a-d is less than Minoxidil. PMID:24250444

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

    Science.gov (United States)

    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.

  15. New efficient route to dissymmetric 2,4-di(het)aryl-pyrido[3,2-d]pyrimidines via regioselective cross-coupling reactions.

    Science.gov (United States)

    Tikad, Abdellatif; Routier, Sylvain; Akssira, Mohamed; Leger, Jean-Michel; Jarry, Christian; Guillaumet, Gérald

    2007-11-01

    The first access to dissymmetric 2,4-di(het)aryl-pyrido[3,2-d]pyrimidines III is reported. Two mild alternative routes led to the rarely targeted compounds from 2,4-dichloro- and 2-chloro-4-isopropylsulfanyl-pyrido[3,2-d]pyrimidine by two successive palladium-catalyzed reactions involving an original regioselective chlorine discrimination. Alternatively, type III compounds were elaborated from 2 by C-2 chlorine further displacement of the C-4 isopropylsulfanyl group, which acted as a temporary C-4 protecting group. These results open the way to innovative synthesis strategies of various bis-functionalized pyrimidine series. PMID:17949094

  16. Inhibition of P-glycoprotein-mediated Multidrug Resistance (MDR) by N,N-bis(cyclohexanol)amine aryl esters: further restriction of molecular flexibility maintains high potency and efficacy.

    Science.gov (United States)

    Martelli, Cecilia; Dei, Silvia; Lambert, Catherine; Manetti, Dina; Orlandi, Francesca; Romanelli, Maria Novella; Scapecchi, Serena; Salerno, Milena; Teodori, Elisabetta

    2011-01-01

    Conformational modulation of the aryl portion of a set of N,N-bis(cyclohexanol)amine aryl esters (1a-d) that are potent Pgp-dependent MDR inhibitors has been performed. Toward this end the trans-3-(3,4,5-trimethoxyphenyl)acrylic acid present in set 1 was substituted with 3-(3,4,5-trimethoxyphenyl)propanoic and 3-(3,4,5-trimethoxyphenyl)propiolic moieties to give sets 2 and 3, respectively. While the introduction of 3-(3,4,5-trimethoxyphenyl)propanoic moiety resulted in a definite drop in potency and efficacy, esterification with 3-(3,4,5-trimethoxyphenyl)propiolic acid gave four isomers (3a-d) that maintain high potency and possess optimal efficacy. These results are discussed in terms of conformational flexibility of the different sets of compounds. PMID:21145739

  17. High-resolution laser spectroscopy and magnetic effect of the B?(2)E(')?X?(2)A2 (') transition of the (15)N substituted nitrate radical.

    Science.gov (United States)

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

    2015-03-21

    Rotationally resolved high-resolution fluorescence excitation spectra of the 0-0 band of the B?(2)E(')?X?(2)A2 (') transition of the (15)N 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)A2 (') (?? = 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)A2 (') (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. PMID:25796244

  18. Salen-Cu(II Complex Catalyzed N-Arylation of Imidazoles under Mild Conditions

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2013-08-01

    Full Text Available Three inexpensive and air-/moisture-stable Salen-Cu complexes 1-3 were evaluated to be a novel class of catalysts for the N-arylation of imidazoles with aryl halides. A variety of aryl iodides, bromides underwent the coupling with imida-zoles, promoted by the complex 3, in moderate to excellent yields without the protection by an inert gas.

  19. Synthesis of tricyclic heterocycles via a tandem aryl alkylation/heck coupling sequence.

    Science.gov (United States)

    Alberico, Dino; Rudolph, Alena; Lautens, Mark

    2007-02-01

    A norbornene-mediated palladium-catalyzed sequence is described in which two alkyl-aryl bonds and one alkenyl-aryl bond are formed in one pot with use of microwave irradiation. A variety of symmetrical and unsymmetrical oxygen-, nitrogen-, silicon-, and sulfur-containing tricyclic heterocycles were synthesized from a Heck acceptor and an aryl iodide containing two tethered alkyl halides. This approach was further applied to the synthesis of a tricyclic mescaline analogue. PMID:17253794

  20. 4-Aryl-4H-Naphthopyrans Derivatives: One-pot Synthesis, Evaluation of Src Kinase Inhibitory and Anti-proliferative Activities

    Directory of Open Access Journals (Sweden)

    Ali Rafinejad

    2012-01-01

    Full Text Available The one-pot, three-component reaction of ? or ?-naphthol, malonitrile and an aromatic aldehyde in the presence of Diammonium hydrogen phosphate was afforded the corresponding 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives, All target compounds were evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20 cell lines.Results Among all tested compounds, unsubstituted 4-phenyl analog 4a showed Src kinas inhibitory effect with IC50 value of 28.1 ?M and was the most potent compound in this series. Ingeneral, the compounds were moderately active against BT-20. 3-Nitro-phenyl 4e and 3- pyridinyl 4h derivatives inhibited the cell proliferation of BT-20 cells by 33% and 31.5%,respectively, and found to be more potent compared to doxorubicin (25% inhibition of cell growth. ConclusionThe data indicate that 4-aryl-4H-naphthopyrans scaffold has the potential to be optimized further for designing more potent Src kinase inhibitors and/or anticancer lead compounds.

  1. Design, synthesis, and SAR studies of 4-substituted methoxylbenzoyl-aryl-thiazoles analogues as potent and orally bioavailable anticancer agents.

    Science.gov (United States)

    Lu, Yan; Li, Chien-Ming; Wang, Zhao; Chen, Jianjun; Mohler, Michael L; Li, Wei; Dalton, James T; Miller, Duane D

    2011-07-14

    In a continued effort to improve upon the previously published 4-substituted methoxybenzoyl-aryl-thiazole (SMART) template, we explored chemodiverse "B" rings and "B" to "C" ring linkage. Further, to overcome the poor aqueous solubility of this series of agents, we introduced polar and ionizable hydrophilic groups to obtain water-soluble compounds. For instance, based on in vivo pharmacokinetic (PK) studies, an orally bioavailable phenyl-amino-thiazole (PAT) template was designed and synthesized in which an amino linkage was inserted between "A" and "B" rings of compound 1. The PAT template maintained nanomolar (nM) range potency against cancer cell lines via inhibiting tubulin polymerization and was not susceptible to P-glycoprotein mediated multidrug resistance in vitro, and markedly improved solubility and bioavailability compared with the SMART template (45a-c (PAT) vs 1 (SMART)). PMID:21557538

  2. Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists: A potential treatment for neuropathic pain.

    Science.gov (United States)

    Cho, Gyeong Hi; Kim, TaeHun; Son, Woo Seung; Seo, Seon Hee; Min, Sun-Joon; Cho, Yong Seo; Keum, Gyochang; Jeong, Kyu-Sung; Koh, Hun Yeong; Lee, Jiyoun; Pae, Ae Nim

    2015-03-15

    Glutamate is the major excitatory neurotransmitter and known to activate the metabotropic and ionotropic glutamate receptors in the brain. Among these glutamate receptors, metabotropic glutamate receptor 1 (mGluR1) has been implicated in various brain disorders including anxiety, schizophrenia and chronic pain. Several studies demonstrated that the blockade of mGluR1 signaling reduced pain responses in animal models, suggesting that mGluR1 is a promising target for the treatment of neuropathic pain. In this study, we have developed mGluR1 antagonists with an aryl isoxazole scaffold, and identify several compounds that are orally active in vivo. We believe that these compounds can serve as a useful tool for the investigation of the role of mGluR1 and a promising lead for the potential treatment of neuropathic pain. PMID:25677662

  3. Ion and molecular recognition using aryl-ethynyl scaffolding.

    Science.gov (United States)

    Vonnegut, Chris L; Tresca, Blakely W; Johnson, Darren W; Haley, Michael M

    2015-03-01

    The aryl-ethynyl linkage has been extensively employed in the construction of hosts for a variety of guests. Uses range from ion detection (e.g., of metal cations in the environment or industrial waste and of anions prevalent in nature), to molecular mimics for biological systems, and to applications targeting future safety issues (such as CO2 capture and indicators for the manufacture of chemical weapons). This Focus Review examines the utilization of the aryl-ethynyl linkage in engineering host molecules for a variety of different guests, and how the alkyne unit plays an integral part as both a rigid scaffolding section in host geometry design as well as a linker to allow conjugative communication between discrete ?-electron systems. PMID:25586943

  4. Hybrid biobattery based on arylated carbon nanotubes and laccase.

    Science.gov (United States)

    Stolarczyk, Krzysztof; Sepelowska, Ma?gorzata; Lyp, Dominika; Zelechowska, Kamila; Biernat, Jan F; Rogalski, Jerzy; Farmer, Kevin D; Roberts, Ken N; Bilewicz, Renata

    2012-10-01

    Single-walled carbon nanotubes (SWCNT) were covalently modified with anthracene and anthraquinone and used for the construction of cathodes for biocatalytic reduction of dioxygen. The nanotubes with aromatic groups casted onto the electrode increased the working surface of the electrode and enabled efficient direct electron transfer (DET) between the enzyme and the electrode. The aryl groups enter the hydrophobic pocket of the T1 center of laccase responsible for exchanging electrons with the substrate. Glassy carbon electrode covered with arylated SWCNT and coated with a layer of neutralized Nafion containing laccase was found to be a very efficient cathode in the hybrid battery. Zn wire covered with a Nafion film served as the anode. The cell parameters were determined: power density was 2 mW/cm(2) and the open circuit potential was 1.5 V. PMID:22078125

  5. Synthesis of novel aryl(heteroaryl)sulfonyl ureas of possible biological interest.

    Science.gov (United States)

    Saczewski, Franciszek; Kuchnio, Anna; Samsel, Monika; ?obocka, Marta; Kiedrowska, Agnieszka; Lisewska, Karolina; Saczewski, Jaros?aw; Gdaniec, Maria; Bednarski, Patrick J

    2010-03-01

    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 approximately 10 gave 4-dimethylamino-pyridinium arylsulfonyl-carbamoylides, while the more acidic heteroaryl sulfonamides (pKa approximately 8) furnished 4-dimethylaminopyridinium heteroarylsulfonyl carbamates. Both the carbamoylides and carbamate salts reacted with aliphatic and aromatic amines with the formation of appropriate aryl(heteroaryl)sulfonyl ureas, and therefore, can be regarded as safe and stable substitutes of the hazardous and difficult to handle aryl(heteroaryl)sulfonyl isocyanates. PMID:20335967

  6. Synthesis and protection of aryl sulfates using the 2,2,2-trichloroethyl moiety.

    Science.gov (United States)

    Liu, Yong; Lien, I-Feh Felicia; Ruttgaizer, Scott; Dove, Peter; Taylor, Scott D

    2004-01-22

    [reaction: see text] The 2,2,2-trichloroethyl (TCE) group was utilized as the first protecting group for aryl sulfates. Aryl sulfates, protected with the TCE group, were prepared in high yield by reacting phenols with chlorosulfuric acid TCE ester. Deprotection was accomplished using Pd/C-ammonium formate or with Zn-ammonium formate to give aryl sulfate monoesters in high yield. This approach to aryl sulfate synthesis was successfully applied to the construction of estrone sulfate derivatives, which could not be prepared by previous methodologies. PMID:14723530

  7. P,N,N-pincer nickel-catalyzed cross-coupling of aryl fluorides and chlorides.

    Science.gov (United States)

    Wu, Dan; Wang, Zhong-Xia

    2014-09-01

    P,N,N-Pincer nickel complexes [Ni(Cl){N(2-R2PC6H4)(2'-Me2NC6H4)}] (R = Ph, 3a; R = Pr(i), 3b; R = Cy, 3c) were synthesized and their catalysis toward the Kumada or Negishi cross-coupling reaction of aryl fluorides and chlorides was evaluated. Complex 3a effectively catalyzes the cross-coupling of (hetero)aryl fluorides with aryl Grignard reagents at room temperature. Complex 3a also catalyzes the cross-coupling of (hetero)aryl chlorides and arylzinc reagents at 80 °C with low catalyst loadings and good functional group compatibility. PMID:25012049

  8. Aryl hydrocarbon receptor activity modulates prolactin expression in the pituitary

    OpenAIRE

    Moran, Tyler B.; Brannick, Katherine E.; Raetzman, Lori T.

    2012-01-01

    Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotroph and lactotroph adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, pote...

  9. Copper Mediated Difluoromethylation of Aryl and Vinyl Iodides

    OpenAIRE

    Fier, Patrick S.; Hartwig, John F.

    2012-01-01

    Selectively fluorinated molecules are important as materials, pharmaceuticals, and agrochemicals, but their synthesis by simple, mild, laboratory methods is challenging. We report a straightforward method for the cross-coupling of a difluoromethyl group with readily available reagents to form difluoromethylarenes. The reaction of electron-neutral, electron-rich, and sterically hindered aryl and vinyl iodides with the combination of CuI, CsF and TMSCF2H leads to the formation of difluoromethyl...

  10. Photoredox Activation for the Direct ?-Arylation of Ketones and Aldehydes

    OpenAIRE

    Pirnot, Michael T.; Rankic, Danica A.; Martin, David B. C.; Macmillan, David W. C.

    2013-01-01

    The direct ?-activation of saturated aldehydes and ketones has long been an elusive transformation. We found that photoredox catalysis in combination with organocatalysis can lead to the transient generation of 5?-electron ?-enaminyl radicals from ketones and aldehydes that rapidly couple with cyano-substituted aryl rings at the carbonyl ?-position. This mode of activation is suitable for a broad range of carbonyl ?-functionalization reactions and is amenable to enantioselective catalysis.

  11. Palladium- (and nickel-) catalyzed vinylation of aryl halides†

    OpenAIRE

    Denmark, Scott E.; Butler, Christopher R.

    2008-01-01

    Functionalized styrenes are extremely useful building blocks for organic synthesis and for functional polymers. One of the most general syntheses of styrenes involves the combination of an aryl halide with a vinyl organometallic reagent under catalysis by palladium or nickel complexes. This Feature Article provides the first comprehensive summary of the vinylation methods currently available along with a critical comparison of the efficiency, cost and scope of the methods.

  12. TBAHS CATALYZED COUPLING REACTIONS OF ARYL IODIDES AND ARYL BROMIDES WITH THIOLS UNDER SOLVENT FREE CONDITIONS TBAHS katalysierten Kupplungen von Aryliodiden und-Arylbromiden mit Thiolen unter lösungsmittelfreien freien Bedingungen

    Directory of Open Access Journals (Sweden)

    Gajendera Singha, Ajay kumarb , Sakshi Malikc, Preeti Chaudharyd

    2013-04-01

    Full Text Available A recyclable and efficient Tetrabutylammonium hydrogensulfate (TBAHS catalysed coupling reaction of aryl halides (iodide and bromide with aryl and alkyl thiols under solvent-free conditions were developed.

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

    OpenAIRE

    Ali, Ruhi; Siddiqui, Nadeem

    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 analys...

  14. High-Intensity Ultrasound and Microwave, Alone or Combined, Promote Pd/C-Catalyzed Aryl-Aryl Couplings

    OpenAIRE

    Cravotto, Giancarlo

    2005-01-01

    Pd-catalyzed homo- and cross-couplings of boronic acids and aryl halides were successfully carried out both in aqueous media under high-intensity ultrasound (US) and in DME under microwave (MW). Heterogeneous catalysis with Pd/C was employed, avoiding phosphine ligands and phase-transfer catalysts. In a trial series involving 15 different iodo- and bromoaryls and 7 boronic acids, both energy sources drastically reduced reaction times affording biaryls in acceptable to good yields. ...

  15. Synthesis and antimicrobial activity of N-substituted-?-amino acid derivatives containing 2-hydroxyphenyl, benzo[b]phenoxazine and quinoxaline moieties.

    Science.gov (United States)

    Mickevi?ien?, Kristina; Baranauskait?, R?ta; Kantminien?, Kristina; Stasevych, Maryna; Komarovska-Porokhnyavets, Olena; Novikov, Volodymyr

    2015-01-01

    3-[(2-Hydroxyphenyl)amino]butanoic and 3-[(2-hydroxy-5-methyl(chloro)phenyl)amino]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. PMID:25689642

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Microwave assisted condensation reactions of 2-aryl hydrazonopropanals with nucleophilic reagents and dimethyl acetylenedicarboxylate.

    Science.gov (United States)

    Al-Zaydi, Khadijah M; Borik, Rita M

    2007-01-01

    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. PMID:17960106

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Thioxophosphoranyl aryl- and heteroaryloxiranes as the representants of a new class of metallocarboxypeptidase inhibitors.

    Science.gov (United States)

    Fernández, Daniel; Illa, Ona; Avilés, Francesc X; Branchadell, Vicenç; Vendrell, Josep; Ortuño, Rosa M

    2008-05-01

    A novel and potent family of metallocarboxypeptidase inhibitors based on thioxophosphoranyl oxiranes is presented. These compounds bear aryl or heteroaryl substituents with trans-stereochemistry with respect to the phosphorylated group and they have been synthesized by the addition of [bis(diisopropylamino)phosphino](trimethylsilyl)carbene to the corresponding aldehydes and the subsequent thiolation of the phosphine. These oxiranes contain a tetrahedral P atom harboring shielded N,N-groups. The screening of their biological activity as metallocarboxypeptidase inhibitors and some structural studies, as well as full experimental details for the new compounds, is disclosed. Thus, from the analysis of their activity against the prototypical metallocarboxypeptidases A and B (CPA and CPB), we have observed that hydrophobic phosphorylated oxiranes perform better as CPB inhibitors, reaching K(i) values comparable to classical synthetic carboxypeptidase inhibitors. X-ray diffraction analysis revealed that the packing in the structure of one phosphorylated oxirane is mediated mainly by hydrophobic contacts and that the N,N-groups are highly flexible. Consequently, phosphorylated oxiranes might constitute an attractive material for subsequent improvements in the design of novel inhibitors against human proteolytic enzymes with enhanced oral availability. PMID:18396051

  20. Synthesis and antileishmanial activity of new 1-aryl-1H-pyrazole-4-carboximidamides derivatives

    Scientific Electronic Library Online (English)

    Maurício S. dos, Santos; Adriana O, Gomes; Alice M. R, Bernardino; Marcos C. de, Souza; Misbahul A, Khan; Monique A. de, Brito; Helena C, Castro; Paula A, Abreu; Carlos R, Rodrigues; Rosa M. M. de, Léo; Leonor L, Leon; Marilene M, Canto-Cavalheiro.

    2011-02-01

    Full Text Available SciELO Brazil | Language: English Abstract in portuguese A quimioterapia para as leishmanioses, doenças causadas por protozoários do gênero Leishmania, ainda permanece ineficiente em diversos tratamentos. Portanto, existe a necessidade de pesquisa por novos fármacos. Nesse trabalho, foram sintetizados derivados 1-aril-1H-pirazol-4-carboximidamidas, avalia [...] das as atividades leishmanicida e os efeitos citotóxicos in vitro, e realizado um estudo de relação estrutura-atividade (REA) com a série de compostos. O composto 2 apresentou um perfil de atividade que pode ser melhorado através de estratégias de modificação molecular da química medicinal. Abstract in english 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Implications of cytochrome 450 isoenzymes, aryl-esterase and oxonase activity in the inhibition of the acetylcholinesterase of Chirostoma jordani treated with phosphorothionate pesticides.

    Science.gov (United States)

    Dzul-Caamal, Ricardo; Domínguez-López, M Lilia; García-Latorre, Ethel; Vega-López, Armando

    2012-10-01

    Organophosphate pesticides must be metabolized by cytochrome-P450 isoenzymes such CYP 2C19 as CYP 3A4 to induce neurotoxicity, but damage apparently depends on the activity of aryl esterases of the oxonase type that are involved in detoxication of these compounds. However, information on this subject is not available in fish. Chirostoma jordani has sustained significant population reductions, probably due to changes in land-use as well as pesticide impact; nevertheless, no specific studies demonstrating this are available. This study shows for the first time that the activity of cytochrome-P450 isoenzymes (CYP 2B6, CYP 2C19, CYP 3A4) in C. jordani is involved in diazinon and chlorpyrifos bioactivation. However, higher toxicity of chlorpyrifos cannot be explained solely because its bioactivation. Differences in toxicity between both pesticides are due to the activity of aryl esterases and oxonases that are responsible for oxon detoxication. Both hepatic enzymes metabolize diazoxon more efficiently than chlorpyrifos oxon. At lethal concentrations, detoxication is particularly important since mortality was lower with diazinon (LC50=1.5 ?g/L) than with chlorpyrifos (LC50=0.17 ?g/L). At sublethal levels, maximum acetylcholinesterase inhibition took place at 4h in both brain and muscle and was of lower magnitude in diazinon-treated fish. This is due to the higher affinity of both aryl esterases for diazoxon, which allows higher detoxication rates and therefore greater recovery of acetylcholinesterase activity. PMID:22835727

  3. Molecular and crystal structures of some novel derivatives of 3-aryl-7-arylidene-3,3a,4,5,6,7-hexahydroindazoles

    International Nuclear Information System (INIS)

    The stereochemical aspects of the interaction of 2,6-bis(arylidene)-cyclohexanone and 2,6-bis(arylidene)-3-methylcyclohexanone with arylhydrazine (aryl is phenyl or 4-nitrophenyl) and methylhydrazine are investigated using X-ray diffraction analysis. The molecular structure of the 3-aryl-7-arylidene-3,3a,4,5,6,7-hexahydroindazoles synthesized is determined by X-ray diffraction analysis for the first time. It is established that the stereochemistry of the products of the interaction between the cyclohexanone derivatives and arylhydrazines depends on the electronic nature of the substituent in the aryl group. Two regioisomeric products with different positions of the methyl group in the cyclohexane ring with respect to the arylidene fragment are synthesized by the reaction of 2,6-bis(4-methoxybenzylidene)-3-methylcyclohexanone with methylhydrazine. The influence of the substituents at the nitrogen atom of the pyrazoline ring on the intramolecular electronic interactions and the geometry of the heterocycle in the compounds under investigation is discussed

  4. Synthesis, Characterization of Cellulose Grafted N-Oxide Reagent and Its Application in Oxidation of Alkyl/Aryl Halides

    Directory of Open Access Journals (Sweden)

    Poonam K. Dhiman

    2011-03-01

    Full Text Available Oxidation of aliphatic and aromatic halides by N-oxide functionalities supported on 4- vinyl pyridine, (4-VP, grafted cellulose is reported in the present manuscript. Synthesis of graft copolymer of cellulose and poly 4-vinyl pyridine, poly(4-VP, has been carried out using ceric ions as redox initiator. Post-grafting treatment of CellO-g-poly (4-VP with 30% H2O2 in acetic acid gives Cellulose-g-poly (4-VP N-oxide, the polymeric supported oxidizing reagent. The polymeric support, CellO-g-poly (4-VP N-oxide, has been used for oxidation reactions of different alkyl / aryl halide such as 1-bromo-3-methyl butane, 2-bromo propane,1-bromo heptane and benzyl chloride. The polymeric reagent was characterized by IR and thermo-gravimetric analysis. The oxidized products were characterized by FTIR and H1NMR spectral methods. The reagent was reused for the oxidation of a fresh alkyl / aryl halides and it was observed that the polymeric reagent oxidizes the compounds successfully but with little lower product yield.

  5. Stereoselective copper-catalyzed Chan-Lam-Evans N-arylation of glucosamines with arylboronic acids at room temperature.

    Science.gov (United States)

    Bruneau, Alexandre; Brion, Jean-Daniel; Alami, Mouad; Messaoudi, Samir

    2013-09-28

    An efficient and practical N-arylation of glycosylamines with substituted aryl boronic acids has been established. Using Cu(OAc)2 and pyridine at room temperature under air atmosphere, the protocol proved to be general, and a variety of aryl N-glycosides have been prepared in good to excellent yields with exclusive ? selectivity. PMID:23928939

  6. Ligand-free copper-catalyzed C?S coupling of aryl iodides and thiols

    OpenAIRE

    Sperotto, E.; Klink, G. P. M.; Vries, Johannes G.; Koten, G.

    2008-01-01

    A protocol for the copper-catalyzed aryl?sulfur bond formation between aryl iodides and thiophenols is reported. The reaction is catalyzed by a low amount (1?2.5 mol %) of readily available and ligand-free copper iodide salt. A variety of diaryl thioethers are synthesized under relatively mild reaction conditions with good chemoselectivity and functional group tolerance.

  7. Efficient synthesis of 5-substituted 2-aryl-6-cyanoindolizines via nucleophilic substitution reactions

    Directory of Open Access Journals (Sweden)

    Vasilevich Natalya I

    2005-10-01

    Full Text Available Abstract 2-Aryl-6-cyano-7-methyl-5-indolizinones were successfully converted into 2-aryl-5-chloro-6-cyano-7-methylindolizines. The obtained 5-chloroindolizines readily underwent nucleophilic substitution at position 5 leading in high yields to novel 5-functionalised indolizines.

  8. Visible light-mediated arylalkylation of allylic alcohols through concomitant 1,2-aryl migration.

    Science.gov (United States)

    Huang, Hong-Li; Yan, Hang; Yang, Chao; Xia, Wujiong

    2015-03-01

    A photocatalytic process for selective arylalkylation of allylic alcohols with ?-bromo diethyl malonate has been developed. The reaction provided a straightforward approach to synthesize ?-aryl-?-alkylated ketones via unique 1,2-aryl migration. The procedure is highlighted by its operational simplicity and mild reaction conditions. PMID:25703263

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

    Science.gov (United States)

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

    2015-04-22

    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 ?- and ?-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

  10. Cu-Catalyzed Arylation of Phenols: Synthesis of Sterically Hindered and Heteroaryl Diaryl Ethers

    OpenAIRE

    Maiti, Debabrata; Buchwald, Stephen L.

    2009-01-01

    Cu-catalyzed O-arylation of phenols with aryl iodides and bromides can be performed under mild condition in DMSO/K3PO4 with use of picolinic acid as the ligand for copper. This method tolerates a variety of functional groups and is effective in the synthesis of hindered diaryl ethers and heteroaryl ethers.

  11. Rational ligand design for the arylation of hindered primary amines guided by reaction progress kinetic analysis.

    Science.gov (United States)

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

    2015-03-01

    We report the Pd-catalyzed arylation of very hindered ?,?,?-trisubstituted primary amines. Kinetics-based mechanistic analysis and rational design have led to the development of two biarylphosphine 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. PMID:25651374

  12. Evaluation of sensitizers found in wastewater from paper recycling areas, and their activation of the aryl hydrocarbon receptor in vitro.

    Science.gov (United States)

    Terasaki, Masanori; Yasuda, Michiko; Shimoi, Kayoko; Jozuka, Kazuhiko; Makino, Masakazu; Shiraishi, Fujio; Nakajima, Daisuke

    2014-09-15

    The in vitro potential of sensitizers and related compounds (SRCs) originating from impurities in waste paper in activating the human aryl hydrocarbon receptor (AhR) ? was assessed using yeast reporter gene as well as cytochrome P450 (CYP)1A1 and ethoxyresorufin O-deethylase (EROD) assays. In the yeast assay, eight compounds exhibited agonist activity, and their activity relative to ?-naphthoflavone (BNF) ranged from 1.4 × 10(-4) to 8.3 × 10(-2), with the highest activity observed for benzyl 2-naphthyl ether (BNE). In the EROD assay, six compounds caused a more significant induction of CYP1A-dependent activity than did the vehicle control at 50 ?M (pwaste paper recycling area was fractioned using solid-phase extraction (SPE) combined with a C18 disk and florisil cartridge. In gas chromatography-mass spectrometry (GC-MS) analysis, SRCs were detected in the first fraction, at a total concentration of 5.5 ?g/L. This fraction also activated AhR, and its activity, expressed as a BNF equivalent value, was 0.42 nM in the yeast assay. The contribution ratio of active compounds accounted for up to 34% and 4.4% observed activity of the fraction and total samples, respectively. To our knowledge, this is the first study to show that paper industry-related compounds, namely aromatic sensitizers, activate AhR by using a yeast assay and HepG2 cells. PMID:24950494

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

    Directory of Open Access Journals (Sweden)

    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.

  14. New Pd(II) complexes of the synthesized 1-N-substituted thiosemicarbazones of 3-indole carboxaldehyde: characterization and antiamoebic assessment against E. histolytica.

    Science.gov (United States)

    Husain, Kakul; Bhat, Abdul Roouf; Azam, Amir

    2008-09-01

    Reaction of 3-indole carboxaldehyde with aminothiocarbonyl hydrazines resulted in the formation of 3-indole carboxaldehyde thiosemicarbazones (TSCs) 1-13. The synthesized thiosemicarbazones were used as ligands in the formation of [Pd(TSC)Cl2] complexes with palladium(II) metal ion precursor, [Pd(DMSO)2Cl2]. The chemical structures of all the compounds were established by electronic, IR, 1H NMR and 13C NMR spectral data. The structure of the complexes was further established by FABMS and DTA. It is concluded that the thione sulphur and the azomethine nitrogen atom of the ligands are bonded to the metal ion. The testing of the antiamoebic activity of these compounds against the protozoan parasite Entamoeba histolytica suggests that compounds 5, 3a, 5a and 8a-13a might be endowed with important antiamoebic properties since they showed less IC50 values than metronidazole. Moreover, compound 12a displays remarkable antiamoebic activity than metronidazole (IC50 values of 0.29 vs 1.81 microM, respectively). MTT assay showed that the compounds are non-toxic to human kidney epithelial cell line. PMID:18222017

  15. A New Method for Production of Chiral 2-Aryl-2-fluoropropanoic Acids Using an Effective Kinetic Resolution of Racemic 2-Aryl-2-fluoropropanoic Acids

    Directory of Open Access Journals (Sweden)

    Atsushi Tengeiji

    2012-06-01

    Full Text Available We report a new method for the preparation of chiral 2-aryl-2-fluoropropanoic acids, including 2-fluoroibuprofen, a fluorinated analogue of non-steroidal anti-inflammatory drugs (NSAIDs, by the kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids using enantioselective esterification. By applying pivalic anhydride (Piv2O as a coupling agent, bis(?-naphthylmethanol [(?-Np2CHOH] as an achiral alcohol, and (+-benzotetramisole (BTM as a chiral acyl-transfer catalyst, a series of racemic 2-aryl-2-fluoropropanoic acids were kinetically separated to afford the optically active carboxylic acids and the corresponding esters with good to high enantiomeric excesses. This technology can provide a convenient approach to furnish the chiral ?-fluorinated drugs containing quaternary carbons at the ?-positions in the 2-aryl-2-fluoropropanoic acid structure.

  16. Regioselectivity of Arylation of 2,3’-Biquinolyl Dianion

    Directory of Open Access Journals (Sweden)

    Yu. I. Smushkevich

    1999-04-01

    Full Text Available The dianion of 2,3’-biquinolyl with aryl- and hetaryl halides forms the products of arylation to 4’-position, which on treatment with alkyl halides or water yield 1’-alkyl-1’,4’dihydro-2,3’-biquinolyls or 4’-aryl-1’,4’-dihydro-2,3’-biquinolyls respectively. The oxidation of the latter leads to 4’-aryl-2,3’-biquinolyls. The cation dependence of the arylation is shown.

  17. Structure-activity relationship study of a series of N-substituted piperazinyl-fluoroquinolones as anti-Helicobacter pylori agents.

    Science.gov (United States)

    Foroumadi, A; Safavi, M; Emami, S; Siavoshi, F; Najjari, S; Safari, F; Shafiee, A

    2008-09-01

    Helicobacter pylori is now recognized as the primary etiological factor associated with gastritis, peptic ulcer disease and gastric cancers. Fluoroquinolones have been shown to be active against H. pylori. For develop new anti-H. pylori agents, we have investigated the SAR of a series of N-(phenethyl)piperazinyl quinolones for their antimicrobial activity against H. pylori. The anti-H. pylori activity of synthesized compounds along with commercially available anti-H. pylori agents such as metronidazole, and parent quinolones was evaluated by the disc diffusion bioassay. The results indicated that the potency and anti-H. pylori activity profile of the quinolones is highly dependent on the type of substituent at N-1 and the structure of phenethyl unit on piperazine ring. Most compounds containing a cyclopropyl at N-1 exhibited good activity against H. pylori strains. Among them, ciprofloxacin derivative 13 containing 2-methoxyimino-2-(2-chlorophenyl)ethyl moiety was the most active compound. PMID:18782047

  18. Synthesis of N-Substituted Derivatives of N-(4-(N- (5-Chloro-2 methoxyphenyl)sulfamoyl)phenyl)acetamide with potential antiurease activity

    International Nuclear Information System (INIS)

    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. Synthesis, Characterization and Antibacterial Activity of New 1,2- and 1,4-Bis(N' -Substituted Thioureido)benzene Derivatives

    Scientific Electronic Library Online (English)

    Aamer, Saeed; Naeem, Abbas; Zaman, Ashraf; Michael, Bolte.

    2013-08-01

    Full Text Available SciELO South Africa | Language: English Abstract in english Synthesis of two series of 1,2- and 1,4-bis(thioureido)benzene derivatives was accomplished by the treatment of corresponding alkanoyl/aroyl chlorides with potassium thiocyanate in dry acetone to afford the respective isothiocyanates as intermediates. The latter were treated in situ with 1,2- and 1, [...] 4-diaminobenzene, respectively, to afford the title compounds in high yields. A total of sixteen new compounds are reported herein. The structures of the products were confirmed by spectroscopic techniques (IR, ¹H and 13C NMR, mass spectrometry), elemental analysis and in case of 1d, by X-ray diffraction technique. All the synthesized compounds were also subjected to antibacterial bioevaluation against ten different Gram-positive and Gram-negative bacterial strains using levofloxacin as the standard drug and were shown to possess promising activities.

  20. Aryl Hydrocarbon Receptor Nuclear Translocator in Hepatocytes Is Required for Aryl Hydrocarbon Receptor–Mediated Adaptive and Toxic Responses in Liver

    OpenAIRE

    Nukaya, Manabu; Walisser, Jacqueline A.; Moran, Susan M.; Kennedy, Gregory D.; Bradfield, Christopher A.

    2010-01-01

    The aryl hydrocarbon receptor (AHR) plays a central role in the toxic responses to halogenated dibenzo-p-dioxins (“dioxins”), in the metabolic adaptation to polycyclic aromatic hydrocarbons, and in the development of the mature vascular system. A number of lines of evidence support the idea that the regulation of adaptive metabolism requires an AHR partnership with the aryl hydrocarbon receptor nuclear translocator (ARNT). Yet, for AHR-dependent vascular development and dioxin toxicity, t...

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

    OpenAIRE

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Synthesis of 3-(3-Aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazines That Have Antibacterial Activity and Also Inhibit Inorganic Pyrophosphatase

    OpenAIRE

    Lv, Wei; Banerjee, Biplab; Molland, Katrina L.; Seleem, Mohamed N.; Ghafoor, Adil; Hamed, Maha I.; Wan, Baojie; Franzblau, Scott G.; Mesecar, Andrew D.; Cushman, Mark

    2013-01-01

    Inorganic pyrophosphatases are potential targets for the development of novel antibacterial agents. A pyrophosphatase-coupled high-throughput screening assay intended to detect o-succinyl benzoic acid coenzyme A (OSB CoA) inhibitors led to the unexpected discovery of a new series of novel inorganic pyrophosphatase inhibitors. Lead optimization studies resulted in a series of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazine derivatives that were prepared by an efficient synthetic pathway. One ...

  4. A New Method for Production of Chiral 2-Aryl-2-fluoropropanoic Acids Using an Effective Kinetic Resolution of Racemic 2-Aryl-2-fluoropropanoic Acids

    OpenAIRE

    Atsushi Tengeiji; Isamu Shiina

    2012-01-01

    We report a new method for the preparation of chiral 2-aryl-2-fluoropropanoic acids, including 2-fluoroibuprofen, a fluorinated analogue of non-steroidal anti-inflammatory drugs (NSAIDs), by the kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids using enantioselective esterification. By applying pivalic anhydride (Piv2O) as a coupling agent, bis(?-naphthyl)methanol [(?-Np)2CHOH] as an achiral a...

  5. 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

    OpenAIRE

    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 ?-Heamolytic streptococcus, M. luteus, Klebsiella pneumonia, Microsporum gypseum, 9 against Staphylococcus aureus, Shigella flexneri, Vibreo cholerae, Pseudomonas aeruginosa, Aspergillus flavus, Mucor indicus,...

  6. Cyprodinil as an activator of aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Highlights: ? Cyprodinil activated the aryl hydrocarbon receptor (AHR). ? Cyprodinil induced nuclear translocation of the AHR, and the expression of CYP1A1. ? Cyprodinil enhanced dexamethasone-induced gene expression. ? Cyprodinil phosphorylated ERK, indicating its deregulation of ERK activity. -- Abstract: Cyprodinil is a pyrimidinamine fungicide, used worldwide by agriculture. It is used to protect fruit plants and vegetables from a wide range of pathogens. Benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are toxic environmental pollutants and are prototypes of aryl hydrocarbon receptor (AHR) ligands. Although the structure of cyprodinil distinctly differs from those of BaP and TCDD, our results show that cyprodinil induced nuclear translocation of the AHR, and induced the transcriptional activity of aryl hydrocarbon response element (AHRE). Cyprodinil induced the expression of cytochrome P450 (CYP) 1A1, a well-known AHR-targeted gene, in ovarian granulosa cells, HO23, and hepatoma cells, Hepa-1c1c7. Its induction did not appear in AHR signal-deficient cells, and was blocked by the AHR antagonist, CH-223191. Cyprodinil decreased AHR expression in HO23 cells, resulting in CYP1A1 expression decreasing after it peaked at 9 h of treatment in HO23 cells. Dexamethasone is a synthetic agonist of glucocorticoids. Cyprodinil enhanced dexamethasone-induced gene expression, and conversely, its induction of CYP1A1 expression was decreased by dexamethasone in HO23 cells, indicating its induction of crosstalk between the AHR and glucocorticoid receptor and its role as a potential endocrine disrupter. In addition to BaP, TCDD, and an AHR agonist, ?-NF, cyprodinil also phosphorylated extracellular signal-regulated kinase (ERK) in HO23 and Hepa-1c1c7 cells, indicating its deregulation of ERK activity. In summary, our results demonstrate that cyprodinil, similar to BaP, acts as an AHR activator, a potential endocrine disrupter, and an ERK disrupter

  7. A ligand for the aryl hydrocarbon receptor isolated from lung

    OpenAIRE

    Song, Jiasheng; Clagett-dame, Margaret; Peterson, Richard E.; Hahn, Mark E.; Westler, William M.; Sicinski, Rafal R.; Deluca, Hector F.

    2002-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is best known because it mediates the actions of polycyclic and halogenated aromatic hydrocarbon environmental toxicants such as 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. We report here the successful identification of an endogenous ligand for this receptor; ?20 ?g was isolated in pure form from 35 kg of porcine lung. Its structure was deduced as 2-(1?H-indole-3?-carbonyl)-thiazole-4...

  8. Monoamine oxidase inhibitory activity of 2-aryl-4H-chromen-4-ones.

    Science.gov (United States)

    Nayak, Badavath Vishnu; Ciftci-Yabanoglu, S; Bhakat, Soumendranath; Timiri, Ajay Kumar; Sinha, Barij N; Ucar, G; Soliman, Mahmoud E S; Jayaprakash, Venkatesan

    2015-02-01

    A series of twenty 2-aryl-4H-chromen-4-one (flavones) derivatives (3a-3s) were synthesized and tested for hMAO inhibitory activity. Fifteen compounds (3a, 3c, 3e-3h, 3j-3p, 3r, 3s) were found to be selective towards MAO-B, while 3d was selective towards MAO-A, and 3b, 3i and 3q were non-selective. Experimental Selectivity Index for MAO-B ranges from 2.0 (3g, 3p) to 30.0 (3j). Compound 3j, which is carrying 3,4-di-OMeC6H3 groups at R position on the molecule, was found to be potent MAO-B inhibitor amongst the fifteen with Ki value for MAO-B of 0.16±0.01 ?M comparable to that of standard drug, Selegiline (Ki for MAO-B is 0.16±0.01 ?M). Compound 3j also appeared as the most selective MAO-B inhibitor according to its best selectivity index (30.0), which is comparable to that of Selegiline (SIMAO-B=35.0). Molecular docking and molecular dynamics simulation studies were carried out using Autodock-4.0 and Amber12 to understand the molecular level interaction and energy relation of MAO isoforms with selective inhibitors (3d and 3j). Simulation results are in good agreement with the experimental results. Leads identified may further be explored to develop potent isoform specific inhibitors of MAO. PMID:25506816

  9. Microwave-assisted efficient synthesis of 2-hydroxydeoxybenzoins from the alkali degradation of readily prepared 3-aryl-4-hydroxycoumarins in water.

    Science.gov (United States)

    Zhou, Zhong-Zhen; Yan, Guang-Hua; Chen, Wen-Hua; Yang, Xue-Mei

    2013-01-01

    This paper describes an operationally simple, green and efficient approach for the synthesis of 2-hydroxydeoxybenzoins bearing diverse substituents from the microwave-assisted alkali degradation of 3-aryl-4-hydroxycoumarins in water. The latter compounds were readily prepared from the intramolecular Claisen condensation reaction of methyl 2-(2-arylacetoxy)benzoates in the presence of Cs2CO3-acetone, in excellent yields and without laborious workup procedures. This method is highly atom-economic and thus applicable for the large-scale synthesis of 2-hydroxydeoxybenzoins. PMID:24189303

  10. Tuning reactivity and site selectivity of simple arenes in C-H activation: ortho-arylation of anisoles via arene-metal ?-complexation.

    Science.gov (United States)

    Ricci, Paolo; Krämer, Katrina; Larrosa, Igor

    2014-12-31

    Current approaches to achieve site selectivity in the C-H activation of arenes involve the use of directing groups or highly electron-poor arenes. In contrast, simple arenes, such as anisole, are characterized by poor reactivity and selectivity. We report that ?-complexation to a Cr(CO)3 unit enhances the reactivity of anisoles providing an unprecedented ortho-selective arylation. This mild methodology can be used for the late stage functionalization of bioactive compounds containing the anisole motif, allowing the construction of novel organic scaffolds with few synthetic steps. PMID:25510851

  11. Cytotoxicity and topoisomerase I/II inhibition activity of novel 4-aryl/alkyl-1-(piperidin-4-yl)-carbonylthiosemicarbazides and 4-benzoylthiosemicarbazides.

    Science.gov (United States)

    Siwek, Agata; Bielawska, Anna; Maciorkowska, Elzbieta; Lepiarczyk, Monika; Bielawski, Krzysztof; Trotsko, Nazar; Wujec, Monika

    2014-04-01

    A series of eight thiosemicarbazide derivatives was examined for cytotoxicity in breast cancer cell cultures. Among them, 4-benzoylthiosemicarbazides proved to be only slightly less potent than chlorambucil in both MDA-MB-231 and MCF-7 lines. In contrast, 4-aryl/alkylthiosemicarbazides revealed significantly lower cytotoxicity effect. Subsequently, all titled compounds were tested as potential human topoisomerase I and II (topo I and topo II) inhibitors. Mechanistic studies revealed that tested thiosemicarbazides act as both topoisomerase I and topoisomerase II inhibitors. Among them, the best inhibitory activity was found for 4-benzoylthiosemicarbazides (1 and 2) with IC50 at 50 µM against topo II. PMID:23432612

  12. Biaryl synthesis by ring-opening Friedel-Crafts arylation of 1,4-epoxy-1,4-dihydronaphthalenes catalyzed by iron trichloride.

    Science.gov (United States)

    Sawama, Yoshinari; Asai, Shota; Kawajiri, Takahiro; Monguchi, Yasunari; Sajiki, Hironao

    2015-01-26

    Biaryl and heterobiaryl compounds are important frameworks across a range of fields including pharmaceutical and functional material chemistries. We have accomplished the efficient synthesis of various naphthalene-linked arenes and heteroarenes as biaryls and heterobiaryls by the FeCl3 -catalyzed Friedel-Crafts reactions accompanied by the ring-opening of the 1,4-epoxy moiety of 1,4-epoxy-1,4-dihydronaphthalenes. Especially, it is noteworthy that 1-silylated substrates were regioselectively transformed to the 3-aryl-1-silylnaphthalenes and the double Friedel-Crafts reactions using thiophene derivatives could directly produce the corresponding bis-naphthlated thiophene derivatives. PMID:25469749

  13. Design, synthesis and pharmacological evaluation of N-[4-(4-(alkyl/aryl/heteroaryl)-piperazin-1-yl)-phenyl]-carbamic acid ethyl ester derivatives as novel anticonvulsant agents.

    Science.gov (United States)

    Kumari, Shikha; Mishra, Chandra Bhushan; Tiwari, Manisha

    2015-03-01

    A series of alkyl/aryl/heteroaryl piperazine derivatives (37-54) were designed and synthesized as potential anticonvulsant agents. The target compounds are endowed with satisfactory physicochemical as well as pharmacokinetic properties. The synthesized compounds were screened for their in vivo anticonvulsant activity in maximal electroshock (MES) and subcutaneous pentylenetetrazole (sc-PTZ) seizure tests. Further, neurotoxicity evaluation was carried out using rotarod method. Structure activity relationship studies showed that compounds possessing aromatic group at the piperazine ring displayed potent anticonvulsant activity. Majority of the compounds showed anti-MES activity whereas compounds 39, 41, 42, 43, 44, 50, 52, and 53 exhibited anticonvulsant activity in both seizure tests. All the compounds except 42, 46, 47, and 50 did not show neurotoxicity. The most active derivative, 45 demonstrated potent anticonvulsant activity in MES test at the dose of 30mg/kg (0.5h) and 100mg/kg (4h) and also delivered excellent protection in sc-PTZ test (100mg/kg) at both time intervals. Therefore, compound 45 was further assessed in PTZ-kindling model of epilepsy which is widely used model for studying epileptogenesis. This compound was effective in delaying onset of PTZ-evoked seizures at the dose of 5mg/kg in kindled animals and significantly reduced oxidative stress better than standard drug phenobarbital (PB). In result, compound 45 emerged as a most potent and safer anticonvulsant lead molecule. PMID:25619635

  14. Fine-tuning the nucleophilic reactivities of boron ate complexes derived from aryl and heteroaryl boronic esters.

    Science.gov (United States)

    Berionni, Guillaume; Leonov, Artem I; Mayer, Peter; Ofial, Armin R; Mayr, Herbert

    2015-02-23

    Boron ate complexes derived from thienyl and furyl boronic esters and aryllithium compounds have been isolated and characterized by X-ray crystallography. Products and mechanisms of their reactions with carbenium and iminium ions have been analyzed. Kinetics of these reactions were monitored by UV/Vis spectroscopy, and the influence of the aryl substituents, the diol ligands (pinacol, ethylene glycol, neopentyl glycol, catechol), and the counterions on the nucleophilic reactivity of the boron ate complexes were examined. A Hammett correlation confirmed the polar nature of their reactions with benzhydrylium ions, and the correlation lg?k(20?°C)=sN (E+N) was employed to determine the nucleophilicities of the boron ate complexes and to compare them with those of other borates and boronates. The neopentyl and ethylene glycol derivatives were found to be 10(4) times more reactive than the pinacol and catechol derivatives. PMID:25604646

  15. Efficient (11)C-Carbonylation of Isolated Aryl Palladium Complexes for PET: Application to Challenging Radiopharmaceutical Synthesis.

    Science.gov (United States)

    Andersen, Thomas L; Friis, Stig D; Audrain, Hélène; Nordeman, Patrik; Antoni, Gunnar; Skrydstrup, Troels

    2015-02-01

    We describe the successful implementation of palladium-aryl oxidative addition complexes as stoichiometric reagents in carbonylation reactions with (11)CO to produce structurally challenging, pharmaceutically relevant compounds. This method enables the first (11)C-carbonyl labeling of an approved PET tracer, [(11)C]raclopride, for the dopamine D2/D3 receptor by carbonylation with excellent radiochemical purity and yield. Two other molecules, [(11)C]olaparib and [(11)C]JNJ 31020028, were efficiently labeled in this manner. The technique distinguishes itself from existing methods by the markedly improved purity profiles of the tracer molecules produced and provides access to complex structures in synthetically useful yields, hereby offering a viable alternative to other (11)C-labeling strategies. PMID:25569730

  16. Pd-catalyzed aerobic oxidative coupling of arenes: evidence for transmetalation between two Pd(II)-aryl intermediates.

    Science.gov (United States)

    Wang, Dian; Izawa, Yusuke; Stahl, Shannon S

    2014-07-16

    Pd-catalyzed aerobic oxidative coupling of arenes provides efficient access to biaryl compounds. The biaryl product forms via C-H activation of two arenes to afford a Pd(II)ArAr' intermediate, which then undergoes C-C reductive elimination. The key Pd(II)ArAr' intermediate could form via a "monometallic" pathway involving sequential C-H activation at a single Pd(II) center, or via a "bimetallic" pathway involving parallel C-H activation at separate Pd(II) centers, followed by a transmetalation step between two Pd(II)-aryl intermediates. Here, we investigate the oxidative coupling of o-xylene catalyzed by a PdX2/2-fluoropyridine catalyst (X = trifluoroacetate, acetate). Kinetic studies, H/D exchange experiments, and kinetic isotope effects provide clear support for a bimetallic/transmetalation mechanism. PMID:24965384

  17. Direct palladium-catalyzed C-4 arylation of tri-substituted furans with aryl chlorides: An efficient access to heteroaromatics

    International Nuclear Information System (INIS)

    A series of functionalized furans were synthesized by way of a palladium -catalyzed coupling reaction of 2,3,5-tri substituted furans with aryl chlorides through C-H bond cleavages at C-4 position. The feature of the reaction was facilitative preparation of furan derivatives with good functional group tolerance. All reactions gave the desired products in moderate to good yields in the presences of BuAd2P and t-BuOK in DMF at 120 .deg. C after 15 h

  18. Direct palladium-catalyzed C-4 arylation of tri-substituted furans with aryl chlorides: An efficient access to heteroaromatics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hai; Zeng, Jian; Liu, Huajie; Yi, Bing [College of Chemistry and Chemical Engineering/Hunan Institute of Engineering, Xiangtan (China); Zheng, Zhishuo [Guangdong Univ. of Education, Guangzhou (Korea, Republic of)

    2012-04-15

    A series of functionalized furans were synthesized by way of a palladium -catalyzed coupling reaction of 2,3,5-tri substituted furans with aryl chlorides through C-H bond cleavages at C-4 position. The feature of the reaction was facilitative preparation of furan derivatives with good functional group tolerance. All reactions gave the desired products in moderate to good yields in the presences of BuAd{sub 2}P and t-BuOK in DMF at 120 .deg. C after 15 h.

  19. Generation of detectable singlet aryl cations by photodehalogenation of fluoroquinolones.

    Science.gov (United States)

    Cuquerella, M Consuelo; Miranda, Miguel A; Bosca, Francisco

    2006-04-01

    Nanosecond laser flash photolysis (lambdaexc = 355 nm) of neutral aqueous solutions of lomefloxacin (LFX, a 8-fluorinated 7-amino-4-quinolone-3-carboxylic acid derivative) produces a detectable transient species, which shows an absorption maximum at 490 nm and can be assigned to an aryl cation. This intermediate has a lifetime of ca. 200 ns in net water, reacts with Br- and Cl- with rate constants of 3.6 x 10(9) M(-1) s(-1) and 4.1 x 10(8) M(-1) s(-1), respectively, and shows a lack of reactivity toward molecular oxygen. From the photolysis of BAY y3118 (BAY, a 8-chlorinated analogue), an aryl cation is also generated, showing absorption maximum at 480 nm (lifetime of ca. 1 micros in net water) and a reaction rate constant of 9 x 10(9) M(-1) s(-1) with Br(-). The existence of these highly reactive species arising from direct photolysis of LFX and BAY can justify the photogenotoxic properties associated with these antibacterial drugs likely due to direct reaction of their cations with DNA. PMID:16570937

  20. Silicon dioxide surfaces with aryl interaction sites for chromatographic applications

    Energy Technology Data Exchange (ETDEWEB)

    Gadzal-Kopciuch, R.; Kluska, M.; Welniak, M.; Buszewski, B

    2005-02-15

    The paper presents the results of a study on aryl phases aimed at the increase of the separation selectivity of substances containing {pi} electrons, and improving the reproducibility of retention data. The above phases contain not only a carbon chain of a different length, linking them to the support, but also one or two aromatic rings. The suitability of the newly obtained packings for the purposes of high-performance liquid chromatography was verified on the basis of a description of surface topography before and after the modification process. Various physicochemical methods were employed to determine the effectiveness of chemical modification, i.e., elemental analysis, infrared spectroscopy, and nuclear magnetic resonance. The aryl packings obtained were used for the separation of polynuclear aromatic hydrocarbons and budesonide epimers, tested under hydroorganic conditions (water/ethanol, water/methanol, water/acetonitrile). The application of a methanol/water mobile phase and a new-generation naphthylpropyl stationary phase for the separation of the 22R and 22S diastereoisomers of budesonide allowed the obtention of reproducible results and make qualitative and quantitative determinations of particular enantiomers.

  1. Silicon dioxide surfaces with aryl interaction sites for chromatographic applications

    International Nuclear Information System (INIS)

    The paper presents the results of a study on aryl phases aimed at the increase of the separation selectivity of substances containing ? electrons, and improving the reproducibility of retention data. The above phases contain not only a carbon chain of a different length, linking them to the support, but also one or two aromatic rings. The suitability of the newly obtained packings for the purposes of high-performance liquid chromatography was verified on the basis of a description of surface topography before and after the modification process. Various physicochemical methods were employed to determine the effectiveness of chemical modification, i.e., elemental analysis, infrared spectroscopy, and nuclear magnetic resonance. The aryl packings obtained were used for the separation of polynuclear aromatic hydrocarbons and budesonide epimers, tested under hydroorganic conditions (water/ethanol, water/methanol, water/acetonitrile). The application of a methanol/water mobile phase and a new-generation naphthylpropyl stationary phase for the separation of the 22R and 22S diastereoisomers of budesonide allowed the obtention of reproducible results and make qualitative and quantitative determinations of particular enantiomers

  2. Effects of perfluoroalkyl acids on the function of the thyroid hormone and the aryl hydrocarbon receptor

    DEFF Research Database (Denmark)

    Long, Manhai; Ghisari, Mandana

    2013-01-01

    Perfluoroalkyl acids (PFAAs) are perfluorinated compounds that widely exist in the environment and can elicit adverse effects including endocrine disruption in humans and animals. This study investigated the effect of seven PFAAs on the thyroid hormone (TH) system assessing the proliferation of the 3,3',5-triiodo-L-thryonine (T3)-dependent rat pituitary GH3 cells using the T-screen assay and the effect on the aryl hydrocarbon receptor (AhR) transactivation in the AhR-luciferase reporter gene bioassay. A dose-dependent impact on GH3 cells was observed in the range 1?×?10(-9)-1?×?10(-4) M: seven PFAAs (perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorododecanoic acid (PFDoA)) inhibited the GH3 cell growth, and four PFAAs (PFOS, PFHxS, PFNA, and PFUnA) antagonized the T3-induced GH3 cell proliferation. At the highest test concentration, PFHxS showed a further increase of the T3-induced GH3 growth. Among the seven tested PFAAs, only PFDoA and PFDA elicited an activating effect on the AhR. In conclusion, PFAAs possess in vitro endocrine-disrupting potential by interfering with TH and AhR functions, which need to be taken into consideration when assessing the impact on human health.

  3. Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway.

    Science.gov (United States)

    Gondouin, Bertrand; Cerini, Claire; Dou, Laetitia; Sallée, Marion; Duval-Sabatier, Ariane; Pletinck, Anneleen; Calaf, Raymond; Lacroix, Romaric; Jourde-Chiche, Noémie; Poitevin, Stéphane; Arnaud, Laurent; Vanholder, Raymond; Brunet, Philippe; Dignat-George, Françoise; Burtey, Stéphane

    2013-10-01

    In chronic kidney disease (CKD), uremic solutes accumulate in blood and tissues. These compounds probably contribute to the marked increase in cardiovascular risk during the progression of CKD. The uremic solutes indoxyl sulfate and indole-3-acetic acid (IAA) are particularly deleterious for endothelial cells. Here we performed microarray and comparative PCR analyses to identify genes in endothelial cells targeted by these two uremic solutes. We found an increase in endothelial expression of tissue factor in response to indoxyl sulfate and IAA and upregulation of eight genes regulated by the transcription factor aryl hydrocarbon receptor (AHR). The suggestion by microarray analysis of an involvement of AHR in tissue factor production was confirmed by siRNA inhibition and the indirect AHR inhibitor geldanamycin. These observations were extended to peripheral blood mononuclear cells. Tissue factor expression and activity were also increased by AHR agonist dioxin. Finally, we measured circulating tissue factor concentration and activity in healthy control subjects and in patients with CKD (stages 3-5d), and found that each was elevated in patients with CKD. Circulating tissue factor levels were positively correlated with plasma indoxyl sulfate and IAA. Thus, indolic uremic solutes increase tissue factor production in endothelial and peripheral blood mononuclear cells by AHR activation, evoking a 'dioxin-like' effect. This newly described mechanism of uremic solute toxicity may help understand the high cardiovascular risk of CKD patients. PMID:23636172

  4. The Aryl Hydrocarbon Receptor Meets Immunology: Friend or Foe? A Little of Both

    Science.gov (United States)

    Julliard, Walker; Fechner, John H.; Mezrich, Joshua D.

    2014-01-01

    The aryl hydrocarbon receptor (AHR) has long been studied by toxicologists as a ligand-activated transcription factor that is activated by dioxin and other environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs). The hallmark of AHR activation is the upregulation of the cytochrome P450 enzymes that metabolize many of these toxic compounds. However, recent findings demonstrate that both exogenous and endogenous AHR ligands can alter innate and adaptive immune responses including effects on T-cell differentiation. Kynurenine, a tryptophan breakdown product, is one such endogenous ligand of the AHR. Expression of indoleamine 2,3-dioxygenase by dendritic cells causes accumulation of kynurenine and results in subsequent tolerogenic effects including increased regulatory T-cell activity. At the same time, PAHs found in pollution enhance Th17 differentiation in the lungs of exposed mice via the AHR. In this perspective, we will discuss the importance of the AHR in the immune system and the role this might play in normal physiology and response to disease. PMID:25324842

  5. Spectral and catalytic properties of aryl-alcohol oxidase, a fungal flavoenzyme acting on polyunsaturated alcohols.

    Science.gov (United States)

    Ferreira, Patricia; Medina, Milagros; Guillén, Francisco; Martínez, María Jesús; Van Berkel, Willem J H; Martínez, Angel T

    2005-08-01

    Spectral and catalytic properties of the flavoenzyme AAO (aryl-alcohol oxidase) from Pleurotus eryngii were investigated using recombinant enzyme. Unlike most flavoprotein oxidases, AAO does not thermodynamically stabilize a flavin semiquinone radical and forms no sulphite adduct. AAO catalyses the oxidative dehydrogenation of a wide range of unsaturated primary alcohols with hydrogen peroxide production. This differentiates the enzyme from VAO (vanillyl-alcohol oxidase), which is specific for phenolic compounds. Moreover, AAO is optimally active in the pH range of 5-6, whereas VAO has an optimum at pH 10. Kinetic studies showed that AAO is most active with p-anisyl alcohol and 2,4-hexadien-1-ol. AAO converts m- and p-chlorinated benzyl alcohols at a similar rate as it does benzyl alcohol, but introduction of a p-methoxy substituent in benzyl alcohol increases the reaction rate approx. 5-fold. AAO also exhibits low activity on aromatic aldehydes. 19F NMR analysis showed that fluorinated benzaldehydes are converted into the corresponding benzoic acids. Inhibition studies revealed that the AAO active site can bind a wide range of aromatic ligands, chavicol (4-allylphenol) and p-anisic (4-methoxybenzoic) acid being the best competitive inhibitors. Uncompetitive inhibition was observed with 4-methoxybenzylamine. The properties described above render AAO a unique oxidase. The possible mechanism of AAO binding and oxidation of substrates is discussed in the light of the results of the inhibition and kinetic studies. PMID:15813702

  6. Induction of oxidative stress responses by dioxin and other ligands of the aryl hydrocarbon receptor.

    Science.gov (United States)

    Reichard, John F; Dalton, Timothy P; Shertzer, Howard G; Puga, Alvaro

    2005-01-01

    TCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl hydrocarbon receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic in either bacteria or most in vitro assay systems. They do so in spite of having repeatedly been linked to oxidative stress and to mutagenic and carcinogenic outcomes. Oxidative stress, on the other hand, has been used as a marker for the toxicity of dioxin and its congeners. We have focused this review on the connection between oxidative stress induction and the toxic effects of fetal and adult dioxin exposure, with emphasis on the large species difference in sensitivity to this agent. We examine the roles that the dioxin-inducible cytochromes P450s play in the cellular and toxicological consequences of dioxin exposure with emphasis on oxidative stress involvement. Many components of the health consequences resulting from dioxin exposure may be attributable to epigenetic mechanisms arising from prolonged reactive oxygen generation. PMID:18648615

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

    International Nuclear Information System (INIS)

    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.

  8. Comparative Growth of Natural Bacterial Isolates on Various Lignin-Related Compounds

    OpenAIRE

    Gonzalez, B.; Merino, A.; Almeida, M.; Vicn?a, R.

    1986-01-01

    Bacterial strains were isolated on the basis of their ability to proliferate in a minimal medium containing one of a series of lignin-related compounds as the sole carbon and energy source. These included the aromatic monomers guaiacol, vanillic and coumaric acids, a dimer and a trimer possessing the arylglycerol-?-aryl ether linkage, anisoin, and both the ether-soluble and -insoluble fractions of kraft lignin. The growth of the strains on each of these compounds was measured. The results sh...

  9. Application of metalation reactions for synthesis of sulfur/selenium-containing heterocyclic compounds

    OpenAIRE

    Shirani, Hamid

    2009-01-01

    This thesis deals mainly with the synthesis of various sulfur/selenium-containing heterocyclic compounds, many of which include structural features present in several biologically active molecules, with particular emphasis on compounds of synthetic importance, such as indoles, as well as other heteroaromatic species. In the first part, an efficient procedure toward synthesis of new 3-(arylthio)indoles based on reactions of aryl Grignard reagents or lithiated heteroaromat...

  10. Transition-metal-catalyzed arylation of nitroimidazoles and further transformations of manipulable nitro group.

    Science.gov (United States)

    Iaroshenko, Viktor O; Gevorgyan, Ashot; Mkrtchyan, Satenik; Arakelyan, Knar; Grigoryan, Tatevik; Yedoyan, Julietta; Villinger, Alexander; Langer, Peter

    2015-02-20

    Pd- or Ni-catalyzed C-H arylation of 4-nitroimidazole derivatives directed by a manipulable nitro group was developed. The reaction tolerates a wide range of substituted aryl halides and 4-nitroimidazoles. The experiments indicated that the nitro group has influence on regioselectivity of the reaction. In addition, we have shown that the efficiency of the Suzuki-Miyaura cross-coupling reaction of nitroimidazoles is slightly lower in comparison to the direct C-H arylation. The exploration of the chemical potential of the nitro group and a putative reaction mechanism are discussed. PMID:25614963

  11. Enantioselective Cross-Coupling of meso-Epoxides with Aryl Halides.

    Science.gov (United States)

    Zhao, Yang; Weix, Daniel J

    2015-03-11

    The first enantioselective cross-electrophile coupling of aryl bromides with meso-epoxides to form trans-?-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

  12. The direct catalytic enantioselective synthesis of protected aryl beta-hydroxy-alpha-amino acids.

    OpenAIRE

    Willis, Mc; Cutting, Ga; Piccio, Vj; Durbin, Mj; John, Mp

    2005-01-01

    The combination of three reagents-a tridentate pybox ligand (pybox = pyridine bis(oxazoline)), magnesium perchlorate, and Hünig base (iPr 2EtN)-allows the catalytic generation of a chiral glycine enolate from 1 that undergoes highly enantioselective addition to a range of aryl aldehydes 2. The protected aryl ?-hydroxy-?-amino acid products obtained include a protected version of one of the aryl serine units present in the glycopeptide antibiotic vancomycin. © 2005 Wiley-VCH Verlag GmbH an...

  13. Mild palladium-catalyzed cyanation of (hetero)aryl halides and triflates in aqueous media.

    Science.gov (United States)

    Cohen, Daniel T; Buchwald, Stephen L

    2015-01-16

    A mild, efficient, and low-temperature palladium-catalyzed cyanation of (hetero)aryl halides and triflates is reported. Previous palladium-catalyzed cyanations of (hetero)aryl halides have required higher temperatures to achieve good catalytic activity. This current reaction allows the cyanation of a general scope of (hetero)aryl halides and triflates at 2-5 mol % catalyst loadings with temperatures ranging from rt to 40 °C. This mild method was applied to the synthesis of lersivirine, a reverse transcriptase inhibitor. PMID:25555140

  14. Evolution of a fourth generation catalyst for the amination and thioetherification of aryl halides.

    Science.gov (United States)

    Hartwig, John F

    2008-11-18

    Many active pharmaceuticals, herbicides, conducting polymers, and components of organic light-emitting diodes contain arylamines. For many years, this class of compound was prepared via classical methods, such as nitration, reduction and reductive alkylation, copper-mediated chemistry at high temperatures, addition to benzyne intermediates, or direct nucleophilic substitution on particularly electron-poor aromatic or heteroaromatic halides. However, during the past decade, palladium-catalyzed coupling reactions of amines with aryl halides have largely supplanted these earlier methods. Successive generations of catalysts have gradually improved the scope and efficiency of the palladium-catalyzed reaction. This Account describes the conceptual basis and utility of our latest, "fourth-generation" palladium catalyst for the coupling of amines and related reagents with aryl halides. In the past five years, we have developed these catalysts using the lessons learned from previous generations of catalysts developed in our group and in other laboratories. The ligands on the fourth-generation catalyst combine the chelating properties of the aromatic bisphosphines of the second-generation systems with the steric properties and strong electron donation of the hindered alkylphosphines of the third-generation systems. The currently most reactive catalyst in this class is generated from palladium and a sterically hindered version of the Josiphos family of ligands that possesses a ferrocenyl-1-ethyl backbone, a hindered di-tert-butylphosphino group, and a hindered dicyclohexylphosphino group. This system catalyzes the coupling of aryl chlorides, bromides, and iodides with primary amines, N-H imines, and hydrazones in high yield. The reaction has broad scope, high functional group tolerance, and nearly perfect selectivity for monoarylation. It also requires the lowest levels of palladium that have been used for C-N coupling. In addition, this latest catalyst has dramatically improved the coupling of thiols with haloarenes to form C-S bonds. Using ligands that lacked one or more of the structural elements of the most active catalyst, we examined the effects of individual structural elements of the Josiphos ligand on catalyst activity. This set of studies showed that each one of these elements contributes to the high reactivity and selectivity of the catalyst containing the hindered, bidentate Josiphos ligand. Finally, we examined the effect of electronic properties on the rates of reductive elimination to distinguish between the effect of the properties of the M-N sigma-bond and the nitrogen electron pair. We have found that the effects of electronic properties on C-C and C-N bond-forming reductive elimination are similar. Because the amido ligands contain an electron pair, while the alkyl ligands do not, we have concluded that the major electronic effect is transmitted through the sigma-bond. PMID:18681463

  15. Characterization of polycyclic aromatic compounds in diesel exhaust particulate extract responsible for aryl hydrocarbon receptor activity

    Science.gov (United States)

    Soontjens, Carol D.; Holmberg, Kristina; Westerholm, Roger N.; Rafter, Joseph J.

    Chemical fractions of a model diesel exhaust particulate extract, notably the fraction containing polycyclic aromatic hydrocarbons (PAH) (Fraction II), mono-nitro PAH (Fraction III), and dinitro-PAH (Fraction IV) have been shown to displace binding of 2,3,7,8-tetrachloro[1,6-[ 3H

  16. Copper-catalyzed nitrogen loss of sulfonylhydrazones: a reductive strategy for the synthesis of sulfones from carbonyl compounds.

    Science.gov (United States)

    Feng, Xing-Wen; Wang, Jian; Zhang, Ji; Yang, Jing; Wang, Na; Yu, Xiao-Qi

    2010-10-01

    An efficient method for the synthesis of sulfones via nitrogen loss of sulfonyl hydrazones is described. The reaction was performed in the presence of simple copper salt and base by utilization of sulfonyl hydrazones, which were easily prepared from carbonyl compounds. A wide variety of aryl and alkyl sulfones were obtained in moderate to good yields. PMID:20812669

  17. Cu-Catalyzed Aerobic Oxidative Cyclizations of 3-N-Hydroxyamino-1,2-propadienes with Alcohols, Thiols, and Amines To Form ?-O-, S-, and N-Substituted 4-Methylquinoline Derivatives.

    Science.gov (United States)

    Sharma, Pankaj; Liu, Rai-Shung

    2015-03-16

    A one-pot, two-step synthesis of ?-O-, S-, and N-substituted 4-methylquinoline derivatives through Cu-catalyzed aerobic oxidations of N-hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N-hydroxyaminoallenes with NuH (Nu=OH, OR, NHR, and SR) to form 3-substituted 2-en-1-ones, followed by Brønsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical-type mechanism rather than a typical nitrone-intermediate route. The utility of this new Cu-catalyzed reaction is shown by its applicability to the synthesis of several 2-amino-4-methylquinoline derivatives, which are known to be key precursors to several bioactive molecules. PMID:25657028

  18. Oxidative Aromatization, Cytotoxic Activity Evaluation and Conformational Study of Novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8(9H, 12H)-dione Derivatives.

    Science.gov (United States)

    Motamedi, Radineh; Shafiee, Abbas; Rezai, Mohammad Reza; Firuzi, Omidreza; Edraki, Najmeh; Miri, Ramin

    2014-01-01

    In the present work, novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8(9H, 12H)-dione derivatives were synthesized by oxidation of 7-aryl-8, 9, 10, 12-tetrahydro-7H-chromeno[4, 3-b]quinoline-6, 8-diones in the presence of silica sulfuric acid/NaNO2 with yields of 64-74%. Cytotoxic activity of synthesized compounds was assessed on three different human cancer cell lines (K562, LS180, and MCF-7). Synthesized compounds showed moderate cytotoxic activities. The most active one apeared to be 2e, containing a methoxy group on the meta position of phenyl ring (IC50 range in different cell lines: 11.1-55.7 µM). Furthermore; comparison of the cytotoxic activity of these novel oxidized derivatives with non-oxidized counterparts revealed that oxidation of dihydropyridine ring to pyridine, improves the activity especially in LS180 cell line. Conformational analysis revealed that some conformational aspects of oxidized derivatives such as orientation of C7-aryl substitute were clearly different from non-oxidized ones. PMID:24734061

  19. Environmentally benign synthesis, molecular properties prediction and anti-inflammatory activity of novel isoxazolo[5,4-d]isoxazol-3-yl-aryl-methanones via vinylogous Henry nitroaldol adducts as synthons.

    Science.gov (United States)

    Rajanarendar, E; Rama Krishna, S; Nagaraju, D; Govardhan Reddy, K; Kishore, B; Reddy, Y N

    2015-04-01

    Synthesis of novel 6-methylisoxazolo[5,4-d]isoxazol-3-yl-aryl-methanones 5 has been achieved via nitro-nitrite rearrangement by utilizing vinylogous nitroaldol adducts as synthons under mild conditions. Furthermore, the new series of compounds 5a-i were assessed for molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) & MolSoft (MolSoft, 2007) softwares, lipophilicity and solubility parameters using ALOGPS 2.1 program. The new series of compounds 5a-i were screened for their anti-inflammatory activity. PMID:25708616

  20. A general method for palladium-catalyzed reactions of primary sulfonamides with aryl nonaflates.

    Science.gov (United States)

    Shekhar, Shashank; Dunn, Travis B; Kotecki, Brian J; Montavon, Donna K; Cullen, Steven C

    2011-06-01

    A general method for Pd-catalyzed sulfonamidation of aryl nonafluorobutanesulfonates (aryl nonaflates) is described. A biaryl phosphine ligand, t-BuXPhos, formed the most active catalyst, and K(3)PO(4) in tert-amyl alcohol was found to be the optimal base-solvent combination for the reaction. The reaction conditions were tolerant of various functional groups such as cyano, nitro, ester, aldehyde, ketone, chloride, carbamate, and phenol. Heterocyclic aryl nonaflates were found to be suitable coupling partners. High yields of the coupled products were obtained from the reactions between inherently disfavored substrates such as electron-rich nonaflates and electron-poor sulfonamides. Kinetic data suggest reductive elimination to be the rate-limiting step for the reaction. The only limitation of this methodology that we have identified is the inability of 2,6-disubstituted aryl nonaflates to efficiently participate in the reaction. PMID:21510695

  1. Aryl hydrocarbon receptor and estrogen receptor ligand activity of organic extracts from road dust and diesel exhaust particulates.

    Science.gov (United States)

    Misaki, Kentaro; Suzuki, Masato; Nakamura, Masafumi; Handa, Hiroshi; Iida, Mitsuru; Kato, Teruhisa; Matsui, Saburo; Matsuda, Tomonari

    2008-08-01

    A wide variety of contaminants derived from diesel and gasoline engines, tire, asphalt, and natural organic compounds is found in road dust. Polycyclic aromatic compounds (PACs) are the important toxic targets among various contents in road dust and diesel exhaust particulates (DEPs), and endocrine-disrupting activity of PACs was suggested. In the present study, aryl hydrocarbon receptor (AhR) ligand activity was confirmed in the extract of both road dust and DEPs. In the separation of the extracts for both road dust and DEPs with reversed-phase HPLC, it was found that polar fractions contributed to significant AhR ligand activity in both a mouse hepatoma (H1L1) cell system and a yeast system. Furthermore, the contribution of these polar fractions was higher in DEPs than in road dust, probably because of the greater concentration of oxy-PAHs in DEPs than in road dust. The contribution of contaminants associated with the polar region to AhR ligand activity was also evident following the separation of road dust with normal-phase HPLC. Additionally, remarkable estrogen receptor (ER) ligand activity was detected in the highly polar region separated with normal-phase HPLC. It is suggested that many unknown AhR or ER ligand active compounds are contained in the polar region. PMID:18180859

  2. Synthesis and Biological Evaluation of 3-Aryl-quinoxaline-2-carbonitrile 1,4-Di-N-oxide Derivatives as Hypoxic Selective Anti-tumor Agents

    Directory of Open Access Journals (Sweden)

    Yongzhou Hu

    2012-08-01

    Full Text Available A series of 3-aryl-2-quinoxaline-carbonitrile 1,4-di-N-oxide derivatives were designed, synthesized and evaluated for hypoxic and normoxic cytotoxic activity against human SMMC-7721, K562, KB, A549 and PC-3 cell lines. Many of these new compounds displayed more potent hypoxic cytotoxic activity compared with TX-402 and TPZ in the tumor cells based evaluation, which confirmed our hypothesis that the replacement of the 3-amine with the substituted aryl ring of TX-402 increases the hypoxic anti-tumor activity. The preliminary SAR revealed that 3-chloro was a favorable substituent in the phenyl ring for hypoxic cytotoxicity and 7-methyl or 7-methoxy substituted derivatives exhibited better hypoxic selectivity against most of the tested cell lines. The most potent compound, 7-methyl-3-(3-chlorophenyl-quinoxaline-2-carbonitrile 1,4-dioxide (9h was selected for further anti-tumor evaluation and mechanistic study. It also exhibited significant cytotoxic activity against BEL-7402, HepG2, HL-60, NCI-H460, HCT-116 and CHP126 cell lines in hypoxia with IC50 values ranging from 0.31 to 3.16 ?M, and preliminary mechanism study revealed that 9h induced apoptosis in a caspase-dependent pathway.

  3. Novel aryl ?-aminocarbonyl derivatives as inhibitors of Trypanosoma cruzi trypanothione reductase: binding mode revised by docking and GRIND2-based 3D-QSAR procedures.

    Science.gov (United States)

    de Paula da Silva, Carlos Henrique Tomich; Bernardes, Lílian Sibelle Campos; da Silva, Vinícius Barreto; Zani, Carlos Leomar; Carvalho, Ivone

    2012-01-01

    Trypanothione reductase has long been investigated as a promising target for chemotherapeutic intervention in Chagas disease, since it is an enzyme of a unique metabolic pathway that is exclusively present in the pathogen but not in the human host, which has the analog Glutathione reductase. In spite of the present data-set includes a small number of compounds, a combined use of flexible docking, pharmacophore perception, ligand binding site prediction, and Grid-Independent Descriptors GRIND2-based 3D-Quantitative Structure-Activity Relationships (QSAR) procedures allowed us to rationalize the different biological activities of a series of 11 aryl ?-aminocarbonyl derivatives, which are inhibitors of Trypanosoma cruzi trypanothione reductase (TcTR). Three QSAR models were built and validated using different alignments, which are based on docking with the TcTR crystal structure, pharmacophore, and molecular interaction fields. The high statistical significance of the models thus obtained assures the robustness of this second generation of GRIND descriptors here used, which were able to detect the most important residues of such enzyme for binding the aryl ?-aminocarbonyl derivatives, besides to rationalize distances among them. Finally, a revised binding mode has been proposed for our inhibitors and independently supported by the different methodologies here used, allowing further optimization of the lead compounds with such combined structure- and ligand-based approaches in the fight against the Chagas disease. PMID:22546000

  4. The palladium-catalyzed trifluoromethylation of aryl chlorides.

    Science.gov (United States)

    Cho, Eun Jin; Senecal, Todd D; Kinzel, Tom; Zhang, Yong; Watson, Donald A; Buchwald, Stephen L

    2010-06-25

    The trifluoromethyl group can dramatically influence the properties of organic molecules, thereby increasing their applicability as pharmaceuticals, agrochemicals, or building blocks for organic materials. Despite the importance of this substituent, no general method exists for its installment onto functionalized aromatic substrates. Current methods either require the use of harsh reaction conditions or suffer from a limited substrate scope. Here we report the palladium-catalyzed trifluoromethylation of aryl chlorides under mild conditions, allowing the transformation of a wide range of substrates, including heterocycles, in excellent yields. The process tolerates functional groups such as esters, amides, ethers, acetals, nitriles, and tertiary amines and, therefore, should be applicable to late-stage modifications of advanced intermediates. We have also prepared all the putative intermediates in the catalytic cycle and demonstrated their viability in the process. PMID:20576888

  5. Fluorescence characteristics of aryl boronic acid derivate (PBA)

    Science.gov (United States)

    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 (?g) and excited state (?e) 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 (??) 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.

  6. Two anionic [CuI6X7]nn- (X=Br and I) chain-based organic-inorganic hybrid solids with N-substituted benzotriazole ligands

    International Nuclear Information System (INIS)

    Solvothermal reactions of the flexible ligand 1,6-Bi(benzotriazole)hexane with CuI and KI or CuBr and KBr in ethanol generate two hybrid compounds, namely, {(HETA)[(Cu6I7)(ETA)2]}n(1) and {K(Cu6Br7)(BBTH)}n(2) (ETA=N-ethylbenzotriazole, HETA=protonated N-ethylbenzotriazole, BBTH=1,6-bi(benzotriazole)hexane). In 1, two [Cu3I4] vertex missing cubane-like subunits link each other by sharing one I atom to give a [Cu6I7] cluster, which further form novel 1D [Cu6I7]nn- anionic chain. Two in-situ generated ETA ligands finished the 4-coordinated environments of copper centers and another one discrete protonated ETA ligand keeps the charge neutrality for 1. In complex 2, bowl-shaped [Cu5Br4] clusters and rhomboid [Cu2Br2] dimers link each other to generate a [Cu6Br7]nn- 1D chain. BBTH ligands complete the tetrahedral spheres of Cu(I), and 7-coordinated K atoms further extend the 1D chain motifs to a 2D hybrid layer of 2. The UV-vis diffuse reflectance spectrum and luminescence measurements show that compound 1 and 2 both are potential semiconductor and photoluminescence materials. - Graphical abstract: Two unprecedented anionic [CuI6X7]nn- (X=Br and I) chain-based organic-in (X=Br and I) chain-based organic-inorganic hybrid solids, namely, {(HETA)[(Cu6I7)(ETA)2]}n (1) and {K(Cu6Br7)(BBTH)}n(2) (ETA=N-ethylbenzotriazole, HETA=protonated N-ethylbenzotriazole, BBTH=1,6-bi(benzotriazole)- hexane) have been synthesized under solvothermal reactions and characterized.

  7. Copper-catalyzed one-pot trifluoromethylation/aryl migration/carbonyl formation with homopropargylic alcohols.

    Science.gov (United States)

    Gao, Pin; Shen, Yong-Wen; Fang, Ran; Hao, Xin-Hua; Qiu, Zi-Hang; Yang, Fan; Yan, Xiao-Biao; Wang, Qiang; Gong, Xiang-Jun; Liu, Xue-Yuan; Liang, Yong-Min

    2014-07-14

    A novel copper-catalyzed one-pot functionalization of homopropargylic alcohols that involves trifluoromethylation, aryl migration, and formation of a carbonyl moiety has been developed. This reaction constitutes the first direct conversion of homopropargylic alcohols into CF3-containing 3-butenal or 3-buten-1-one derivatives in a regioselective manner. Mechanistic studies indicate that the 1,4-aryl migration proceeds through a radical pathway. PMID:24938432

  8. Unprecedentedly mild direct Pd-catalyzed arylation of oxazolo[4,5-b]pyridine

    DEFF Research Database (Denmark)

    Zhuravlev, Fedor

    2006-01-01

    Pd-catalyzed C-2 arylation of oxazolo[4,5-b]pyridine proceeds efficiently at 30 degrees C and tolerates a variety of aryl halides, including derivatized amino acids for which no racemization was observed during the reaction. Experimental evidence for facile deprotonation of oxazolo[4,5-b]pyridine under the reaction conditions is presented and the nature of the anionic intermediates is computationally examined. (c) 2006 Elsevier Ltd. All rights reserved.

  9. Synthesis and preliminary evaluation of antinociceptive activity of novel isoxazolyl-aryl-hydrazones

    International Nuclear Information System (INIS)

    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)

  10. Transition-metal-free arylations via photogenerated triplet 4-alkyl- and 4-trimethylsilylphenyl cations.

    Science.gov (United States)

    Qrareya, Hisham; Raviola, Carlotta; Protti, Stefano; Fagnoni, Maurizio; Albini, Angelo

    2013-06-21

    The irradiation in protic solvents of 4-chloroalkylbenzenes and 4-chlorophenyltrimethylsilane caused the heterolytic cleavage of aryl-chlorine bonds to give the corresponding triplet phenyl cations. These were exploited for transition-metal-free arylation reactions under mild conditions to give allylbenzenes, ?-benzyl lactones, 3-arylacetals (ketals), and biaryls in moderate to good yields. The path followed was supported by DFT calculations at the UB3LYP/6-311+G(2d,p) level. PMID:23688128

  11. Synthesis of Novel Aryl(heteroaryl)sulfonyl Ureas of Possible Biological Interest

    OpenAIRE

    Maria Gdaniec; Jaros?aw S?czewski; Karolina Lisewska; Agnieszka Kiedrowska; Marta ?obocka; Monika Samsel; Anna Kuchnio; Franciszek S?czewski; Bednarski, Patrick J.

    2010-01-01

    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 formatio...

  12. PEGylated Polyamidoamine Dendrimers with Bis-Aryl Hydrazone Linkages for Enhanced Gene Delivery

    OpenAIRE

    Yuan, Quan; Yeudall, W. Andrew; Yang, Hu

    2010-01-01

    Surface modification of polyamidoamine (PAMAM) dendrimers with polyethylene glycol (PEG) often results in the decrease in their buffering capacity, which is essential for gene transfer. In this work, bis-aryl hydrazone bond, which possesses protonatable pyridine and amines, was explored as a new linkage for PEGylation of PAMAM dendrimers. PEGylated polyamidoamine (PAMAM) dendrimer G4.0 conjugates with bis-aryl hydrazone (BAH) linkages were synthesized following a two-step procedure: activatio...

  13. Copper-catalyzed [18F]fluorination of (mesityl)(aryl)iodonium salts.

    Science.gov (United States)

    Ichiishi, Naoko; Brooks, Allen F; Topczewski, Joseph J; Rodnick, Melissa E; Sanford, Melanie S; Scott, Peter J H

    2014-06-20

    A practical, rapid, and highly regioselective Cu-catalyzed radiofluorination of (mesityl)(aryl)iodonium salts is described. This protocol utilizes [(18)F]KF to access (18)F-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-[(18)F]fluorophenylalanine and 6-[(18)F]fluoroDOPA. PMID:24890658

  14. Platinum oxide catalyzed silylation of aryl halides with triethylsilane: an efficient synthetic route to functionalized aryltriethylsilanes.

    Science.gov (United States)

    Hamze, Abdallah; Provot, Olivier; Alami, Mouâd; Brion, Jean-Daniel

    2006-03-01

    The first platinum-catalyzed selective silylation of aryl halides including aryl iodides and bromides having an electron-withdrawing group is described. The reaction takes place rapidly in NMP with triethylsilane as a silicon source and sodium acetate to provide functionalized aryltriethylsilanes in moderate to good yields. Heteroaromatic halides also were found to be readily silylated with triethylsilane. The procedure is chemoselective and tolerates a wide variety of functional groups. PMID:16494477

  15. Aryl(hydro)boranes: versatile building blocks for boron-doped ?-electron materials.

    Science.gov (United States)

    Lorbach, Andreas; Hübner, Alexander; Wagner, Matthias

    2012-05-28

    Boron-containing ?-conjugated molecules offer a substantial application potential in the field of organic electronics. During the last decade, aryl(hydro)boranes have established themselves as versatile novel building blocks for sophisticated boron-doped materials. This perspective article comprehensively discusses key structural motifs and reactivity patterns of recently developed aryl(hydro)boranes and shows how these have been used for the synthesis of macromolecular organoboranes through hydroboration polymerisation, ring-opening polymerisation and condensation polymerisation protocols. PMID:22546926

  16. Mild hypervalent iodine mediated oxidative nitration of N-aryl sulfonamides.

    Science.gov (United States)

    Kloeckner, Ulrich; Nachtsheim, Boris J

    2014-09-18

    An oxidative and acid-free method for the nitration of N-aryl sulfonamides has been developed using a combination of sodium nitrite as cheap and easy to handle NO2-source and the hypervalent iodine reagent PIFA as stoichiometric oxidant. Under very mild reaction conditions, the desired mononitrated aryl sulfonamides were isolated in up to 87% yield. This is the first example of an iodane-mediated oxidative nitration. PMID:25068377

  17. Palladium dichloride adduct of N,N-bis-(diphenylphosphanylmethyl)-2-aminopyridine: synthesis, structure and catalytic performance in the decarboxylative cross-coupling of 4-picolinic acid with aryl bromide.

    Science.gov (United States)

    He, Run-Tian; Wang, Jian-Feng; Wang, Hui-Fang; Ren, Zhi-Gang; Lang, Jian-Ping

    2014-07-01

    Reaction of PdCl2 with N,N-bis-(diphenylphosphanylmethyl)-2-aminopyridine (bdppmapy) afforded a mononuclear complex [(bdppmapy)PdCl2] (). Compound was characterized by elemental analysis, IR, (1)H, (13)C and (31)P NMR, electrospray ion mass spectra (ESI-MS) and X-ray single crystal crystallography. The Pd(ii) center in is chelated by bdppmapy, showing a cis-square planar geometry. With the assistance of additive Cu2O, complex exhibited good catalytic activity toward the decarboxylative cross-coupling reactions between 4-picolinic acid and aryl bromides. In the presence of only 2 mol% catalyst, a family of 4-aryl-pyridines could be isolated in up to 83% yield. PMID:24848973

  18. Synthesis and preliminary evaluation of selected 2-aryl-5(6)-nitro- 1H-benzimidazole derivatives as potential anticancer agents.

    Science.gov (United States)

    Romero-Castro, Aurelio; León-Rivera, Ismael; Avila-Rojas, Laura Citlalli; Navarrete-Vázquez, Gabriel; Nieto-Rodríguez, Alejandro

    2011-02-01

    In this study we report the synthesis and preliminary evaluation of a series of six 2-aryl-5(6)-nitro-1H-benzimidazole derivatives (1-6) as potential anticancer agents. Cytotoxicity was evaluated against seven human neoplastic cell lines using the MTT assay. Compound 6 [2-(4-chloro-3-nitrophenyl)-5(6)-nitro-1H-benzimidazole] was the most active of the series, showing an IC(50) of 28 nM against the A549 cell line. This compound displayed a selective in vitro cytotoxic activity index (>700) in non neoplastic HACAT cells (IC(50) = 22.2 ?M). Compounds 3 and 6 induce arrest in the S phase of the cell cycle, and compounds 1-6 induce apoptosis in the K562 cell line. Compound 6 induces poly (ADP-ribose) polymerase (PARP) inhibition activity as a potential mechanism of action. These results suggest that compound 6 could be a potent anticancer agent. Compound 3 displayed the best inhibitory activity against PARP with an IC(50) value of 0.05 ?M, compared to the activity shown by the positive control 3-aminobenzamide (IC(50) = 28.5 ?M). PMID:21380799

  19. 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

    Directory of Open Access Journals (Sweden)

    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.

  20. Synthesis and NMR Studies of (E)-1-Aryl-3-(2-pyrrolyl)-2-propenones and (E)-3-Aryl-1-(2-pyrrolyl)-2-propenones

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Synthesis and NMR Studies of (E)-1-Aryl-3-(2-pyrrolyl)-2-propenones and (E)-3-Aryl-1-(2-pyrrolyl)-2-propenones

    International Nuclear Information System (INIS)

    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 1H and 13C 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

  2. Identification of kaempferol as an inhibitor of cigarette smoke-induced activation of the aryl hydrocarbon receptor and cell transformation.

    Science.gov (United States)

    Puppala, D; Gairola, C G; Swanson, H I

    2007-03-01

    The aryl hydrocarbon receptor (AHR) is a cytosolic receptor which upon activation by its agonists, translocates into the nucleus and forms a dimer with ARNT (aryl hydrocarbon nuclear translocator). The AHR/ARNT dimer regulates the expression of its target genes by binding to DNA recognition elements termed dioxin responsive elements (DREs). Many AHR agonists, like the polyaromatic hydrocarbons and polyhalogenated hydrocarbons are known human carcinogens. Human exposure to these compounds is common due to their presence in air pollution and cigarette smoke. Interestingly, many dietary constituents that have chemo preventative properties have been found to also act as antagonists of the AHR pathway. Thus, a chemopreventive approach that may be effective in decreasing the incidences of many human cancers may involve a dietary regimen that includes a number of these naturally occurring AHR antagonists. With this idea in mind, we have assayed the ability of 15 flavonoids to inhibit AHR activated reporter activity and selected kaempferol for further analysis. Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1. Using an in vitro paradigm of events that are thought to occur during cigarette-smoke-induced lung cancer, we found that kaempferol also inhibited the ability of cigarette smoke condensate to induce growth of immortalized lung epithelial (BEAS-2B) cells in soft agar. Taken together, these results illustrate the promise associated with the use of flavonoids, that inhibit both AHR signaling and the carcinogenic actions of AHR agonists, for chemopreventive purposes. PMID:17012224

  3. Orthogonal Cu- and Pd-Based Catalyst Systems for the O- and N-Arylation of Aminophenols

    OpenAIRE

    Maiti, Debabrata; Buchwald, Stephen L.

    2009-01-01

    O- or N-arylated aminophenol products constitute a common structural motif in various potentially useful therapeutic agents and/or drug candidates. We have developed a complementary set of Cu- and Pd-based catalyst systems for the selective O- and N-arylation of unprotected aminophenols using aryl halides. Selective O-arylation of 3- and 4-aminophenols is achieved with copper-catalyzed methods employing picolinic acid or CyDMEDA, trans-N,N?-dimethyl-1,2-cyclohexanediamine, respectively, as ...

  4. Synthesis of 2-aryl-3-(2-cyanoethyl)aziridines and their chemical and enzymatic hydrolysis towards ?-lactams and ?-lactones.

    Science.gov (United States)

    Mollet, Karen; Decuyper, Lena; Vander Meeren, Saskia; Piens, Nicola; De Winter, Karel; Desmet, Tom; D'hooghe, Matthias

    2015-02-18

    Trans- and cis-2-aryl-3-(2-cyanoethyl)aziridines, prepared via alkylation of the corresponding 2-aryl-3-(tosyloxymethyl)aziridines with the sodium salt of trimethylsilylacetonitrile, were transformed into variable mixtures of 4-[aryl(alkylamino)methyl]butyrolactones and 5-[aryl(hydroxy)methyl]pyrrolidin-2-ones via KOH-mediated hydrolysis of the cyano group, followed by ring expansion. In addition, next to this chemical approach, enzymatic hydrolysis of the former aziridinyl nitriles by means of a nitrilase was performed as well, interestingly providing a selective route towards the above-mentioned functionalized ?-lactams. PMID:25598487

  5. Preparation and assessment of [99mTc]technetium aquacarbonyl complexes with 1,2-diaminoethane-N-substituted ligands for tumor detection

    International Nuclear Information System (INIS)

    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)

  6. In vitro cytotoxicity and apoptotic inducing activity of the synthesized 4-aryl-4H-chromenes derivatives against human cancer cell lines

    Directory of Open Access Journals (Sweden)

    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.

  7. Toxicological implications of polymorphisms in receptors for xenobiotic chemicals: The case of the aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    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 ity. 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

  8. Harman induces CYP1A1 enzyme through an aryl hydrocarbon receptor mechanism

    International Nuclear Information System (INIS)

    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 did 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.

  9. Induction of aryl hydrocarbon hydroxylase in rat tissue following intratracheal instillation of diesel particulate extract and benzo[a]pyrene.

    Science.gov (United States)

    Chen, K C

    1986-08-01

    The potential for aryl hydrocarbon hydroxylate (AHH) induction by inhaled diesel particles was assessed by intratracheal administration. Benzo[a]pyrene, (B[a]P) a reference compound, or an extract of particles, dissolved in gelatin-saline solution was administered to Fischer 344 rats at several dose levels. Twenty-four hours after administration of B[a]P or diesel particulate extract, the AHH activity increased in a dose-response manner in the lung, but not in liver. The maximum increase in the AHH activity in the lung was observed 12 h after intratracheal instillation of B[a]P (5 mg/kg), and the levels remained elevated for seven days. The AHH activity in the liver reached the maximum 24 h after the administration, and returned rapidly to control values. In contrast, intratracheal instillation of diesel particulate extract resulted in a significant increase of AHH activity in the lungs only after doses greater than 6 mg kg-1. The activity, however, declined rapidly and returned to control values within 75 h. The liver AHH activity in this instance, remained unchanged throughout the experimental period. These data indicate that in the lung, hydrocarbons extracted from diesel particles are weak enzyme inducers and exposure to these compounds by intratracheal administration did not result in AHH induction in the liver. The results suggest that doses higher than those normally expected from occupational exposures will be required to induce AHH activity in organs examined. PMID:2428858

  10. Aryl sulfate formation in sea urchins (Strongylocentrotus droebachiensis) ingesting marine algae (Fucus distichus) containing 2,6-dimethylnapthalene

    International Nuclear Information System (INIS)

    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 oxidationsng oxidations

  11. Nature of phenolic compounds in coffee melanoidins.

    Science.gov (United States)

    Coelho, Carina; Ribeiro, Miguel; Cruz, Ana C S; Domingues, M Rosário 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

  12. Efficient synthesis of antifungal active 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines in ionic liquids.

    Science.gov (United States)

    Gupta, Monika

    2011-08-15

    The title compounds, 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines 8, are synthesized from 5-aryl-3,4-diamino-1,2,4-triazoles 5 and 2-chloro-3-formylquinolines 7 in ionic liquid as solvent under microwave heating as well as using oil-bath heating at 80°C. The products are obtained in the good to moderate yields and in high purity. These compounds have been screened for antifungal activity. The screening data indicate that the compounds 8a, 8b, 8c and 8d show excellent activity against Aspergillus niger 1000 ?g concentration and Pencillium notatum species at 500 ?g as well as 1000 ?g concentrations whereas, these compounds show good to moderate activity against Aspergillus flavus and Rhizopus species at both the concentrations. Moreover, ionic liquid is found to be recyclable for at least three consecutive runs what makes the process cost-effective and economic that lead to the area of Green Chemistry as recyclability is one of the most important feature of Green Chemistry. PMID:21763133

  13. Estradiol regulates aryl hydrocarbon receptor expression in the rat uterus.

    Science.gov (United States)

    Kretzschmar, Georg; Papke, Anja; Zierau, Oliver; Möller, Frank Josef; Medjakovic, Svjetlana; Jungbauer, Alois; Vollmer, Günter

    2010-06-10

    Several authors have investigated the role of aryl hydrocarbon receptor (AHR) in the reproductive tract, but there are no data available whether 17beta-estradiol (E2) regulates expression of members of the AHR pathway in the uterus. We therefore examined the mRNA expression of Ahr as well as the genes of the AHR dimerization partners ARNT1 and ARNT2 and the AHR regulated genes Cyp1a1 and Gsta2 in the uterus of ovariectomized rats after administration of E2 at two different doses. The data show that Ahr mRNA expression is downregulated while AHR protein amounts increased in all uterine tissue compartments. In addition we observed a downregulation of Arnt1, Arnt2 and Cyp1a1 while Gsta2 mRNA expression is upregulated by E2 in a dose-dependent manner. These results show that members of the AHR pathway are regulated by E2 in the uterus. AHR may therefore play an important role in the mediation of uterine estrogenic effects. PMID:20176079

  14. Evodiamine as a novel antagonist of aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Research highlights: ? Evodiamine interacted with the AhR. ? Evodiamine inhibited the specific binding of [3H]-TCDD to the AhR. ? 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 Ki 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.

  15. 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

    International Nuclear Information System (INIS)

    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

  16. 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}

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. The evolution of aryl hydrocarbon signaling proteins: diversity of ARNT isoforms among fish species.

    Science.gov (United States)

    Powell, W H; Hahn, M E

    2000-01-01

    The aryl hydrocarbon receptor nuclear translocator (ARNT) mediates aryl hydrocarbon signaling and toxicity by dimerizing with the ligand-activated aryl hydrocarbon receptor (AHR), forming a complex that binds specific DNA elements and alters transcription of target genes. Two genes encode different forms of ARNT in rodents: ARNT1, which is widely expressed, and ARNT2, which exhibits a very restricted expression pattern. In an effort to characterize aryl hydrocarbon signaling mechanisms in fishes, we previously isolated an ARNT cDNA from Fundulus heteroclitus and discovered that this species expresses ARNT2 ubiquitously. This situation differs not only from mammals, but also from rainbow trout, which expresses a divergent ARNT gene that we hypothesized was peculiar to salmonids (rtARNTa/b). In this communication, we examine the ARNT sequences of multiple fish species, including a newly isolated cDNA from scup (Stenotomus chrysops). Our phylogenetic analysis demonstrates that zebrafish ARNT, like the Fundulus protein, is an ARNT2. Contrary to expectations, the scup ARNT is closely related to the rainbow trout protein, demonstrating that the existence of this ARNT isoform predates the divergence of salmonids from the other teleosts. Thus, different species of fish express distinct and highly conserved isoforms of ARNT. The number, type, and expression pattern of ARNT proteins may contribute to interspecies differences in aryl hydrocarbon toxicity, possibly through distinct interactions with additional PAS-family proteins. PMID:11460724

  18. Configuration-dependent electronic and magnetic properties of graphene monolayers and nanoribbons functionalized with aryl groups

    International Nuclear Information System (INIS)

    Graphene monolayers functionalized with aryl groups exhibit configuration-dependent electronic and magnetic properties. The aryl groups were adsorbed in pairs of neighboring atoms in the same sublattice A (different sublattices) of graphene monolayers, denoted as the M2AA (M2AB) configuration. The M2AA configuration behaved as a ferromagnetic semiconductor. The band gaps for the majority and minority bands were 1.1 eV and 1.2 eV, respectively. The M2AB configuration behaved as a nonmagnetic semiconductor with a band gap of 0.8 eV. Each aryl group could induce 1 Bohr magneton (?B) into the molecule-graphene system. Armchair graphene nanoribbons (GNRs) exhibited the same configuration-dependent magnetic properties as the graphene monolayers. The net spin of the functionalized zigzag GNRs was mainly localized on the edges demonstrating an adsorption site-dependent magnetism. For the zigzag GNRs, both the M2AA and M2AB configurations possibly had a magnetic moment. Each aryl group could induce 1.5–3.5 ?B into the molecule-graphene system. There was a metal-to-insulator transition after adsorption of the aryl groups for the zigzag GNRs

  19. Expedient synthesis of C-aryl carbohydrates by consecutive biocatalytic benzoin and aldol reactions.

    Science.gov (United States)

    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 ?-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

  20. Configuration-dependent electronic and magnetic properties of graphene monolayers and nanoribbons functionalized with aryl groups

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Xiaoqing, E-mail: xqtian2008@gmail.com; Gu, Juan [College of Physics and Technology, Shenzhen University, Shenzhen 518060, Guangdong (China); Xu, Jian-bin, E-mail: jbxu@ee.cuhk.edu.hk [Department of Electronic Engineering and Materials Science and Technology Research Center, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong)

    2014-01-28

    Graphene monolayers functionalized with aryl groups exhibit configuration-dependent electronic and magnetic properties. The aryl groups were adsorbed in pairs of neighboring atoms in the same sublattice A (different sublattices) of graphene monolayers, denoted as the M{sub 2}{sup AA} (M{sub 2}{sup AB}) configuration. The M{sub 2}{sup AA} configuration behaved as a ferromagnetic semiconductor. The band gaps for the majority and minority bands were 1.1 eV and 1.2 eV, respectively. The M{sub 2}{sup AB} configuration behaved as a nonmagnetic semiconductor with a band gap of 0.8 eV. Each aryl group could induce 1 Bohr magneton (?{sub B}) into the molecule-graphene system. Armchair graphene nanoribbons (GNRs) exhibited the same configuration-dependent magnetic properties as the graphene monolayers. The net spin of the functionalized zigzag GNRs was mainly localized on the edges demonstrating an adsorption site-dependent magnetism. For the zigzag GNRs, both the M{sub 2}{sup AA} and M{sub 2}{sup AB} configurations possibly had a magnetic moment. Each aryl group could induce 1.5–3.5 ?{sub B} into the molecule-graphene system. There was a metal-to-insulator transition after adsorption of the aryl groups for the zigzag GNRs.

  1. Palladium-Catalyzed Cs2CO3-Promoted Arylation of Unactivated C(sp(3))-H Bonds by (Diacetoxyiodo)arenes: Shifting the Reactivity of (Diacetoxyiodo)arenes from Acetoxylation to Arylation.

    Science.gov (United States)

    Gou, Quan; Zhang, Zhao-Fu; Liu, Zhi-Cheng; Qin, Jun

    2015-03-20

    PdCl2(CH3CN)2-catalyzed arylation of unactivated C(sp(3))-H bonds using (diacetoxyiodo)arenes as arylation reagents is reported. The reactivity of (diacetoxyiodo)arenes as arylation reagents is enabled in the presence of Cs2CO3 under the reaction conditions. This arylation method is highly efficient and occurs without the use of silver salt. The reaction tolerates a broad substrate scope that was not demonstrated by other silver salt-free C(sp(3))-H bond arylation conditions. The synthetic utility of the method is further illustrated in the synthesis of the psychotropic drug phenibut. A detailed mechanism study has been conducted to understand the reaction pathway. PMID:25763683

  2. Copper-Catalyzed N-Arylation of Amides Using (S-N-Methylpyrrolidine-2-carboxylate as the Ligand

    Directory of Open Access Journals (Sweden)

    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.

  3. Fluorogenic derivatization of aryl halides based on the formation of biphenyl by Suzuki coupling reaction with phenylboronic acid.

    Science.gov (United States)

    Kishikawa, Naoya; Kubo, Kimiko; Hammad, Sherin Farouk; Mabrouk, Mokhtar Mohamed; Habib, Ahmed; Elfatatry, Hamed; Ohyama, Kaname; Nakashima, Kenichiro; Kuroda, Naotaka

    2009-10-01

    The fluorogenic derivatization method for aryl halide was developed for the first time. This method was based on the formation of fluorescent biphenyl structure by Suzuki coupling reaction between aryl halides and non-fluorescent phenylboronic acid (PBA). We measured the fluorescence spectra of the products obtained by the reaction of p-substituted aryl bromides (i.e., 4-bromobenzonitrile, 4-bromoanisole, 4-bromobenzoic acid ethyl ester and 4-bromotoluene) with PBA in the presence of palladium (II) acetate as a catalyst. The significant fluorescence at excitation maximum wavelength of 275-290 nm and emission maximum wavelength of 315-350 nm was detected in all the tested aryl bromides. This result demonstrated that non-fluorescent aryl bromides could be converted to the fluorescent biphenyl derivatives by the coupling reaction with non-fluorescent PBA. We tried to determine these aryl bromides by HPLC-fluorescence detection with pre-column derivatization. The aryl bromide derivatives were detected on the chromatogram within 30 min without any interfering peak derived from the reagent blank. The detection limits (S/N=3) for aryl bromides were 13-157 fmol/injection. PMID:19717162

  4. Nickel-catalyzed reductive and borylative cleavage of aromatic carbon-nitrogen bonds in N-aryl amides and carbamates.

    Science.gov (United States)

    Tobisu, Mamoru; Nakamura, Keisuke; Chatani, Naoto

    2014-04-16

    The nickel-catalyzed reaction of N-aryl amides with hydroborane or diboron reagents resulted in the formation of the corresponding reduction or borylation products, respectively. Mechanistic studies revealed that these reactions proceeded via the activation of the C(aryl)-N bonds of simple, electronically neutral substrates and did not require the presence of an ortho directing group. PMID:24684671

  5. Synthesis of 3-aryl-1-[(4-phenyl-1-piperazinyl)butyl]indazole derivatives and their affinity to 5-HT1A serotonin and dopamine D1 receptors.

    Science.gov (United States)

    Andronati, S; Sava, V; Makan, S; Kolodeev, G

    1999-02-01

    Eight 3-arylindazole derivatives have been synthesized and their affinity to 5-HT1A serotonin and D1 dopamine receptors was investigated by radioligand analysis. Quantitative structure-activity relationships were studied using the Free-Wilson model. An increase in affinity to dopamine D1 receptors within substituents Br > Cl > CH3 at the 5-position of the 3-arylindazole molecule has been observed. Addition of a chlorine atom to the ortho-position the of phenyl ring let to even highest activity. Replacement of the hydrogen atom at the first position of the 3-arylindazole on the (phenylpiperazine)butyl substituent caused an increase of affinity and did not change the trends of affinity dependence on structure. An inverse dependence on the structure of the studied compounds was observed for the serotonin 5-HT1A receptors. Compounds containing a methyl group at the 5-position of molecule were more active than compounds containing halogens. A chlorine atom at the ortho-position of the phenyl ring decreased affinity. Replacement of the hydrogen atom at the first position of the molecule on the phenylpiperazine)butyl substituent led to an increase in affinity. Selectivity of the studied compounds varied within a wide range. Generally, the presence of the 3-aryl-indazole fragment in the new buspirone analogues increased their affinity to dopamine receptors and reduced their affinity to serotonin receptors. Compounds containing a bromine atom in the 3-arylindazole moiety may be promising ligands for D1 receptors. PMID:10084155

  6. N?-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as receptor tyrosine kinase inhibitors.

    Science.gov (United States)

    Gangjee, Aleem; Kurup, Sonali; Ihnat, Michael A; Thorpe, Jessica E; Disch, Bryan

    2012-01-15

    Six novel N(4)-substitutedphenyl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines were synthesized as multiple receptor tyrosine kinase (RTK) inhibitors and antitumor agents. An improvement in the inhibitory potency against epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 1 (VEGFR-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) assays and in the A431 cellular proliferation assay was observed for compounds 8-13 over the previously reported 5-7. Three compounds (8, 9 and 13) demonstrated potent, multiple RTK inhibition and were more potent or equipotent compared to the lead compounds 5 and 7 and the standard compounds. Compounds 10 and 12 showed potent inhibition of VEGFR-2 over EGFR, platelet-derived growth factor receptor-? (PDGFR-?) and VEGFR-1. The results indicate that the RTK inhibitory profile could be modulated with slight variations to the N(4)-aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamino scaffold. PMID:22204741

  7. An exploration of Suzuki aryl cross coupling chemistry involving [2.2]paracyclophane derivatives.

    Science.gov (United States)

    Roche, Alex J; Canturk, Belgin

    2005-02-01

    Suzuki aryl cross coupling reactions using derivatives of [2.2]paracyclophane were examined. A variety of aryl boronic acids and pinacolate esters were successfully cross coupled with 4-bromo[2.2]paracyclophane under standard Suzuki conditions. Whilst an excellent tolerance for electron donating and withdrawing groups was observed, cross coupling reactions with highly sterically demanding borates (e.g. mesityl) were unsuccessful. The preparation and stability of the previously unreported [2.2]paracyclophanyl-4-boronic acid, -pinacolate ester and -dimethyl ester are described, along with the utility of these systems in Suzuki aryl cross coupling reactions. Application of this methodology led to a dicyclophane containing two [2.2]paracyclophane units separated by a 4-4' connected biphenyl spacer group. PMID:15678191

  8. Pd-catalyzed Heck reactions of aryl bromides with 1,2-diarylethenes

    Energy Technology Data Exchange (ETDEWEB)

    Limberger, Jones; Poersch, Silvia; Monteiro, Adriano L., E-mail: adriano.monteiro@ufrgs.b [Universidade Federal do Rio Grande do Sul (LCM/UFRGS), Porto Alegre, RS (Brazil). Lab. of Molecular Catalysis

    2011-07-01

    A catalytic system composed of Pd(OAc){sub 2} and P(o-tol){sub 3} was found to be effective for the Heck reaction of aryl bromides with diarylethylenes. Using K{sub 2}CO{sub 3} as a base and DMF as a solvent, trisubstituted olefins were obtained in good to excellent yields. Aryl bromides containing an electron-withdrawing group in para position were less reactive for the Heck coupling reaction and gave substantial amount of homocoupling by-product suggesting that oxidative addition is not the rate-determining step. Electron withdrawing group substituent in the para position of stilbene affects the regioselectivity of the reaction. In this case, the phenyl group from the Ph-Pd complex migrates preferentially to the same carbon of the double bond to which the phenyl is bonded. Finally, a one pot sequential double Heck arylation of styrene was performed, giving trisubstituted olefin with an overall yield of 73%. (author)

  9. Dual catalysis. Merging photoredox with nickel catalysis: coupling of ?-carboxyl sp³-carbons with aryl halides.

    Science.gov (United States)

    Zuo, Zhiwei; Ahneman, Derek T; Chu, Lingling; Terrett, Jack A; Doyle, Abigail G; MacMillan, David W C

    2014-07-25

    Over the past 40 years, transition metal catalysis has enabled bond formation between aryl and olefinic (sp(2)) carbons in a selective and predictable manner with high functional group tolerance. Couplings involving alkyl (sp(3)) carbons have proven more challenging. Here, we demonstrate that the synergistic combination of photoredox catalysis and nickel catalysis provides an alternative cross-coupling paradigm, in which simple and readily available organic molecules can be systematically used as coupling partners. By using this photoredox-metal catalysis approach, we have achieved a direct decarboxylative sp(3)-sp(2) cross-coupling of amino acids, as well as ?-O- or phenyl-substituted carboxylic acids, with aryl halides. Moreover, this mode of catalysis can be applied to direct cross-coupling of C(sp³)-H in dimethylaniline with aryl halides via C-H functionalization. PMID:24903563

  10. Microwave assisted synthesis of 2-pyridone and 2-pyridone based compounds

    Directory of Open Access Journals (Sweden)

    Mijin Dušan Ž.

    2014-01-01

    Full Text Available 2-Pyridones are important heterocyclic compounds that are widely used in medical chemistry, and their various derivatives have significant biological and medical applications. In this paper, the synthesis of 2-pyridones as well as 2-pyridone based compounds such as 2-quinolones using microwave assisted organic chemistry is reviewed. The review is divided in three parts. In the first part, microwave synthesis of 2-pyridones according to the type of condensation is discussed. In the second part, microwave assisted synthesis of 2-quionolones is listed. At the end of the review several examples of microwave synthesis of other 2-pyridone based compounds (ring fused N-substituted 2-pyridones are given. [Projekat Ministarstva nauke Republike Srbije, br. 172013

  11. Polybenzimidazole compounds

    Energy Technology Data Exchange (ETDEWEB)

    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)

    2010-08-10

    A PBI compound that includes imidazole nitrogens, at least a portion of which are substituted with an organic-inorganic hybrid moiety. 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 PBI compound may exhibit similar thermal properties in comparison to the unsubstituted PBI. The PBI compound may exhibit a solubility in an organic solvent greater than the solubility of the unsubstituted PBI. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may occur at about room temperature and/or at about atmospheric pressure. Substituting may use at least five equivalents in relation to the imidazole nitrogens to be substituted or, preferably, about fifteen equivalents.

  12. Polybenzimidazole compounds

    Energy Technology Data Exchange (ETDEWEB)

    Klaehn, John R. (Idaho Falls, ID); Peterson, Eric S. (Idaho Falls, ID); Orme, Christopher J. (Shelley, ID); Jones, Michael G. (Chubbuck, ID); Wertsching, Alan K. (Idaho Falls, ID); Luther, Thomas A. (Idaho Falls, ID); Trowbridge, Tammy L. (Idaho Falls, ID)

    2011-11-22

    A PBI compound includes imidazole nitrogens at least a portion of which are substituted with a moiety containing a carbonyl group, the substituted imidazole nitrogens being bonded to carbon of the carbonyl group. At least 85% of the nitrogens may be substituted. The carbonyl-containing moiety may include RCO--, where R is alkoxy or haloalkyl. The PBI compound may exhibit a first temperature marking an onset of weight loss corresponding to reversion of the substituted PBI that is less than a second temperature marking an onset of decomposition of an otherwise identical PBI compound without the substituted moiety. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may use more than 5 equivalents in relation to the imidazole nitrogens to be substituted.

  13. ANTIMICROBIAL ACTIVITY OF DIFFERENT THIOSEMICARBAZONE COMPOUNDS AGAINST MICROBIAL PATHOGENS

    Directory of Open Access Journals (Sweden)

    Negi Parul

    2012-05-01

    Full Text Available Thiosemicarbazone belongs to a large group of thiourea derivatives, whose biological activities are a function of parent aldehyde or ketone moiety. They have been evaluated over the last 50 year as antiviral, antibacterial, antifungal, antimalarial, anticancer, leprosy, rheumatism, trypanosomiasis and coccidiodis. Thiosemicarbazones were prepared by simple process in which N4-thiosemicarbazone moiety was replaced by aliphatic, arylic and cyclic amines. Present study reported the anti-microbial activity of different thiosemicarbazone compounds against certain bacterial and fungal pathogens viz. Bacillus cereus, Staphylococcus epidermis, Moraxella cattarhalis, Staph. Saprophyticus, Candida albicans and Aspergillus flavans.

  14. Ultraviolet photoinduced weak bonds in aryl-substituted polysilanes

    Energy Technology Data Exchange (ETDEWEB)

    Schauer, F [Polymer Centre, Tomas Bata University in Zlin, Faculty of Technology, T G Masaryka 275, CZ 762 72 Zlin (Czech Republic); Kuritka, I [Polymer Centre, Tomas Bata University in Zlin, Faculty of Technology, T G Masaryka 275, CZ 762 72 Zlin (Czech Republic); Saha, P [Polymer Centre, Tomas Bata University in Zlin, Faculty of Technology, T G Masaryka 275, CZ 762 72 Zlin (Czech Republic); Nespurek, S [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague (Czech Republic)

    2007-02-21

    The susceptibility of aryl-substituted polysilylenes to photodegradation by ultraviolet (UV) radiation is examined on the prototypical materials poly[methyl(phenyl)silylene] (PMPSi) and poly[(biphenyl-4-yl)methylsilylene] (PBMSi). We extend the scope of our last paper (Schauer et al 2004 Polym. Degrad. Stabil. 84 383) with the elucidation of the degradation mechanisms for two different degradation wavelengths: 266 and 355 nm. The main purpose of this paper was to study photoluminescence (PL) after major degradation, predominantly in long-wavelength range 400-600 nm, studying the disorder, dangling bonds (DBs) and weak bonds (WBs) created by the degradation process. We claim that the PL of the 500-600 nm band is related to the existence of WBs on the Si chain and originates in the {sigma}*-{sigma} exciton migration at room temperature by diffusion, free electron-hole formation, trapping in WBs and subsequent radiative recombination by tunnelling. Increase of the normalized PL 520-540 nm band after UV degradation can be then evaluated as the increase of the density of states (DOS) of WBs. The efficiency of the WB creation in PMPSi is greater for 266 nm irradiation, supporting the notion of the suppressed exciton transport compared to the less energetical photon of 355 nm, where the WB creation is lowered due to the exciton migration to longer segments and/or already existing defects. For PBMSi the WB creation kinetics for 355 nm degradation is similar to that of PMPSi. The 266 nm degradation results then support the model calculations of DB and WB reconstruction in the more rigid Si skeleton.

  15. Ultraviolet photoinduced weak bonds in aryl-substituted polysilanes

    International Nuclear Information System (INIS)

    The susceptibility of aryl-substituted polysilylenes to photodegradation by ultraviolet (UV) radiation is examined on the prototypical materials poly[methyl(phenyl)silylene] (PMPSi) and poly[(biphenyl-4-yl)methylsilylene] (PBMSi). We extend the scope of our last paper (Schauer et al 2004 Polym. Degrad. Stabil. 84 383) with the elucidation of the degradation mechanisms for two different degradation wavelengths: 266 and 355 nm. The main purpose of this paper was to study photoluminescence (PL) after major degradation, predominantly in long-wavelength range 400-600 nm, studying the disorder, dangling bonds (DBs) and weak bonds (WBs) created by the degradation process. We claim that the PL of the 500-600 nm band is related to the existence of WBs on the Si chain and originates in the ?*-? exciton migration at room temperature by diffusion, free electron-hole formation, trapping in WBs and subsequent radiative recombination by tunnelling. Increase of the normalized PL 520-540 nm band after UV degradation can be then evaluated as the increase of the density of states (DOS) of WBs. The efficiency of the WB creation in PMPSi is greater for 266 nm irradiation, supporting the notion of the suppressed exciton transport compared to the less energetical photon of 355 nm, where the WB creation is lowered due to the exciton migration to longer segments and/or already existing defects. For PBMSi the WB creation kinetics for 355 nm degradation is similar to that of PMPSi. The 266 nm is similar to that of PMPSi. The 266 nm degradation results then support the model calculations of DB and WB reconstruction in the more rigid Si skeleton

  16. Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

    Directory of Open Access Journals (Sweden)

    Elizabeth P. Jones

    2011-11-01

    Full Text Available A method was developed for the synthesis of ?-alkyl, ?-aryl-bislactim ethers in good to excellent yields and high diastereoselectivities, consisting of a facile one-pot procedure in which the aryl group is introduced by means of a nucleophilic addition to benzyne and the alkyl group by alkylation of a resultant benzylic anion. Hydrolysis of the sterically less hindered adducts gave the corresponding quaternary amino acids with no racemization, whereas hydrolytic ring opening gave the corresponding valine dipeptides from bulkier bislactims.

  17. Ralfuranone Is Produced by an Alternative Aryl-Substituted ?-Lactone Biosynthetic Route in Ralstonia solanacearum.

    Science.gov (United States)

    Pauly, Julia; Nett, Markus; Hoffmeister, Dirk

    2014-07-17

    The aryl-substituted ?-lactones ralfuranones A and B were isolated after feeding l-[1-(13)C]-phenylalanine to a liquid culture of the plant pathogenic bacterium Ralstonia solanacearum. (13)C NMR analysis demonstrated specific enrichment of the label at position 2 of the ?-lactone. This labeling pattern is consistent with a biosynthetic mechanism that includes direct cyclization of two monomeric phenylpyruvate precursors into an ?,?-substituted lactone, but incompatible with a terphenylquinone intermediate. As the latter was shown as an intermediate in allantofuranone biosynthesis, we conclude that aryl-substituted ?-lactones can be assembled via divergent biosynthetic routes. PMID:25033087

  18. Kinetic and chemical characterization of aldehyde oxidation by fungal aryl-alcohol oxidase

    OpenAIRE

    Ferreira, Patricia; Herna?ndez-ortega, Aitor; Herguedas, Beatriz; Rencoret, Jorge; Gutie?rrez, Ana; Marti?nez, Maria Jesu?s; Jime?nez-barbero, Jesu?s; Medina, Milagros; Marti?nez, A?ngel 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...

  19. Comparative measure of the electronic influence of highly substituted aryl isocyanides.

    Science.gov (United States)

    Carpenter, Alex E; Mokhtarzadeh, Charles C; Ripatti, Donald S; Havrylyuk, Irena; Kamezawa, Ryo; Moore, Curtis E; Rheingold, Arnold L; Figueroa, Joshua S

    2015-03-16

    To assess the relative electronic influence of highly substituted aryl isocyanides on transition metal centers, a series of C4v-symmetric Cr(CNR)(CO)5 complexes featuring various alkyl, aryl, and m-terphenyl substituents have been prepared. A correlation between carbonyl-ligand (13)C{(1)H} NMR chemical shift (?CO) and calculated Cotton-Kraihanzel (C-K) force constant (kCO) is presented for these complexes to determine the relative changes in isocyanide ?-donor/?-acid ratio as a function of substituent identity and pattern. For nonfluorinated aryl isocyanides possessing alkyl or aryl substitution, minimal variation in effective ?-donor/?-acid ratio is observed over the series. In addition, aryl isocyanides featuring strongly electron-releasing substituents display an electronic influence that nearly matches that of nonfluorinated alkyl isocyanides. Lower ?-donor/?-acid ratios are displayed by polyfluorinated aryl isocyanide ligands. However, the degree of this attenuation relative to nonfluorinated aryl isocyanides is not substantial and significantly higher ?-donor/?-acid ratios than CO are observed in all cases. Substituent patterns for polyfluorinated aryl isocyanides are identified that give rise to low relative ?-donor/?-acid ratios but offer synthetic convenience for coordination chemistry applications. In order to expand the range of available substitution patterns for comparison, the syntheses of the new m-terphenyl isocyanides CNAr(Tripp2), CNp-MeAr(Mes2), CNp-MeAr(DArF2), and CNp-FAr(DArF2) are also reported (Ar(Tripp2) = 2,6-(2,4,6-(i-Pr)3C6H2)2C6H3); p-MeAr(Mes2) = 2,6-(2,4,6-Me3C6H2)2-4-Me-C6H2); p-MeAr(DArF2) = 2,6-(3,5-(CF3)2C6H3)2-4-Me-C6H2); p-FAr(DArF2) = 2,6-(3,5-(CF3)2C6H3)2-4-F-C6H2). PMID:25700244

  20. Studying regioisomer formation in the Pd-catalyzed fluorination of aryl triflates by deuterium labeling.

    Science.gov (United States)

    Milner, Phillip J; Kinzel, Tom; Zhang, Yong; Buchwald, Stephen L

    2014-11-01

    Isotopic labeling has been used to determine that a portion of the desired product in the Pd-catalyzed fluorination of electron-rich, non-ortho-substituted aryl triflates results from direct C-F cross-coupling. In some cases, formation of a Pd-aryne intermediate is responsible for producing undesired regioisomers. The generation of the Pd-aryne intermediate occurs primarily via ortho-deprotonation of a L·Pd(Ar)OTf (L = biaryl monophosphine) species by CsF and thus competes directly with the transmetalation step of the catalytic cycle. Deuterium labeling studies were conducted with a variety of aryl triflates. PMID:25299957

  1. Stabilized well-dispersed Pd(0) nanoparticles for aminocarbonylation of aryl halides.

    Science.gov (United States)

    Zhu, Yinghuai; Chuanzhao, Li; Biying, Algin Oh; Sudarmadji, Meriska; Chen, Anqi; Tuan, Dang Thanh; Seayad, Abdul M

    2011-09-28

    Well-dispersed palladium (0) nanoparticles stabilized with phosphonium based ionic liquid were synthesized conveniently and fully characterized. A catalyst system comprising of the Pd(0) nanoparticles and a base was found to be recyclable and efficient for the aminocarbonylation reaction of aryl iodide in ionic liquid media. In the presence of potassium tert-butyloxide, for the relatively stable aryl chloride and bromide substrates, medium activities were achieved for the catalyst. The catalyst composites can be recycled at least five times with sustained activity. PMID:21842062

  2. The application of (Z)-3-aryl-3-haloenoic acids to the synthesis of (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones

    OpenAIRE

    Gupton, John T.; Telang, Nakul; Banner, Edith J.; Kluball, Emily J.; Hall, Kayleigh E.; Finzel, Kara L.; Jia, Xin; Bates, Spencer R.; Welden, R. Scott; Giglio, Benjamin C.; Eaton, James E.; Barelli, Peter J.; Firich, Lauren T.; Stafford, John A.; Coppock, Matthew B.

    2010-01-01

    Studies directed at the synthesis of (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones from (Z)-3-aryl-3-haloenoic acids are described. The successful strategy relies on the preparation of (Z)-3-aryl-3-haloenoic acids from acetophenones through the corresponding (Z)-3-aryl-3-haloenals and the conversion of the (Z)-3-aryl-3-haloenoic acids to (Z)-5-benzylidene-4-aryl-5H-furan-2-ones. The furanones were subsequently treated with primary amines and dehydrated to the corresponding (Z)-5-benzylidene-4-ary...

  3. Synthesis of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazines that have antibacterial activity and also inhibit inorganic pyrophosphatase.

    Science.gov (United States)

    Lv, Wei; Banerjee, Biplab; Molland, Katrina L; Seleem, Mohamed N; Ghafoor, Adil; Hamed, Maha I; Wan, Baojie; Franzblau, Scott G; Mesecar, Andrew D; Cushman, Mark

    2014-01-01

    Inorganic pyrophosphatases are potential targets for the development of novel antibacterial agents. A pyrophosphatase-coupled high-throughput screening assay intended to detect o-succinyl benzoic acid coenzyme A (OSB CoA) synthetase inhibitors led to the unexpected discovery of a new series of novel inorganic pyrophosphatase inhibitors. Lead optimization studies resulted in a series of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazine derivatives that were prepared by an efficient synthetic pathway. One of the tetracyclic triazine analogues 22h displayed promising antibiotic activity against a wide variety of drug-resistant Staphylococcus aureus strains, as well as activity versus Mycobacterium tuberculosis and Bacillus anthracis, at a concentration that was not cytotoxic to mammalian cells. PMID:24315189

  4. Eaton's reagent-mediated domino ?-cationic arylations of aromatic carboxylic acids to Iasi-red polymethoxylated polycyclic aromatic hydrocarbons: products with unprecedented biological activities as tubulin polymerization inhibitors.

    Science.gov (United States)

    Ghinet, Alina; Gautret, Philippe; Hijfte, Nathalie Van; Ledé, Bertrand; Hénichart, Jean-Pierre; Bîcu, Elena; Darbost, Ulrich; Rigo, Benoît; Daïch, Adam

    2014-08-01

    A rapid domino ?-cationic arylation of aromatic carboxylic acids, mediated by Eaton's reagent, has been developed for the synthesis of Iasi-red polymethoxylated polycyclic aromatic hydrocarbons (PAHs). This route is currently the easiest method to obtain such popular PAH compounds, which bear in addition numerous methoxy groups. The domino process was generalized, the structure of the obtained red products and the mechanism of their formations were elucidated, and some of their photophysical properties were determined. Newly synthesized polymethoxylated-PAHs were tested for their interaction with tubulin polymerization as well as for their cytotoxicity on a panel of NCI-60 human cancer cell lines. Interestingly, one of these rubicene derivatives exhibited remarkable cytotoxicity in vitro, including inhibition of leukemia, colon, melanoma, CNS, and ovarian cancer cell lines with GI50 values in the low nanomolar range (GI50 < 10?nM). PMID:25042333

  5. Muscarinic receptor 1 agonist activity of novel N-aryl carboxamide substituted 3-morpholino arecoline derivatives in Alzheimer's presenile dementia models.

    Science.gov (United States)

    Malviya, Manish; Kumar, Y C Sunil; Mythri, R B; Venkateshappa, C; Subhash, M N; Rangappa, K S

    2009-08-01

    Earlier we have reported the effect of arecoline thiazolidinone and morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer's presenile dementia models. To elucidate further our Structure-Activity Relationship (SAR) studies on the chemistry and muscarinic receptor 1 binding efficacy, a series of novel carboxamide derivatives of 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine molecule have been designed and synthesized as a new class of M1 receptor agonists with a low toxicity effect profile that enhances memory function in animal models of Alzheimer's presenile dementia and also modulates the APP secretion from rat brain cerebrocortical slices by activating M1 receptor in vitro. Results suggest that compound 9b having methyl group at the para position of the aryl group attached to the carboxamide of morpholino arecoline could emerge as a potent molecule having antidementia activity. PMID:19595599

  6. Pharmacokinetic optimization of 4-substituted methoxybenzoyl-aryl-thiazole and 2-aryl-4-benzoyl-imidazole for improving oral bioavailability.

    Science.gov (United States)

    Li, Chien-Ming; Chen, Jianjun; Lu, Yan; Narayanan, Ramesh; Parke, Deanna N; Li, Wei; Ahn, Sunjoo; Miller, Duane D; Dalton, James T

    2011-10-01

    Microtubules are critical components of the cytoskeleton. Perturbing their function arrests the growth of a broad spectrum of cancer cell lines, making microtubules an excellent and established target for chemotherapy. All of the U.S. Food and Drug Administration-approved antitubulin agents bind to paclitaxel or vinblastine binding sites in tubulin. Because of the complexity of their structures, it is difficult to structurally modify the vinca alkaloids and taxanes and develop orally bioavailable agents. Antitubulin agents that target the colchicine-binding site in tubulin may provide a better opportunity to be developed for oral use because of their relatively simple structures and physicochemical properties. A potent antitubulin agent, 4-(3,4,5-trimethoxybenzoyl)-2-phenyl-thiazole (SMART-H), binding to the colchicine-binding site, was discovered in our laboratory. However, the bioavailability of SMART-H was low because of its poor solubility. Structural modification of SMART-H led to the development of 2-aryl-4-benzoyl-imidazole analog (ABI-274), with improved bioavailability and potency but still considerable first-pass metabolism. A chlorine derivative (ABI-286), replacing the methyl site of ABI-274, resulted in 1.5-fold higher metabolic stability in vitro and 1.8-fold lower clearance in rats in vivo, indicating that metabolic stability of ABI-274 can be extended by blocking benzylic hydroxylation. Overall, ABI-274 and ABI-286 provided 2.4- and 5.5-fold increases in exposure (area under the curve) after oral dosing in rats compared with SMART-H. Most importantly, the structural modifications did not compromise potency. ABI-286 exhibited moderate clearance, moderate volume of distribution, and acceptable oral bioavailability. This study provided the first evidence that ABI-286 may be the first member of a new class of orally bioavailable antitubulin agents. PMID:21742898

  7. Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

    DEFF Research Database (Denmark)

    McNamara, Yvonne M.; Cloonan, Suzanne M.

    2011-01-01

    Structural derivatives of 4-MTA, an illegal amphetamine analogue have been previously shown to have anticancer effects in vitro. In this study we report the synthesis of a series of novel 1,3-bis(aryl)-2-nitro-1-propene derivatives related in structure to 4-MTA. A number of these compounds containing a classic nitrostyrene structure are shown to have antiproliferative activities in vitro in a range of malignant cell lines, particularly against Burkitt’s lymphoma derived cell lines, whilst having no effect on ‘normal’ peripheral blood mononuclear cells. Such effects appear to be independent of the serotonin transporter, a high affinity target for amphetamines and independent of protein tyrosine phosphatases and tubulin dynamics both of which have been previously associated with nitrostyrene-induced cell death. We demonstrate that a number of these compounds induce caspase activation, PARP cleavage, chromatin condensation and membrane blebbing in a Burkitt’s lymphoma derived cell line, consistent with these compounds inducing apoptosis in vitro. Although no specific target has yet been identified for the action of these compounds, the cell death elicited is potent, selective and worthy of further investigation.

  8. Design, microwave-mediated synthesis and biological evaluation of novel 4-aryl(alkyl)amino-3-nitroquinoline and 2,4-diaryl(dialkyl)amino-3-nitroquinolines as anticancer agents.

    Science.gov (United States)

    Chauhan, Monika; Rana, Anil; Alex, Jimi Marin; Negi, Arvind; Singh, Sandeep; Kumar, Raj

    2015-02-01

    Design, microwave-assisted synthesis of novel 4-aryl (alkyl)amino-3-nitroquinoline (1a-1l) and 2,4-diaryl (dialkyl)amino-3-nitroquinolines (2a-2k and 3a) via regioselective and complete nucleophilic substitution of 2,4-dichloro-3-nitroquinoline, respectively in water are presented. The newly synthesized compounds were evaluated for the first time for antiproliferative activity against EGFR overexpressing human lung (A-549 and H-460) and colon (HCT-116-wild type and HCT-116-p53 null) cancer cell lines. Some notions about structure-activity relationships (SAR) are presented. Compounds 2e, 2f, 2j and 3a overall exhibited excellent anticancer activity comparable to erlotinib which was used as a positive control. Molecular modeling studies disclosed the recognition pattern of the compounds and also supported the observed SAR. PMID:25462621

  9. Polymer compound

    OpenAIRE

    Lange, Rfm; Meijer, Ew

    1995-01-01

    A Polymer compound comprising a polymer (a) that contains cyclic imidesgroups and a polymer (b) that contains monomer groups with a 2,4-diamino-1,3,5-triazine side group. According to the formula (see formula) whereby themole percentage ratio of the cyclic imides groups in the polymer compoundwith respect to the mole percentage of the monomer units with 2,4-diamino-1,3,5-triazine side group in the polymer compound is 0.1-10.0. Preferablypolymer (a) and/or polymer (b) contain styrene and/or al...

  10. Aryl Hydrocarbon Receptor Activation and Developmental Toxicity in Zebrafish in Response to Soil Extracts Containing Unsubstituted and Oxygenated PAHs.

    Science.gov (United States)

    Wincent, Emma; Jönsson, Maria E; Bottai, Matteo; Lundstedt, Staffan; Dreij, Kristian

    2015-03-17

    Many industrial sites are polluted by complex mixtures of polycyclic aromatic compounds (PACs). Besides polycyclic aromatic hydrocarbons (PAHs), these mixtures often contain significant amounts of more polar PACs including oxygenated PAHs (oxy-PAHs). The effects of oxy-PAHs are, however, poorly known. Here we used zebrafish embryos to examine toxicities and transcriptional changes induced by PAC containing soil extracts from three different industrial sites: a gasworks (GAS), a former wood preservation site (WOOD), and a coke oven (COKE), and to PAH and oxy-PAH containing fractions of these. All extracts induced aryl hydrocarbon receptor (Ahr)-regulated mRNAs, malformations, and mortality. The WOOD extract was most toxic and the GAS extract least toxic. The extracts induced glutathione transferases and heat shock protein 70, suggesting that the toxicity also involved oxidative stress. With all extracts, Ahr2-knock-down reduced the toxicity, indicating a significant Ahr2-dependence on the effects. Ahr2-knock-down was most effective with the PAH fraction of the WOOD extract and with the oxy-PAH fraction of the COKE extract. Our results indicate that oxy-PAH containing mixtures can be as potent Ahr activators and developmental toxicants as PAHs. In addition to Ahr activating potency, the profile of cytochrome P4501 inhibitors may also determine the toxic potency of the extracts. PMID:25715055

  11. Room Temperature Aryl Trifluoromethylation via Copper- Mediated Oxidative Cross-Coupling

    OpenAIRE

    Buchwald, Stephen Leffler; Senecal, Todd D.; Parsons, Andrew

    2010-01-01

    A method for the room temperature copper-mediated trifluoromethylation of aryl and heteroaryl boronic acids has been developed. This protocol is amenable to normal benchtop setup and reactions typically require only 1?4 h. Proceeding under mild conditions, the method tolerates a range of functional groups, allowing access to a variety of trifluoromethylarenes.

  12. Room temperature aryl trifluoromethylation via copper-mediated oxidative cross-coupling.

    Science.gov (United States)

    Senecal, Todd D; Parsons, Andrew T; Buchwald, Stephen L

    2011-02-18

    A method for the room temperature copper-mediated trifluoromethylation of aryl and heteroaryl boronic acids has been developed. This protocol is amenable to normal benchtop setup and reactions typically require only 1-4 h. Proceeding under mild conditions, the method tolerates a range of functional groups, allowing access to a variety of trifluoromethylarenes. PMID:21235259

  13. A general, practical palladium-catalyzed cyanation of (hetero)aryl chlorides and bromides.

    Science.gov (United States)

    Senecal, Todd D; Shu, Wei; Buchwald, Stephen L

    2013-09-16

    Playing it safe: The nontoxic cyanide source K4 [Fe(CN)6]·3H2O can be used for the cyanation of (hetero)aryl halides. The application of palladacycle catalysts prevents poisoning during catalyst formation, thereby allowing for low catalyst loadings, fast reaction times, and wide heterocyclic substrate scope. PMID:23934947

  14. Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

    OpenAIRE

    Bou-hamdan, Farhan R.; Le?vesque, Franc?ois; O Brien, Alexander G.; Seeberger, Peter H.

    2011-01-01

    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.

  15. Enantioselective Arylative Dearomatization of Indoles via Pd-Catalyzed Intramolecular Reductive Heck Reactions.

    Science.gov (United States)

    Shen, Chong; Liu, Ren-Rong; Fan, Ren-Jie; Li, Ying-Long; Xu, Teng-Fei; Gao, Jian-Rong; Jia, Yi-Xia

    2015-04-22

    A highly enantioselective intramolecular arylative dearomatization of indoles via palladium-catalyzed reductive Heck reactions was developed. The new strategy led to a series of optically active indolines bearing C2-quaternary stereocenters in modest to good yields with excellent enantioselectivities (up to 99% ee). PMID:25849154

  16. Efficient and Simple Synthesis of 6-Aryl-1,4-dimethyl-9H-carbazoles

    Directory of Open Access Journals (Sweden)

    Sylvain Rault

    2008-06-01

    Full Text Available A synthetic method for the preparation of 6-aryl-1,4-dimethyl-9H-carbazoles involving a palladium catalyzed coupling reaction of 1,4-dimethyl-9H-carbazole-6-boronic acids and (heteroaryl halides is described.

  17. Pd(0) -Catalyzed Intramolecular ?-Arylation of Sulfones: Domino Reactions in the Synthesis of Functionalized Tetrahydroisoquinolines.

    Science.gov (United States)

    Solé, Daniel; Pérez-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

  18. An aryl-thioether substituted nitrobenzothiadiazole probe for the selective detection of cysteine and homocysteine.

    Science.gov (United States)

    Lee, Dayoung; Kim, Gyoungmi; Yin, Jun; Yoon, Juyoung

    2015-03-31

    An aryl-thioether substituted nitrobenzothiadiazole probe was synthesized and employed to detect cysteine and homocysteine selectively in living cells. Interestingly, both cysteine (Cys) and homocysteine (Hcy) promote an enhancement of the fluorescence intensity of the probe at pH 7.4 while only Cys gives rise to this enhancement under weakly acidic conditions (pH 6.0). PMID:25773705

  19. Brønsted acid-surfactant (BAS catalysed cyclotrimerization of aryl methyl ketone

    Directory of Open Access Journals (Sweden)

    Kiran Phatangare

    2012-07-01

    Full Text Available A brønsted acid-surfactant catalysed and simple, mild, metal catalyst free and chemo-selective method has been developed for synthesis of 1, 3, 5-triaryl benzenes from aryl methyl ketones. The advantages of this protocol subsume green and sustainable reaction medium, mild reaction conditions, easy product recovery and its good yields.

  20. Kinetic Studies on the Structure-Reactivity Correlation of Aryl N-Phenyl Thioncarbamates

    International Nuclear Information System (INIS)

    In this work, we invoke the mechanistic criteria based on the sign of cross-interaction constants, ?XY where X and Y are the substituents in the nucleophile and substrate, respectively; for a stepwise mechanism the sign of ?XY was invariably positive and the reactivity-selectivity principle (RSP) was found to hold. Although there is abundant literature on the kinetics and mechanism of the aminolysis of aryl carbonates and esters, the aminolysis reactions of aryl carbamates have been less studied in terms of kinetics. The mechanism of the aminolysis of substituted diphenyl carbonates has been studied, and structure-reactivity relationships for those reactions have also been examined in detail by Gresser and Jencks. Castro and co-workers have reported a number of mechanistic studies on the aminolysis of aryl carbonates and esters. These and other studies showed that most of the aminolysis of aryl carbonates and esters proceed by either a stepwise mechanism through a zwitterionic tetrahedral intermediate, T±, or a concert mechanism depending on the amine, substrate, and solvent involved

  1. Inhibition of mucin glycosylation by aryl-N-acetyl-alpha-galactosaminides in human colon cancer cells

    International Nuclear Information System (INIS)

    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

  2. A stereoselective oxy-Michael route to protected beta-aryl-beta-hydroxy-alpha-amino acids

    OpenAIRE

    Hernandez-juan, Fa; Richardson, Rd; Dixon, Dj

    2006-01-01

    The stereoselective oxy-Michael addition of the 'naked' anion of (5)-6-methyl tetrahydropyran-2-ol to ?-nitro-?,?-unsaturated esters followed by reduction and in situ protection of the corresponding amine provides a new and efficient route to protected ?-aryl-?-hydroxy- ?-amino acids. © Georg Thieme Verlag Stuttgart.

  3. Copper-promoted reductive coupling of aryl iodides with 1,1,1-trifluoro-2-iodoethane.

    Science.gov (United States)

    Xu, Song; Chen, Huan-Huan; Dai, Jian-Jun; Xu, Hua-Jian

    2014-05-01

    An efficient Cu-promoted reductive coupling of aryl iodides with 1,1,1-trifluoro-2-iodoethane has been developed. This reaction could occur in good yields under milder conditions as compared with previous studies. The reaction tolerated nitro, formyl, ester, ether, carbonyl, sulfonyl, and even azo groups. PMID:24783963

  4. Palladium-Catalyzed ?-Arylation of Enones in the Synthesis of 2-Alkenylindoles and Carbazoles.

    Science.gov (United States)

    Kale, Ajit Prabhakar; Kumar, Gangam Srikanth; Mangadan, Arun Raj Kizhakkayil; Kapur, Manmohan

    2015-03-01

    A new unified strategy has been developed for the synthesis of substituted 2-alkenylindoles and carbazoles. The strategy uses palladium-catalyzed ?-arylation of TES-enol ethers of enones as the key step. The method is highly regioselective, provides good yields, and is expected to have wide application. PMID:25706978

  5. Ligand-Free, Palladium-Catalyzed Dihydrogen Generation from TMDS: Dehalogenation of Aryl Halides on Water.

    Science.gov (United States)

    Bhattacharjya, Anish; Klumphu, Piyatida; Lipshutz, Bruce H

    2015-03-01

    A mild and environmentally attractive dehalogenation of functionalized aryl halides has been developed using nanoparticles formed from PdCl2 in the presence of tetramethyldisiloxane (TMDS) on water. The active catalyst and reaction medium can be recycled. This method can also be applied to cascade reactions in a one-pot sequence. PMID:25679825

  6. Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

    Directory of Open Access Journals (Sweden)

    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.

  7. AN IMPROVED METHOD FOR THE DETERMINATION OF ARYL-4-HYDROXYLASE ACTIVITY

    Science.gov (United States)

    An improved method for separation of tritiated benzo(a) pyrene from tritiated water in the aryl-4-hydroxylase assay is presented. Quantitative retention of benzo(a) pyrene was obtained with mixed cellulose acetate and nitrate filters. Enzymatic activities obtained with this modif...

  8. Catalysis by palladium complexes: new prospects in amination of aryl and hetaryl chlorides

    Energy Technology Data Exchange (ETDEWEB)

    Abaev, V T [K. Khetagurov North-Ossetian State University, Vladikavkaz (Russian Federation); Serdyuk, O V [Leibniz-Institut fuer Katalyse an der Universitaet Rostock, Rostock (Germany)

    2008-02-28

    The main achievements in the chemistry of palladium-catalysed amination of chloroarenes are discussed. The general mechanism of the Buchwald-Hartwig reaction and the main types of catalytic systems used for the amination of aryl and hetaryl chlorides are considered.

  9. Mild Pd-catalyzed aminocarbonylation of (hetero)aryl bromides with a palladacycle precatalyst.

    Science.gov (United States)

    Friis, Stig D; Skrydstrup, Troels; Buchwald, Stephen L

    2014-08-15

    A palladacyclic precatalyst is employed to cleanly generate a highly active XantPhos-ligated Pd-catalyst. Its use in low temperature aminocarbonylations of (hetero)aryl bromides provides access to a range of challenging products in good to excellent yields with low catalyst loading and only a slight excess of CO. Some products are unattainable by traditional carbonylative coupling. PMID:25090373

  10. Rhodium-Catalyzed Asymmetric Arylation of Allyl Sulfones under the Conditions of Isomerization into Alkenyl Sulfones.

    Science.gov (United States)

    Lim, Kelvin Meng-Hui; Hayashi, Tamio

    2015-03-11

    The reaction of 3-sulfolene with arylboronic acids in the presence of a chiral diene-rhodium catalyst under highly basic conditions (10 equiv of KOH) gave high yields of 3-arylsulfolanes with high enantioselectivity, where 3-sulfolene is in equilibration with 2-sulfolene by base-catalyzed isomerization and the more reactive 2-sulfolene undergoes the rhodium-catalyzed asymmetric arylation. PMID:25706689

  11. Mechanochromic behavior of aryl-substituted buta-1,3-diene derivatives with aggregation enhanced emission.

    Science.gov (United States)

    Zhang, Yijia; Han, Ting; Gu, Shangzhi; Zhou, Tianye; Zhao, Chuanzhen; Guo, Yuexin; Feng, Xiao; Tong, Bin; Bing, J; Shi, Jianbing; Zhi, Junge; Dong, Yuping

    2014-07-14

    Three tetra-aryl substituted 1,3-butadiene derivatives with aggregation enhanced emission (AEE) and mechanochromic fluorescence behavior have been rationally designed and synthesized. The results suggest an effective design strategy for developing diverse materials with aggregation induced emission (AIE) and significant mechanochromic performance by employing D-?-A structures with large dipole moments. PMID:24920471

  12. An Electrochemical Synthesis of Functionalized Arylpyrimidines from 4-Amino-6-Chloropyrimidines and Aryl Halides

    Directory of Open Access Journals (Sweden)

    Eric Léonel

    2011-06-01

    Full Text Available A range of novel 4-amino-6-arylpyrimidines has been prepared under mild conditions by an electrochemical reductive cross-coupling between 4-amino-6-chloro-pyrimidines and functionalized aryl halides. The process, which employs a sacrificial iron anode in conjunction with a nickel(II catalyst, allows the formation of coupling products in moderate to high yields.

  13. Engaging nonaromatic, heterocyclic tosylates in reductive cross-coupling with aryl and heteroaryl bromides.

    Science.gov (United States)

    Molander, Gary A; Traister, Kaitlin M; O'Neill, Brian T

    2015-03-01

    A method has been developed for the introduction of nonaromatic heterocyclic structures onto aryl and heteroaryl bromides using alkyl tosylates in a reductive cross-coupling manifold. This protocol offers an improvement over previous methods by utilizing alkyl tosylate coupling partners that are bench-stable, crystalline solids that can be prepared from inexpensive, commercially available alcohols. PMID:25711834

  14. Magnetic silica supported palladium catalyst: synthesis of allyl aryl ethers in water

    Science.gov (United States)

    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...

  15. Hydrazone-palladium-catalyzed allylic arylation of cinnamyloxyphenylboronic acid pinacol esters.

    Science.gov (United States)

    Watanabe, Kohei; Mino, Takashi; Abe, Taichi; Kogure, Taketo; Sakamoto, Masami

    2014-07-18

    Allylic arylation of cinnamyloxyphenylboronic acid pinacol esters 3, which have arylboronic acid moiety and allylic ether moiety, using a hydrazone 1d-Pd(OAc)2 system proceeded and gave the corresponding 1,3-diarylpropene derivatives 4 with a phenolic hydroxyl group via a selective coupling reaction of the ?-allyl intermediate to the boron-substituted position of the leaving group. PMID:24962496

  16. Enantioselective carbocycle formation through intramolecular Pd-catalyzed allyl-aryl cross-coupling.

    Science.gov (United States)

    Schuster, Christopher H; Coombs, John R; Kasun, Zachary A; Morken, James P

    2014-09-01

    Aryl electrophiles containing tethered allylboronate units undergo efficient intramolecular coupling in the presence of a chiral palladium catalyst to give enantioenriched carbocyclic products. The reaction is found to be quite general, affording 5, 6, and 7-membered carbocyclic products as single regioisomers and with moderate enantioselectivities. Examination of differential coupling partners points to rapid allyl-equilibration as a key stereodefining feature. PMID:25105510

  17. Ligand selectivity and gene regulation by the human aryl hydrocarbon receptor in transgenic mice.

    Science.gov (United States)

    Flaveny, Colin A; Murray, Iain A; Chiaro, Chris R; Perdew, Gary H

    2009-06-01

    The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that displays interspecies differences with the human and mouse AHR C-terminal region sequences sharing only 58% amino acid sequence identity. Compared with the mouse AHR (mAHR), the human AHR (hAHR) displays approximately 10-fold lower relative affinity for prototypical AHR ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, which has been attributed to the amino acid residue valine 381 (alanine 375 in the mAHR) in the ligand binding domain of the hAHR. We investigated whether the 10-fold difference in ligand-binding affinity between the mAHR and hAHR would be observed with a diverse range of AHR ligands. To test this hypothesis, ligand binding assays were performed using the photo-affinity ligand 2-azido-3-[(125)I]iodo-7,8-dibromodibenzo-p-dioxin and liver cytosol isolated from hepatocyte-specific transgenic hAHR mice and C57BL/6J mice. It is noteworthy that competitive ligand-binding assays revealed that, compared with the mAHR, the hAHR has a higher relative affinity for certain compounds, including indirubin [(2Z)-2,3-biindole-2,3 (1'H,1'H)-dione and quercetin (2-(3,4dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one]. Electrophoretic mobility shift assays revealed that indirubin was more efficient at transforming the hAHR compared with the mAHR. Indirubin was also a more potent inducer of Cyp1a1 expression in transgenic hAHR mouse hepatocytes compared with C57BL/6J mouse hepatocytes. These observations suggest that indirubin is a potent hAHR ligand that is able to selectively bind to and activate the hAHR. These discoveries imply that there may be a significant degree of structural divergence between mAHR and hAHR ligands and highlights the importance of the hAHR transgenic mouse as a model to study the hAHR in vivo. PMID:19299563

  18. Ligand Selectivity and Gene Regulation by the Human Aryl Hydrocarbon Receptor in Transgenic MiceS?

    Science.gov (United States)

    Flaveny, Colin A.; Murray, Iain A.; Chiaro, Chris R.; Perdew, Gary H.

    2009-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that displays interspecies differences with the human and mouse AHR C-terminal region sequences sharing only 58% amino acid sequence identity. Compared with the mouse AHR (mAHR), the human AHR (hAHR) displays ?10-fold lower relative affinity for prototypical AHR ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, which has been attributed to the amino acid residue valine 381 (alanine 375 in the mAHR) in the ligand binding domain of the hAHR. We investigated whether the 10-fold difference in ligand-binding affinity between the mAHR and hAHR would be observed with a diverse range of AHR ligands. To test this hypothesis, ligand binding assays were performed using the photo-affinity ligand 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin and liver cytosol isolated from hepatocyte-specific transgenic hAHR mice and C57BL/6J mice. It is noteworthy that competitive ligand-binding assays revealed that, compared with the mAHR, the hAHR has a higher relative affinity for certain compounds, including indirubin [(2Z)-2,3-biindole-2,3 (1?H,1?H)-dione and quercetin (2-(3,4dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one]. Electrophoretic mobility shift assays revealed that indirubin was more efficient at transforming the hAHR compared with the mAHR. Indirubin was also a more potent inducer of Cyp1a1 expression in transgenic hAHR mouse hepatocytes compared with C57BL/6J mouse hepatocytes. These observations suggest that indirubin is a potent hAHR ligand that is able to selectively bind to and activate the hAHR. These discoveries imply that there may be a significant degree of structural divergence between mAHR and hAHR ligands and highlights the importance of the hAHR transgenic mouse as a model to study the hAHR in vivo. PMID:19299563

  19. Preparation of five- and six-coordinate aryl(hydrido) iridium(III) complexes from benzene and functionalized arenes by C-H activation.

    Science.gov (United States)

    Werner, Helmut; Höhn, Arthur; Dziallas, Michael; Dirnberger, Thomas

    2006-06-01

    The reaction of the in situ generated cyclooctene iridium(I) derivative trans-[IrCl(C8H14)(PiPr3)2] with benzene at 80 degrees C gave a mixture of the five-coordinate dihydrido and hydrido(phenyl) iridium(III) complexes [IrH2(Cl)(PiPr3)2] 2 and [IrH(C6H5)(Cl)(PiPr3)2] 3 in the ratio of about 1 : 2. The chloro- and fluoro-substituted arenes C6H5X (X = Cl, F), C6H4F2 and C6H4F(CH3) reacted also by C-H activation to afford the corresponding aryl(hydrido) iridium(III) derivatives [IrH(C6H4X)(Cl)(PiPr3)2] 7, 8, [IrH(C6H3F2)(Cl)(PiPr3)2] 9-11 and [IrH[C6H3F(CH3)](Cl)(PiPr3)2] 12, 13, respectively. The formation of isomeric mixtures had been detected by 1H, 13C, 19F and 31P NMR spectroscopy. Treatment of 3 and 7-13 with CO gave the octahedral carbonyl iridium(III) complexes [IrH(C6H3XX')(Cl)(CO)(PiPr3)2] 5, 14-20 without the elimination of the arene. The reactions of trans-[IrCl(C8H14)(PiPr3)2] with aryl ketones C6H5C(O)R (R = Me, Ph), aryl ketoximes C6H5C(NOH)R (R = Me, Ph) and benzaloxime C6H5C(NOH)H resulted in the formation of six-coordinate aryl(hydrido) iridium(III) compounds 21-25 with the aryl ligand coordinated in a bidentate kappa2-C,O or kappa2-C,N fashion. With C6H5C(O)NH2 as the substrate, the two isomers [IrH[kappa2-N,O-NHC(O)C6H5](Cl)(PiPr3)2] 26 and [IrH[kappa2-C,O-C6H4C(O)NH2](Cl)(PiPr3)2] 27 were prepared stepwise. Treatment of trans-[IrCl(C8H14)(PiPr3)2] with benzoic acid gave the benzoato(hydrido) complex [IrH[kappa2-O,O-O2CC6H5](Cl)(PiPr3)2] 29 which did not rearrange to the kappa2-C,O isomer. PMID:16718345

  20. Cooperation of structurally different aryl hydrocarbon receptor agonists and ?-catenin in the regulation of CYP1A expression.

    Science.gov (United States)

    Vaas, Sebastian; Kreft, Luisa; Schwarz, Michael; Braeuning, Albert

    2014-11-01

    The ligand-activated nuclear receptor AhR (aryl hydrocarbon receptor) mediates the response of hepatocytes to various exogenous compounds. AhR is classically activated by planar, aromatic hydrocarbons, but also by other, structurally rather unrelated compounds. Recent data show that the canonical Wnt/?-catenin signaling pathway is also involved in the regulation of hepatic zonal gene expression and drug metabolism in mammalian liver. Previous studies indicate that the loss of ?-catenin in hepatocytes diminishes the response to the AhR agonists 3-methylcholanthrene (3MC) in vivo and to 2,3,7,8-tetrachlorodibenzo-[p]-dioxin in vitro. The knockout of ?-catenin also impairs the zonal pattern of AhR target gene induction by 3MC. However, it is presently unknown whether the chemical nature of the AhR agonist influences the AhR/?-catenin interaction. Moreover, no information is available about the dose-response curves of AhR activation in the absence or presence of Wnt/?-catenin signaling. In the present study, we have analyzed AhR-dependent responses to different concentrations of structurally unrelated AhR agonists in vivo and in vitro. The results demonstrate that ?-catenin is essential to obtain the maximum AhR response. Moreover, using transgenic mouse models which allow for the ablation of ?-catenin at different age of mice, we demonstrate that the presence of ?-catenin, not postnatal developmental effects in ?-catenin-deficient livers, is responsible for the observed interplay of ?-catenin and the AhR. PMID:25174530

  1. Photoinduced Directional and Bidirectional Phase Transitions in Bistable Linear Polycyclic Aromatic Compounds

    Science.gov (United States)

    Zhang, Longlong; Yamamoto, Shoji

    2014-06-01

    We study photoinduced phase transitions in linear homocyclic and heterocyclic aromatic polymers, numerically solving the time-dependent Schrödinger equation and observing the photoinduced optical conductivity spectra along the way. All the polycyclic compounds of our interest have bistable cis–trans isomers, which are degenerate in energetics but distinct in optics, and therefore exhibit corresponding photochromism. We reveal that the molecular symmetry is decisive of the photoexchangeability of these bistable configurations, which is directional in molecules of the D2h geometry such as polyacene and paracyanogen but is bidirectional in those of the C2v geometry such as polypyridinopyridine and B, N-substituted acenes. We propose a series of polycyclic compounds for designing tunable photochromism of geometric origin.

  2. Compound odontoma

    OpenAIRE

    José Marcelo Vargas Pinto; Fábio Augusto Coelho de Oliveira; Cláudio Ferreira Nóia; Wagner Humberto Martins dos Santos

    2012-01-01

    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 bibliogra...

  3. Magnesium compounds

    Science.gov (United States)

    Kramer, D.A.

    2006-01-01

    In 2005, seawater and natural brines accounted for 51% of US magnesium compounds production. World magnesia production was estimated to be 14.5 Mt. Most of the production came from China, North Korea, Russia and Turkey. Although no specific production figures are available, Japan and the United States are estimated to account for almost one-half of the world's capacity from seawater and brines.

  4. Synthesis of 4-Aryl Substituted 3,4-Dihydropyrimidinones Using Silica-chloride Under Solvent Free Conditions

    Directory of Open Access Journals (Sweden)

    M P Kaushik

    2007-07-01

    Full Text Available This paper describes an improved procedure for the efficient and facile synthesis of 4-aryl substituted 3, 4-dihydropyrimidinones under mild reaction conditions with excellent yields using inexpensive silica chloride under solvent free conditions.

  5. Promotion of Organic Reactions by Ultrasound: Coupling of Alkyl and Aryl Halides in the Presence of Lithium Metal and Ultrasound.

    Science.gov (United States)

    Lash, Timothy D.; Berry, Donna

    1985-01-01

    Experiments involving the coupling of alkyl and aryl halides in the presence of lithium metal and ultrasound are described. The experiments illustrate classical Wurtz and Fittig reactions in addition to being a convenient application of organic sonochemistry. (JN)

  6. N-Heterocyclic carbene-catalyzed cyclocondensation of 2-aryl carboxylic acids and enones: highly enantioselective synthesis of ?-lactones.

    Science.gov (United States)

    Cheng, Jin-Tang; Chen, Xiang-Yu; Ye, Song

    2015-02-01

    The enantioselective N-heterocyclic carbene-catalyzed [4 + 2] cyclocondensation of 2-aryl carboxylic acids and enones was developed, affording the corresponding chiral ?-lactones in good yields with good diastereo- and high enantioselectivities. PMID:25485768

  7. Design, synthesis and biological evaluation of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine scaffold as DFG-out B-Raf kinase inhibitors.

    Science.gov (United States)

    Yang, Weimin; Chen, Yadong; Zhou, Xiang; Gu, Yazhou; Qian, Wenqi; Zhang, Fan; Han, Wei; Lu, Tao; Tang, Weifang

    2015-01-01

    By combining the scaffolds of UI-125 and Sorafenib, a series of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine moiety were designed and synthesized as novel DFG-out B-Raf(V600E) inhibitors. Among them, 20c-e, 20g and 21h displayed potent antiproliferative activities against melanoma A375 (B-Raf(V600E)) cell lines with IC50 values of 3.190, 2.276, 1.856, 1.632 ?M and 1.839 ?M, respectively, comparable with the positive control Vemurafenib (IC50 = 3.32 ?M). Selected compounds were tested for the ERK inhibition in human melanoma A375 (B-Raf(V600E)) and SK-MEL-2 (B-Raf(WT)) cell lines by Western blot. The results revealed that our compounds inhibited the proliferation of melanoma A375 cells (B-Raf(V600E)) through ERK pathway, without paradoxical activation of ERK in melanoma SK-MEL-2 cells (B-Raf(WT)). Eventually, 20g and 21h were selected to confirm their inhibitory effects on tumor growth in A375 xenograft models in mice. Compound 20g exhibited equivalent antitumor efficacy in vivo (T/C = 44.37%), compared to Sorafenib (T/C = 37.35%), by 23-day repetitive administration of a single dose of 50 mg/kg without significant body weight loss. PMID:25462267

  8. Quantitative analysis of aryl hydrocarbon receptor activation using fluorescence-based cell imaging--a high-throughput mechanism-based assay for drug discovery.

    Science.gov (United States)

    Garside, Helen; Stewart, Allison; Brown, Nick; Cooke, Emma-Louise; Graham, Mark; Sullivan, Michael

    2008-01-01

    Early identification of toxicity associated with new chemical entities is important for reducing compound attrition in late stage drug discovery. Activation of the aryl hydrocarbon receptor (AhR) by xenobiotics is a recognised mechanism of toxicity: the AhR mediates most, if not all, of the serious toxicities caused by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In addition to compounds such as TCDD, the AhR can be activated by compounds with drug-like properties; consequently there is a desire to eliminate AhR activity in candidate drug programs. Endogenous AhR translocates from the cytoplasm to the nucleus in response to prototypical AhR ligands. This trafficking was monitored in mouse Hepa-1 cells, human HepG2 cells and rat primary hepatocytes using an anti-AhR antibody. A confocal imaging plate reader, the InCell Analyzer 3000, was used to image fixed cells cultured in 96 well plates, and algorithms were used to analyse both population data and individual cell responses. The subsequent induction of the CYP1A1 gene, in the three cell models, was also assessed using quantitative real-time polymerase chain reaction and showed good correlation with the translocation assay. To conclude, we have established robust, automated high throughput assays for the identification of AhR activators in primary hepatocytes and cell lines. PMID:18098060

  9. The aryl hydrocarbon receptor-mediated and genotoxic effects of fractionated extract of standard reference diesel exhaust particle material in pulmonary, liver and prostate cells.

    Science.gov (United States)

    Pálková, Lenka; Vondrá?ek, Jan; Trilecová, Lenka; Ciganek, Miroslav; P?n?íková, Kate?ina; Ne?a, Ji?í; Milcová, Alena; Topinka, Jan; Machala, Miroslav

    2015-04-01

    Diesel exhaust particles (DEP) and the associated complex mixtures of organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), or their derivatives, have been suggested to exert deleterious effects on human health. We used a set of defined cellular models representing liver, lung and prostate tissues, in order to compare non-genotoxic and genotoxic effects of crude and fractionated extract of a standard reference DEP material - SRM 1650b. We focused on the aryl hydrocarbon receptor (AhR)-mediated activity, modulation of cell proliferation, formation of DNA adducts, oxidative DNA damage, and induction of DNA damage responses, including evaluation of apoptosis, and phosphorylation of p53 tumor suppressor and checkpoint kinases (Chk). Both PAHs and the polar aromatic compounds contributed to the AhR-mediated activity of DEP-associated organic pollutants. The principal identified AhR agonists included benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene, chrysene and several non-priority PAHs, including benzochrysenes and methylated PAHs. In contrast to PAHs, polar compounds contributed more significantly to overall formation of DNA adducts associated with phosphorylation of p53, Chk1 or Chk2, and partly with apoptosis. Therefore, more attention should be paid to identification of DEP-associated polar organic compounds, contributing to the AhR activation and cytotoxic/genotoxic effects of complex airborne mixtures of organic contaminants produced by diesel engines. PMID:25500124

  10. Determination of Trace Amounts of Highly Hydrophilic Compounds in Water by Direct Derivatization and Gas Chromatography - Mass Spectrometry

    OpenAIRE

    Pelizzetti, Ezio; Minero, Claudio; Vincenti, Marco

    1994-01-01

    A new procedure has been developed to derivatize a large set of highly hydrophilic substances ((poly) hydroxy and/or (poly)carboxylic acids, glycols and dihydroxybenzenes) directly in water. The key element of the method is the derivatizing agent used, n-hexyl chloroformate, which proved to be much more effective than other alkyl and aryl chloroformates. Detection limits in the low g/L range were found for most of the compounds studied, using positive ion chemical ionization mass spectrometry...

  11. Ligands derived from C-aryl substituted derivatives of cyclen: formation of kinetically unstable complexes with lanthanide(III) ions

    OpenAIRE

    Edlin, Cd; Faulkner, S.; Parker, D.; Wilkinson, Mp; Woods, M.; Lin, J.; Lasri, E.; Neth, F.; Port, M.

    1998-01-01

    The synthesis of C-aryl monosubstituted derivatives of 1,4,7,10-tetraazacyclododecane (cyclen) by metal templated reductive amination of triethylenetetramine with aryl glyoxals has been developed and shown to be widely applicable. Octadentate ligands derived from these C-substituted macrocycles form relatively labile eight-coordinate complexes, which dissociate when challenged with EDTA in aqueous solution at pH 5.5, suggesting their use in metal-transport processes rather than for applicatio...

  12. Facile Access to Sterically Hindered Aryl Ketones via Carbonylative Cross-Coupling: Application to the Total Synthesis of Luteolin

    OpenAIRE

    O’keefe, B. Michael; Simmons, Nicholas; Martin, Stephen F.

    2011-01-01

    A general and mild protocol for achieving the carbonylative cross-coupling of sterically-hindered, ortho-disubstituted aryl ketones is reported. The commercially available PEPPSI-IPr catalyst is shown to efficiently promote the carbonylative cross-coupling of hindered ortho-disubstituted aryl iodides to give diaryl ketones; traditional phosphine catalysts are less effective. Carbonylative Suzuki-Miyaura cross-couplings provide a diverse array of biaryl ketones in good to excellent yields. The...

  13. Ruthenium-catalyzed heteroatom-directed regioselective C-h arylation of indoles using a removable tether.

    Science.gov (United States)

    Tiwari, Virendra Kumar; Kamal, Neha; Kapur, Manmohan

    2015-04-01

    A new approach to C-2 arylated indoles has been developed by utilizing a ruthenium-catalyzed, heteroatom-directed regioselective C-H arylation. The reaction is highly site-selective and results in very good yields. The highlight of the work is the use of a removable directing group and compatibility of the catalytic system with halogen functional groups in the substrates. PMID:25764265

  14. Palladium-catalyzed hydroxylation of aryl and heteroaryl halides enabled by the use of a palladacycle precatalyst.

    Science.gov (United States)

    Cheung, Chi Wai; Buchwald, Stephen L

    2014-06-01

    A method for the hydroxylation of aryl and heteroaryl halides, promoted by a catalyst based on a biarylphosphine ligand tBuBrettPhos (L5) and its corresponding palladium precatalyst (1), is described. The reactions allow the cross-coupling of both potassium and cesium hydroxides with (hetero)aryl halides to afford a variety of phenols and hydroxylated heteroarenes in high to excellent yield. PMID:24762125

  15. Radical based strategy toward the synthesis of 2,3-dihydrofurans from aryl ketones and aromatic olefins.

    Science.gov (United States)

    Naveen, Togati; Kancherla, Rajesh; Maiti, Debabrata

    2014-10-17

    A copper-mediated annulation of aryl ketones with a wide range of aromatic olefins has been developed. This strategy allowed convenient access to 2,3-dihydrofuran derivatives. The versatility of the protocol is shown by synthesizing ?-methyl dihydrofurans, which serve as an intermediate for the synthesis of vitamin B1. In addition, the applicability of the protocol in conjugated systems is demonstrated. A radical pathway was presumed and supported for annulation of aryl ketones with olefins. PMID:25275799

  16. A simple preparation of Aryl Methansulfonates by Thermal Decomposition of Dry Arendiazonium o-Benzendisulfonimides in Methane Sulfonic acid

    OpenAIRE

    Fochi, Rita; Barbero, Margherita; Dughera, Stefano; Degani, Jacopo

    1999-01-01

    Aryl methanesulfonates (18 examples) were easily prepared by thermal decomposition of dry arenediazonium o-benzene-disulfonimides in methanesulfonic acid. The reactions were carried out at temperatures between 60 and 120 °C for times between 0.5 and 8 h. The aryl methanesulfonates were obtained in reproducible yield of 70-90%, with few exceptions. In all cases the o-benzenedisulfonimide could be recovered in good yields which can then be reused to prepare the salts. When thermal decompositio...

  17. Experimental prophylaxis and therapy of radiation damage by newly synthesized S-heteryl mercaptoalkyl N-aryl hydrazidimides

    International Nuclear Information System (INIS)

    The synthesis is described of representatives of a new class of potential antiradiation agents, the S-heteryl mercaptoalkyl N-aryl hydrazidimides (MHA), obtained by molecular combination of three basic groups of radioprotectors. Toxicity characteristics (LD100, LD50, and maximum tolerable doses) indicated the compounds tested to be no more toxic for mide and rats than most of the established radioprotective agents. Under acute X-irradiation conditions with minimum absolutely lethal doses, 6 out of the 14 compounds tested showed clear-cut protective properties in mice. These 6 compounds also raised by 20 to 50% the survival of lethally irradiated rats. The most effective preparation was Y-64 (S-2-benzimidazolyl mercaptopropio N-p-tolyl hydrazidimide). This compound is observed to protect hematopoietic tissue in mice (Dose Reduction Factor of 1.29) and rats (Dose Reduction Factor of 1.52) given X-ray doses in the range of 400 to 900 R. With acute gamma irradiation, Y-64, as well as cysteamine, ensured survival of a larger amount of hematopoietic stem cells in bone marrow (using exogenous spleen colony techniques) and a more rapid recovery rate of the stem cell pool. With fractionated X-rays (5 x 100 R daily), Y-64 failed to increase survival, showing, nevertheless, a favorable effect on hematopoietic indices. When administered postradiation, Y-64 failed to influence the course of acute radiation disease in lethally irradiated mice; but, reducing hematopoietic damage, it raised by 40% the survival of lethally irradiated rats. No effect was observed with Y-64 post treatment following either fractionated irradiation (15 x 100 R daily) given to rats or prolonged gamma irradiation (0.28 R/min) to mice. Studies to shed light on the mechanism of action of MHA indicated that antiradiation-active representatives of the class have lower activation energy of oxidation values and produce functional changes in the thyroid (iodine-131 incorporation reduction), as compared with ineffective representatives. From the experimental data obtained, it may be presumed that mechanisms underlying MHA protective action operate essentially via the oxygen effect. (A.B.)

  18. Microwave Assisted Synthesis of 1-[5-(Substituted Aryl-1H-Pyrazol-3-yl]-3,5-Diphenyl-1H-1,2,4-Triazole as Antinociceptive and Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Shantaram Gajanan Khanage

    2014-05-01

    Full Text Available Purpose: An efficient technique has been developed for microwave assisted synthesis of 1-[5-(substituted aryl-1H-pyrazol-3-yl]-3,5-diphenyl-1H-1,2,4-triazole as antinociceptive and antimicrobial agents. Methods: The desired compounds (S1-S10 were synthesized by the microwave irradiation via cyclization of formerly synthesized chalcones of 3,5-diphenyl-1H-1,2,4-triazole and hydrazine hydrate in mild acidic condition. All newly synthesized compounds were subjected to study their antinociceptive and antimicrobial activity. The analgesic potential of compounds was tested by acetic acid induced writhing response and hot plate method. The MIC values for antimicrobial activity were premeditated by liquid broth method. Results: The compounds S1, S2, S4, S6 and S10 were found to be excellent peripherally acting analgesic agents when tested on mice by acetic acid induced writhing method and compounds S3, S6 and S1 at dose level of 100 mg/kg were exhibited superior centrally acting antinociceptive activity when tested by Eddy’s hot plate method. In antimicrobial activity compound S10 found to be broad spectrum antibacterial agent at MIC value of 15.62 ?g/ml and compound S6 was exhibited antifungal potential at 15.62 ?g/mL on both fungal strains. Conclusion: Some novel pyrazoles clubbed with 1,2,4-triazole derivatives were synthesized and evaluated as possible antimicrobial, centrally and peripherally acting analgesics.

  19. Rh(I)-Catalyzed Arylation of Heterocycles via C-H Bond Activation: Expanded Scope Through Mechanistic Insight

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Spectroscopic, structural, computational and (spectro)electrochemical studies of icosahedral carboranes bearing fluorinated aryl groups.

    Science.gov (United States)

    Tricas, Hugo; Colon, Marta; Ellis, David; Macgregor, Stuart A; McKay, David; Rosair, Georgina M; Welch, Alan J; Glukhov, Ivan V; Rossi, Fulvio; Laschi, Franco; Zanello, Piero

    2011-04-28

    The icosahedral carboranes 1-C(6)F(5)-2-Ph-1,2-closo-C(2)B(10)H(10) (1), 1-(4'-F(3)CC(6)H(4))-2-Ph-1,2-closo-C(2)B(10)H(10) (2), 1,2-(4'-F(3)CC(6)H(4))(2)-1,2-closo-C(2)B(10)H(10) (3), 1-(4'-H(3)CC(6)F(4))-2-Ph-1,2-closo-C(2)B(10)H(10) (4), 1-(4'-F(3)CC(6)F(4))-2-Ph-1,2-closo-C(2)B(10)H(10) (5), 1,2-(4'-F(3)CC(6)F(4))(2)-1,2-closo-C(2)B(10)H(10) (6), 1,7-(4'-F(3)CC(6)F(4))(2)-1,7-closo-C(2)B(10)H(10) (7) and 1,12-(4'-F(3)CC(6)F(4))(2)-1,12-closo-C(2)B(10)H(10) (8), with fluorinated aryl substituents on cage carbon atoms, have been prepared in good to high yields and characterised by microanalysis, (1)H, (11)B and (19)F NMR spectroscopies, mass spectrometry, single-crystal X-ray diffraction and (spectro)electrochemistry. By analysis of , the weighted average (11)B chemical shift, a ranking order for the ortho carboranes 1-6 is established based on the combined electron-withdrawing properties of the C-substituents, and is in perfect agreement with that established independently by electrochemical study. In a parallel computational study the effects of a wide range of different substituents on the redox properties of carboranes have been probed by comparison of ?E values, where ?E is the energy gap between the DFT-optimised [7,9-R(2)-7,9-nido-C(2)B(10)](2-) anion and its DFT-optimised basket-shaped first oxidation product. The overall conclusion from the NMR spectroscopic, electrochemical and computational studies is that strongly electron withdrawing substituents significantly stabilise [7,9-nido-C(2)B(10)](2-) dianions with respect to oxidation, and that the best practical substituent is 4-F(3)CC(6)F(4). Thus attention focussed on the reduction of 1,2-(4'-F(3)CC(6)F(4))(2)-1,2-closo-C(2)B(10)H(10), compound 6. The sequence 6/[6](-)/[6](2-) appears reversible on the cyclic voltammetric timescale but on the longer timescale of macroelectrolysis the radical anion is only partially stable. EPR study of the electrogenerated monoanions from the ortho-carboranes 1-6 confirms the cage-centred nature of the redox processes. In contrast, the reduction of the meta- and para-carboranes 7 and 8, respectively, appears to be centred on the aromatic substituents, a conclusion supported by the results of DFT calculation of the LUMOs of compounds 6-8. Bulk 2-electron reduction of 6 affords a dianion which is remarkably stable to reoxidation, surviving for several hours in the open laboratory in the absence of halogenated solvents. PMID:21390395

  1. Azo-hydrazone tautomerism of aryl azo pyridone dyes

    OpenAIRE

    Mirkovi? Jelena M.; Uš?umli? Gordana S.; Marinkovi? Aleksandar D.; Z?, Mijin Dus?an

    2013-01-01

    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 max...

  2. Intermetallic Compounds

    Science.gov (United States)

    Takagiwa, Y.; Matsuura, Y.; Kimura, K.

    2014-06-01

    We have focused on the binary narrow-bandgap intermetallic compounds FeGa3 and RuGa3 as thermoelectric materials. Their crystal structure is FeGa3-type (tetragonal, P42/ mnm) with 16 atoms per unit cell. Despite their simple crystal structure, their room temperature thermal conductivity is in the range 4-5-W-m-1-K-1. Both compounds have narrow-bandgaps of approximately 0.3-eV near the Fermi level. Because their Seebeck coefficients are quite large negative values in the range 350-<-| S 373K|-<-550- ?V-K-1 for undoped samples, it should be possible to obtain highly efficient thermoelectric materials both by adjusting the carrier concentration and by reducing the thermal conductivity. Here, we report the effects of doping on the thermoelectric properties of FeGa3 and RuGa3 as n and p-type materials. The dimensionless figure of merit, ZT, was significantly improved by substitution of Sn for Ga in FeGa3 (electron-doping) and by substitution of Zn for Ga in RuGa3 (hole-doping), mainly as a result of optimization of the electronic part, S 2 ?.

  3. Bitumen compounds

    Energy Technology Data Exchange (ETDEWEB)

    Koga, K.

    1981-11-19

    Bitumen compounds (BK) are patented, which have high mechanical strength and are produced through mixing bitumen (Bm) and fillers (Np) and residues from the production of acetylene (OPA) from calcium carbide. The bitumen compound includes 3 to 8 percent bitumen of direct distillation or oxidized bitumen; 85 to 93.5 percent of the first filler (sand, roasted china clay or pearlite); 0.1 to 10 percent of the second filler (finely dispersed bank sand, clay, calcium carbonate, talc) and 0.1 to 10 percent of the acetylene production residues. Example. Appropriate quantities of the directly distilled bitumen (grade 60 to 80) with a specific weight of 1.020, a softening point of 48 degrees and a relative elongation at 15 degrees of more than 150 percent are mixed at a temperature of 150 to 155 degrees with the first and second fillers and are pressed in a cylindrical press mold with a diameter of 100 millimeters and a height of 62.5 millimeters.

  4. n participation and secondary deuterium isotope effects in solvolysis of 1-aryl-4-methoxy-1-butyl chlorides. Are there two distinct k/sub ?/ pathways

    International Nuclear Information System (INIS)

    A series of 1-aryl-4-methoxy-1-butyl chlorides (3) and their 1-d and 2,2-d2 analogues were prepared and the solvolysis rates measured. All compounds show rate accelerations relative to the corresponding 1-aryl-1-alkyl chlorides. The results indicate that k/sub ?/ is the main pathway, except possibly for the p-anisyl derivative. ?-deuterium isotope effects increase from k/sub H//k/sub D/ = 0.97 to 1.10 with decreasing sigma+ of the phenyl substituent and/or with increasing ionizing power of the solvent. Such results are indicative of a change in mechanism and can best be accommodated by assuming two distinct k/sub ?/ pathways. The first, operative in cases when an ?-deuterium effect of about unity is observed, is the internal direct displacement of the chloride by the methoxy group, yielding an oxonium ion intermediate (5). The other k/sub ?/ pathway involves a rate-determining ionization into an intimate ion pair (10) which is then converted into 5 in a fast process. With the p-anisyl derivative the 10 to 5 conversion process becomes rate determining, competing with further ionization of 10 into a solvent-separated ion pair (k/sub c/ process). The observed small ?-deuterium isotope effects are consistent with such a mechanism except that they appear to be about 3 to 4% too low for a rate-determining ionization to 10. This observation can be explained if it is assumed that there is an interaction between the aliphatic methoxyl and the carbenhe aliphatic methoxyl and the carbenium ion center in 10, restricting the motions of the side chain and forcing C2-H(D) bonding orbitals into a geometry unfavorable to hyperconjugative electron release. The main defect of the proposed mechanism is a lack of analogy to the corresponding ? participation

  5. Altered Subcellular Localization of Heat Shock Protein 90 Is Associated with Impaired Expression of the Aryl Hydrocarbon Receptor Pathway in Dogs

    OpenAIRE

    Steenbeek, Frank G.; Spee, Bart; Penning, Louis C.; Kummeling, Anne; Gils, Ingrid H. M.; Grinwis, Guy C. M.; Leenen, Dik; Holstege, Frank C. P.; Vos-loohuis, Manon; Rothuizen, Jan; Leegwater, Peter A. J.

    2013-01-01

    The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting protein (AIP) and aryl hydrocarbon receptor nuclear translocator (ARNT). The resulting intrahepatic portosystemic shunts (IHPSS) are frequently diagnosed in specific dog breeds, such as the Irish wolfhoun...

  6. Microwave-enhanced alpha-arylation of a protected glycine in water: evaluation of 3-phenylglycine derivatives as inhibitors of the tuberculosis enzyme, glutamine synthetase.

    Science.gov (United States)

    Lagerlund, Olof; Odell, Luke R; Mowbray, Sherry L; Nilsson, Mikael T; Krajewski, Wojciech W; Nordqvist, Anneli; Karlén, Anders; Larhed, Mats

    2007-11-01

    A microwave-enhanced, palladium-catalyzed protocol for the alpha-arylation of a protected glycine in neat water is described. This reaction proceeds rapidly, under non-inert conditions, to afford a range of phenylglycine derivatives in moderate to good yields. Based on this alpha-arylation, a number of aryl L-methionine-SR-sulfoximine (MSO) analogues were prepared and evaluated for their Mycobacterium tuberculosis glutamine synthetase (TB-GS) inhibitory activity. PMID:18478959

  7. 1,4,8,11-Tetra[2-aryl-1-diazenyl]-1,4,8,11-tetraazacyclotetradecanes - synthesis, characterization, and x-ray crystallography of the first tetrakistriazenes to be reported

    International Nuclear Information System (INIS)

    The reactions of a series of arene diazonium salts with 1,4,8,11-tetraazacyclotetradecane (cyclam) afford the novel compounds, the 1,4,8,11-tetra[2-aryl-1-diazenyl]-1,4,8,11-tetraazacyclotetradecanes (1a-1f), which are the first examples of tetrakistriazenes to be reported. The tetrakistriazenes were characterized by IR spectroscopy, proton and carbon NMR, elemental analysis, high resolution electrospray mass spectrometry, and X-ray crystallography. The analogous reaction of a diazonium salt with 1,4,7-triazacyclononane or 1,5,9-triazacyclododecane yields the tristriazenes 2, 3a, and 3b. The structures of compounds 1c and 1e were solved by X-ray crystallography at low temperature (150 K). Both molecules display a conformation where the four phenyltriazenyl groups point alternately upwards and downwards with respect to the mean macrocyclic plane. (author)

  8. Copper(II) complexes of bis(aryl-imino)acenaphthene ligands: synthesis, structure, DFT studies and evaluation in reverse ATRP of styrene.

    Science.gov (United States)

    Fliedel, Christophe; Rosa, Vitor; Santos, Carla I M; Gonzalez, Pablo J; Almeida, Rui M; Gomes, Clara S B; Gomes, Pedro T; Lemos, M Amélia N D A; Aullón, Gabriel; Welter, Richard; Avilés, Teresa

    2014-09-14

    Two new Ar-BIAN Cu(II) complexes (where Ar-BIAN = bis(aryl-imino)acenaphthene) of formulations [CuCl2(Mes-BIAN)] (1) (Mes = 2,4,6-Me3C6H2) and [CuCl2(Dipp-BIAN)] (2) (Dipp = 2,6-iPr2C6H3) were synthesised by direct reaction of CuCl2 suspended in dichloromethane with the respective ligands Mes-BIAN (L1) and Dipp-BIAN (L2), dissolved in dichloromethane, under an argon atmosphere. Attempts to obtain these compounds by solubilising CuCl2 in methanol and adding a dichloromethane solution of the corresponding ligand, under aerobic conditions, gave also compound 1, but, in the case of L2, the Cu(I) dimer [CuCl(Dipp-BIAN)]2 (3) was obtained instead of compound 2. The compounds were fully characterised by elemental analyses, MALDI-TOF mass spectrometry, FT-IR, (1)H NMR and EPR spectroscopic techniques. The solid-state molecular structures of compounds 1-3 were determined by single crystal X-ray diffraction, showing the expected chelation of the Ar-BIAN ligands and two chloride ligands completing the coordination sphere of the Cu(II) centre. In the case of the complex 1, an intermediate coordination geometry around the Cu(II) centre, between square planar and tetrahedral, was revealed, while the complex 2 showed an almost square planar geometry. The structural differences and evaluation of energetic changes were rationalised by DFT calculations. Analysis of the electrochemical behaviour of complexes 1-3 was performed by cyclic voltammetry and the experimental redox potentials for Cu(II)/Cu(I) pairs have been compared with theoretical values calculated by DFT in the gas phase and in dichloromethane and methanol solutions. The complex 1 exhibited good activity in the reverse atom transfer radical polymerisation (ATRP) of styrene. PMID:25036889

  9. Ligand-Enabled Reactivity and Selectivity in a Synthetically Versatile Aryl C–H Olefination*

    Science.gov (United States)

    Wang, Dong-Hui; Engle, Keary M.; Shi, Bing-Feng; Yu, Jin-Quan

    2010-01-01

    The Mizoroki–Heck reaction, which couples aryl halides with olefins, has been widely used to stitch together the carbogenic cores of numerous complex organic molecules. Given that the position-selective introduction of a halide onto an arene is not always straightforward, direct olefination of aryl C–H bonds would obviate the inefficiencies associated with generating halide precursors or their equivalents; however, methods for carrying out such a reaction have suffered from narrow substrate scope and low positional selectivity. Here we report an operationally simple, atom-economical, carboxylate-directed Pd(II)-catalyzed C–H olefination reaction with phenylacetic acid and 3-phenylpropionic acid substrates, using oxygen at atmospheric pressure as the oxidant. The positional selectivity can be tuned by introducing amino acid derivatives as ligands. We demonstrate the versatility of the method through direct elaboration of commercial drug scaffolds and efficient synthesis of 2-tetralone and naphthoic acid natural product cores. PMID:19965380

  10. A novel poly(aryl ether) containing azobenzene chromophore and pendant oligoaniline: Synthesis and electrochromic properties

    International Nuclear Information System (INIS)

    Graphical abstract: This work describes a novel poly(aryl ether) functionalized with azobenzene chromophore and pendant oligoaniline, that exhibits a satisfied electrochromic properties with high contrast value, good coloration efficiency, moderate switching times and acceptable stability. - Abstract: A novel poly(aryl ether), containing pendant oligoaniline and azobenzene moieties (Azo-PAE-p-OA), was synthesized by nucleophilic polycondensation. The structures were confirmed spectroscopically via nuclear magnetic resonance (NMR) and Fourier-transform infrared spectra (FTIR), morphological data was ascertained via X-ray diffraction (XRD), and the thermal stability was probed via thermogravimetric analysis (TGA). Due to the coexistence of oligoaniline and azobenzene groups, Azo-PAE-p-OA shows reversible electroactivity and expectable photoresponse to light irradiation, chemical redox and electrochemical modulation. The electrochromic performance of a Azo-PAE-p-OA film on indium tin oxide (ITO) was investigated by spectrochronoamperometry, and exhibited electrochromic properties with high contrast value, good coloration efficiency, moderate switching times, and acceptable stability.

  11. Ligand-Enabled ?-C-H Arylation of ?-Amino Acids Using a Simple and Practical Auxiliary.

    Science.gov (United States)

    Chen, Gang; Shigenari, Toshihiko; Jain, Pankaj; Zhang, Zhipeng; Jin, Zhong; He, Jian; Li, Suhua; Mapelli, Claudio; Miller, Michael M; Poss, Michael A; Scola, Paul M; Yeung, Kap-Sun; Yu, Jin-Quan

    2015-03-11

    Pd-catalyzed ?-C-H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to the most widely used auxiliaries in asymmetric synthesis, the simplicity and practicality of the auxiliaries developed for C-H activation remains to be improved. We previously developed a simple N-methoxyamide auxiliary to direct ?-C-H activation, albeit this system was not compatible with carboxylic acids containing ?-hydrogen atoms. Herein we report the development of a pyridine-type ligand that overcomes this limitation of the N-methoxyamide auxiliary, leading to a significant improvement of ?-arylation of carboxylic acid derivatives, especially ?-amino acids. The arylation using this practical auxiliary is applied to the gram-scale syntheses of unnatural amino acids, bioactive molecules, and chiral bis(oxazoline) ligands. PMID:25697780

  12. Aryl-derivatized, water-soluble functionalized carbon nanotubes for biomedical applications

    International Nuclear Information System (INIS)

    The functionalization of very-thin multi-walled carbon nanotubes (VT-MWNTs) with an aniline derivative, via the protocol of in situ generated aryl diazonium salts results, upon acidic deprotection of the terminal BOC group, on the formation of the water-soluble positively charged ammonium functionalized VT-MWNTs-NH3+ material. The new materials have been structurally and morphologically characterized by infra-red (ATR-IR) spectroscopy and transmission electron microscopy (TEM). The quantitative calculation of the grafted aryl units onto the skeleton of VT-MWNTs has been estimated by thermogravimetric analysis (TGA), while the quantitative Kaiser test showed the amine group loaded onto VT-MWNTs-NH3+ material. The aqueous solubility of this material has allowed the performance of some initial toxicological in vitro investigations

  13. Synthesis of N-Aryl-2-allyl Pyrrolidines via Palladium-catalyzed Carboamination Reactions of ?-(N-Arylamino)alkenes with Vinyl Bromides

    OpenAIRE

    Ney, Joshua E.; Hay, Michael B.; Yang, Qifei; Wolfe, John P.

    2005-01-01

    A palladium-catalyzed carboamination reaction of ?-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 ?-amino alkene, an aryl bromide, and a vinyl bromide are al...

  14. Copper(II)-mediated O-arylation of protected serines and threonines.

    Science.gov (United States)

    El Khatib, Mirna; Molander, Gary A

    2014-09-19

    An effective protocol toward the O-arylation of ?-hydroxy-?-amino acid substrates serine and threonine has been developed via Chan-Lam cross-coupling. This Cu(II)-catalyzed transformation involves benign open-flask conditions that are well-tolerated with a variety of protected (Boc-, Cbz-, Tr-, and Fmoc-) serine and threonine derivatives and various potassium organotrifluoroborates and boronic acids. PMID:25208062

  15. Synthesis of (-)-(S,S)-clemastine by invertive N --> C aryl migration in a lithiated carbamate.

    Science.gov (United States)

    Fournier, Anne M; Brown, Robert A; Farnaby, William; Miyatake-Ondozabal, Hideki; Clayden, Jonathan

    2010-05-21

    The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of alpha-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement. PMID:20405879

  16. Corrigendum to Solvent-dependent oxidative coupling of 1-aryl-1,3-dicarbonyls and styrene

    Science.gov (United States)

    Casey, Brian M.; Eakin, Cynthia A.; Jiao, Jingliang; Sadasivam, Dhandapani V.

    2010-01-01

    This report describes the scope and mechanism of the solvent-dependent, chemoselective oxidative coupling of 1-aryl-1,3-dicarbonyls with styrene using Ce(IV) reagents. Dihydrofuran derivatives are obtained when reactions are performed in methanol whereas nitrate esters can be selectively synthesized in acetonitrile and methylene chloride. Mechanistic studies are consistent with the rate of solvent-assisted deprotonation of a radical cation intermediate playing an integral role in the selective formation of products. PMID:20806051

  17. Solvent-dependent oxidative coupling of 1-aryl-1,3-dicarbonyls and styrene

    Science.gov (United States)

    Casey, Brian M.; Eakin, Cynthia A.; Jiao, Jingliang; Sadasivam, Dhandapani V.; Flowers, Robert A.

    2009-01-01

    This report describes the scope and mechanism of the solvent-dependent, chemoselective oxidative coupling of 1-aryl-1,3-dicarbonyls with styrene using Ce(IV) reagents. Dihydrofuran derivatives are obtained when reactions are performed in methanol whereas ?-tetralones can be selectively synthesized in acetonitrile and methylene chloride. Mechanistic studies are consistent with the rate of solvent-assisted deprotonation of a radical cation intermediate playing an integral role in the selective formation of products. PMID:20625455

  18. Copper-catalyzed tandem annulation/arylation for the synthesis of diindolylmethanes from propargylic alcohols.

    Science.gov (United States)

    Li, Hui; Li, Xiaoxun; Wang, Hao-Yuan; Winston-McPherson, Gabrielle N; Geng, Hao-miao Julie; Guzei, Ilia A; Tang, Weiping

    2014-10-21

    Various highly substituted 2,3'-diindolylmethane heterocycles were prepared from propargylic alcohols and indole nucleophiles via a transition metal-catalyzed tandem indole annulation/arylation reaction for the first time. Among the metal catalysts we examined, the most economical copper(I) catalyst provided the highest efficiency. The indole nucleophiles could also be replaced by other electron-rich arenes or alcohols. PMID:25178910

  19. Agonist and Chemopreventative Ligands Induce Differential Transcriptional Cofactor Recruitment by Aryl Hydrocarbon Receptor

    OpenAIRE

    Hestermann, Eli V.; Brown, Myles

    2003-01-01

    Aryl hydrocarbon receptor (AHR) is a transcription factor whose activity is regulated by environmental agents, including several carcinogenic agonists. We measured recruitment of AHR and associated proteins to the human cytochrome P4501A1 gene promoter in vivo. Upon treatment with the agonist ?-naphthoflavone, AHR is rapidly associated with the promoter and recruits the three members of the p160 family of coactivators as well as the p300 histone acetyltransferase, leading to recruitment of R...

  20. One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol.

    Science.gov (United States)

    Kyne, Sara H; Percy, Jonathan M; Pullin, Robert D C; Redmond, Joanna M; Wilson, Peter G

    2011-12-21

    Difluoroalkenylzinc reagents prepared from 1-(2'-methoxy-ethoxymethoxy)-2,2,2-trifluoroethane and 1-(N,N-diethylcarbamoyloxy)-2,2,2-trifluoroethane at ice bath temperatures underwent Negishi coupling with a range of aryl halides in a convenient one pot procedure. While significant differences between the enol acetal and carbamate reagents were revealed, the Negishi protocol compared very favourably with alternative coupling procedures in terms of overall yields from trifluoroethanol. PMID:22064968

  1. Ligand Selectivity and Gene Regulation by the Human Aryl Hydrocarbon Receptor in Transgenic MiceS?

    OpenAIRE

    Flaveny, Colin A.; Murray, Iain A.; Chiaro, Chris R.; Perdew, Gary H.

    2009-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that displays interspecies differences with the human and mouse AHR C-terminal region sequences sharing only 58% amino acid sequence identity. Compared with the mouse AHR (mAHR), the human AHR (hAHR) displays ?10-fold lower relative affinity for prototypical AHR ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, which has been attributed to the amino acid residue valine 381 (alanine 375 ...

  2. Evidence for Ligand-Mediated Selective Modulation of Aryl Hydrocarbon Receptor ActivityS?

    OpenAIRE

    Murray, Iain A.; Morales, Jose L.; Flaveny, Colin A.; Dinatale, Brett C.; Chiaro, Chris; Gowdahalli, Krishnegowda; Amin, Shantu; Perdew, Gary H.

    2010-01-01

    The concept of selective receptor modulators has been established for the nuclear steroid hormone receptors. Such selective modulators have been used therapeutically with great success in the treatment of cancer. However, this concept has not been examined with regard to the aryl hydrocarbon receptor (AHR) because of the latent toxicity commonly associated with AHR activation. AHR-mediated toxicity is primarily derived from AHR binding to its dioxin response element (DRE) and driving expressi...

  3. Highly efficient and reusable supported pd catalysts for Suzuki-Miyaura reactions of aryl chlorides.

    Science.gov (United States)

    Schweizer, Stéphane; Becht, Jean-Michel; Le Drian, Claude

    2007-09-13

    Syntheses of air- and moisture-stable heterogeneous (tert-butylarylphosphino)polystyrene-supported Pd catalysts and their use for versatile Suzuki-Miyaura reactions of aryl chlorides and arylboronic acids under non-anhydrous conditions are reported. The catalysts are easily recovered by filtration. They can be used many times (more than seven) without showing any loss of activity, and the amount of Pd leached is extremely low (<0.1%). PMID:17715929

  4. Spectral and catalytic properties of aryl-alcohol oxidase, a fungal flavoenzyme acting on polyunsaturated alcohols

    OpenAIRE

    Ferreira, P.; Medina, M.; Guille?n, F.; Marti?nez, M. J.; Berkel, W. J. H.; Marti?nez, A. T.

    2005-01-01

    Spectral and catalytic properties of the flavoenzyme AAO (aryl-alcohol oxidase) from Pleurotus eryngii were investigated using recombinant enzyme. Unlike most flavoprotein oxidases, AAO does not thermodynamically stabilize a flavin semiquinone radical and forms no sulphite adduct. AAO catalyses the oxidative dehydrogenation of a wide range of unsaturated primary alcohols with hydrogen peroxide production. This differentiates the enzyme from VAO (vanillyl-alcohol oxidase), which is specific fo...

  5. Photoinduced intramolecular substitution reaction of aryl halide with carbonyl oxygen of amide group

    CERN Document Server

    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.

  6. Theoretical studies of palladium-catalyzed cycloaddition of alkynyl aryl ethers and alkynes.

    Science.gov (United States)

    Meng, Qingxi; Wang, Fen

    2014-12-01

    Density functional theory (DFT) was used to investigate palladium(0)-catalyzed cycloaddition of alkynyl aryl ethers and alkynes to generate 2-methylidene-2H-chromenes. Calculations indicated that the cycloaddition had five possible reaction pathways: I, II, III, IV, and V. In the palladium(0)-alkynyl aryl ether complex IM1, the oxidative addition of the Caryl-H bond occurred prior to the dissociation of a ligand PMe3. The dissociation of a ligand PMe3 from the five-coordinated complex IM2 was much easier to achieve than the hydrogen transfer reaction and the substitution reaction of alkynes. In the palladium(0)-hydride complex IM4, the hydrogen migration of H1 from palladium to carbon C1 was much easier to achieve than migration to carbon C2. In the four-coordinated aryl-palladium-alkyne complexes IM6a and IM6b, the alkyne insertion reaction into the Pd-Caryl bond occurred prior to that into the Pd-Calkenyl bond. The reaction channel IM1???TS1???IM2???IM4???TS3a???IM5a???IM6a???TS4a1???IM7a1???TS5a1???IM8a was the most favorable among the catalytic reaction pathways of the cycloaddition of alkynyl aryl ethers and 2-butynes catalyzed by the palladium(0)/PMe3 complex. Moreover, hydrogen migration was the rate-determining step for this channel. The dominant product was 2-methylidene-2H-chromenes P1, which is in agreement with experimental studies. PMID:25404544

  7. An Integrated Genomic Analysis of Aryl Hydrocarbon Receptor-Mediated Inhibition of B-Cell Differentiation

    OpenAIRE

    Abrew, K. Nadira; Kaminski, Norbert E.; Thomas, Russell S.

    2010-01-01

    The aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters differentiation of B cells and suppresses antibody production. A combination of whole-genome, microarray-based chromatin immunoprecipitation (ChIP-on-chip), and time course gene expression microarray analysis was performed on the mouse B-cell line CH12.LX following exposure to lipopolysaccharide (LPS) or LPS and TCDD to identify the primary and downstream transcriptional elements of B-cell differenti...

  8. Identification of Stanniocalcin 2 as a Novel Aryl Hydrocarbon Receptor Target Gene

    OpenAIRE

    Harper, Tod A.; Joshi, Aditya D.; Elferink, Cornelis J.

    2013-01-01

    Proper hepatocyte function is vital for survival; thus, unrepaired destruction of the parenchymal tissue leading to liver decompensation is devastating. Therefore, understanding the homeostatic process regulating liver regeneration is clinically important, and evidence that the aryl hydrocarbon receptor (AhR) can promote cell survival after intrinsic apoptotic stimuli is integral to the regenerative process. The current study uses primary hepatocytes to identify survival mechanisms consistent...

  9. Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions

    OpenAIRE

    Di meglio, Paola; Duarte, Joa?o h; Ahlfors, Helena; Owens, Nick d L.; Li, Ying; Villanova, Federica; Tosi, Isabella; Hirota, Keiji; Nestle, Frank o; Mrowietz, Ulrich; Gilchrist, Michael j; Stockinger, Brigitta

    2014-01-01

    Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanisms are largely unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists increased inflammation. Similarly, AhR signaling via the endogenous ligand FICZ reduced...

  10. A theoretical mechanistic investigation of asymmetric aziridination by N-Aryl-O-acylhydroxylamines.

    Science.gov (United States)

    Chaves, Humberto T.; Lobo, Ana M.; Prabhakar, Sundaresan; Rzepa, Henry S.

    1995-04-01

    This paper reports a theoretical investigation of the most probable mechanism for the asymmetric aziridination of olefins by N-aryl-O-acylhydroxylamines. The transition states of two possible mechanisms (Scheme 2) were studied. The transition state for pathway 2 (oxaziridine as intermediate) has a lower energy of activation than the energy of the transition state for pathway 1. The anionic transition state of pathway 2 is more stable than the neutral transition state.

  11. Synthesis and monoamine transporter affinity of 3-aryl substituted trop-2-enes.

    Science.gov (United States)

    Krunic, Aleksej; Mariappan, S V Santhana; Reith, Marteen E A; Dunn, William J

    2005-12-15

    A series of new 3-aryl-tropanes have been synthesized, and their affinities and selectivities were evaluated for monoamine transporters. (1RS)-3-(Fluoren-2-yl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene exhibited the highest affinity for the human serotonin transporter (IC(50)=14.5nM). It is also 52-fold and 230-fold selective over human dopamine and norepinephrine transporters, respectively. PMID:16202585

  12. Podocyte Injury Caused by Indoxyl Sulfate, a Uremic Toxin and Aryl-Hydrocarbon Receptor Ligand

    OpenAIRE

    Ichii, Osamu; Otsuka-kanazawa, Saori; Nakamura, Teppei; Ueno, Masaaki; Kon, Yasuhiro; Chen, Weiping; Rosenberg, Avi Z.; Kopp, Jeffrey B.

    2014-01-01

    Indoxyl sulfate is a uremic toxin and a ligand of the aryl-hydrocarbon receptor (AhR), a transcriptional regulator. Elevated serum indoxyl sulfate levels may contribute to progressive kidney disease and associated vascular disease. We asked whether indoxyl sulfate injures podocytes in vivo and in vitro. Mice exposed to indoxyl sulfate for 8 w exhibited prominent tubulointerstitial lesions with vascular damage. Indoxyl sulfate-exposed mice with microalbuminuria showed ischemic changes, while m...

  13. CuO hollow nanosphere-catalyzed cross-coupling of aryl iodides with thiols

    OpenAIRE

    Woo, Hyunje; Mohan, Balaji; Heo, Eunjung; Park, Ji Chan; Song, Hyunjoon; Park, Kang Hyun

    2013-01-01

    New functionalized CuO hollow nanospheres on acetylene black (CuO/AB) and on charcoal (CuO/C) have been found to be effective catalysts for C-S bond formation under microwave irradiation. CuO catalysts showed high catalytic activity with a wide variety of substituents which include electron-rich and electron-poor aryl iodides with thiophenols by the addition of two equivalents of K2CO3 as base in the absence of ligands.

  14. Tandem oxidation/halogenation of aryl allylic alcohols under Moffatt-Swern conditions.

    Science.gov (United States)

    Yin, Jiandong; Gallis, Christina E; Chisholm, John D

    2007-08-31

    Aryl allylic alcohols are converted to halogenated unsaturated ketones or allylic halides using excess Moffatt-Swern reagent. Electron-poor aromatic rings favor formation of the halogenated ketone, while electron-donating substituents in the ortho or para positions favor formation of the allylic halide. The oxidation/halogenation reaction performs well with both oxalyl chloride and oxalyl bromide, providing access to the corresponding chlorides or bromides, respectively. PMID:17685577

  15. Microwave-Assisted Cyanation of an Aryl Bromide Directly on a Metal-Organic Framework

    OpenAIRE

    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.

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

    OpenAIRE

    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 ?,...

  17. Omeprazole Attenuates Hyperoxic Injury in H441 Cells via Aryl hydrocarbon Receptor

    OpenAIRE

    Shivanna, Binoy; Chu, Chun; Welty, Stephen E.; Jiang, Weiwu; Wang, Lihua; Moorthy, Bhagavatula

    2011-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia in premature infants. Earlier we observed that aryl hydrocarbon receptor (AhR)-deficient mice are more susceptible to hyperoxic lung injury than AhR-sufficient mice, and this phenomenon was associated with a lack of expression of cytochrome P450 1A enzymes. Omeprazole, a proton pump inhibitor, used in humans with gastric acid related disorders, activates AhR in hepatocytes in vitro. However, the effects of omeprazole on Ah...

  18. Functional Deficiency of Aryl Hydrocarbon Receptor Augments Oxygen Toxicity-Induced Alveolar Simplification in Newborn Mice

    OpenAIRE

    Shivanna, Binoy; Zhang, Wenyan; Jiang, Weiwu; Welty, Stephen E.; Couroucli, Xanthi I.; Wang, Lihua; Moorthy, Bhagavatula

    2013-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. New BPD is characterized as having alveolar simplification. We reported previously that aryl hydrocarbon receptor (AhR) deficiency increased susceptibility to hyperoxic lung injury in adult mice, and this was associated with decreased expression of cytochrome P450 1A enzymes and increased lung inflammation. Whether AhR protects newborn mice against hyperoxia-induced alveolar simplification is un...

  19. Merging photoredox with nickel catalysis: Coupling of ?-carboxyl sp3-carbons with aryl halides

    OpenAIRE

    Zuo, Zhiwei; Ahneman, Derek T.; Chu, Lingling; Terrett, Jack A.; Doyle, Abigail G.; Macmillan, David W. C.

    2014-01-01

    Over the past 40 years, transition metal catalysis has enabled bond formation between aryl and olefinic (sp2) carbons in a selective and predictable manner with high functional group tolerance. Couplings involving alkyl (sp3) carbons have proven more challenging. Here, we demonstrate that the synergistic combination of photoredox catalysis and nickel catalysis provides an alternative cross-coupling paradigm, in which simple and readily available organic molecules can be systematically used as...

  20. Nickel-Catalyzed Regiodivergent Opening of Epoxides with Aryl Halides: Co-Catalysis Controls Regioselectivity

    OpenAIRE

    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...

  1. Nickel-catalyzed arylation, alkenylation, and alkynylation of unprotected thioglycosides at room temperature.

    Science.gov (United States)

    Brachet, Etienne; Brion, Jean-Daniel; Alami, Mouad; Messaoudi, Samir

    2013-11-01

    Unprotected thioglycosides were effective nucleophiles for Ni(0)-catalyzed C-S bond-forming reaction with functionalized (hetero)aryl, alkenyl, and alkynyl halides. The functional-group tolerance on the electrophilic partner was typically high and the anomeric selectivities of the thioglycosides were high in all cases. The efficiency of this general procedure was well-demonstrated by the synthesis of 4-methyl-7-thioumbelliferyl-?-D-cellobioside (MUS-CB). PMID:24108443

  2. Stereospecific pd-catalyzed cross-coupling reactions of secondary alkylboron nucleophiles and aryl chlorides.

    Science.gov (United States)

    Li, Ling; Zhao, Shibin; Joshi-Pangu, Amruta; Diane, Mohamed; Biscoe, Mark R

    2014-10-01

    We report the development of a Pd-catalyzed process for the stereospecific cross-coupling of unactivated secondary alkylboron nucleophiles and aryl chlorides. This process tolerates the use of secondary alkylboronic acids and secondary alkyltrifluoroborates and occurs without significant isomerization of the alkyl nucelophile. Optically active secondary alkyltrifluoroborate reagents undergo cross-coupling reactions with stereospecific inversion of configuration using this method. PMID:25226092

  3. Bitumen compounds

    Energy Technology Data Exchange (ETDEWEB)

    Koga, K.

    1981-11-19

    Bitumen compounds (BK) are patented which are for road pavements with high mechanical strength, produced through mixing the side products from the production of ferrosilicium (PPF), residues from the production of acetylene (OPA) from calcium carbide with a bitumen mixture, which includes bitumen (Bm) and a filler (Np). The bitumen composition includes 3 to 8 percent directly distilled bitumen or oxidized bitumen, 85 to 93.5 percent of a first filler (sand, roasted china clay or pearlite), 0.1 to 10 percent of a second filler (finely dispersed bank sand, clay, calcium carbonate, talc), 0.1 to 10 percent of the byproducts of the production of ferrosilicium (which contains uncrystallized anhydride of silica gel with a particle diameter of 0.1 micrometes) and residues from the production of acetylene). The ratio of the byproducts from the production of ferrosilicium to the residues of acetylene production is 1 to 9 to 9 to 1.

  4. Bismaleimide compounds

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Johnnie E. (Grandview, MO); Jamieson, Donald R. (Merriam, KS)

    1986-01-14

    Bismaleimides of the formula ##STR1## wherein R.sub.1 and R.sub.2 each independently is H, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, C1 or Br, or R.sub.1 and R.sub.2 together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R.sub.1 and R.sub.2 are not t-butyl or t-butoxy; X is O, S or Se; n is 1-3; and the alkylene bridging group, optionally, is substituted by 1-3 methyl groups or by fluorine, form polybismaleimide resins which have valuable physical properties. Uniquely, these compounds permit extended cure times, i.e., they remain fluid for a time sufficient to permit the formation of a homogeneous melt prior to curing.

  5. Bismaleimide compounds

    Energy Technology Data Exchange (ETDEWEB)

    Adams, J.E.; Jamieson, D.R.

    1986-01-14

    Bismaleimides of the formula shown in the diagram wherein R[sub 1] and R[sub 2] each independently is H, C[sub 1-4]-alkyl, C[sub 1-4]-alkoxy, Cl or Br, or R[sub 1] and R[sub 2] together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R[sub 1] and R[sub 2] are not t-butyl or t-butoxy; X is O, S or Se; n is 1--3; and the alkylene bridging group, optionally, is substituted by 1--3 methyl groups or by fluorine, form polybismaleimide resins which have valuable physical properties. Uniquely, these compounds permit extended cure times, i.e., they remain fluid for a time sufficient to permit the formation of a homogeneous melt prior to curing.

  6. Structural and biochemical impact of C8-aryl-guanine adducts within the NarI recognition DNA sequence: influence of aryl ring size on targeted and semi-targeted mutagenicity.

    Science.gov (United States)

    Sproviero, Michael; Verwey, Anne M R; Rankin, Katherine M; Witham, Aaron A; Soldatov, Dmitriy V; Manderville, Richard A; Fekry, Mostafa I; Sturla, Shana J; Sharma, Purshotam; Wetmore, Stacey D

    2014-12-01

    Chemical mutagens with an aromatic ring system may be enzymatically transformed to afford aryl radical species that preferentially react at the C8-site of 2'-deoxyguanosine (dG). The resulting carbon-linked C8-aryl-dG adduct possesses altered biophysical and genetic coding properties compared to the precursor nucleoside. Described herein are structural and in vitro mutagenicity studies of a series of fluorescent C8-aryl-dG analogues that differ in aryl ring size and are representative of authentic DNA adducts. These structural mimics have been inserted into a hotspot sequence for frameshift mutations, namely, the reiterated G3-position of the NarI sequence within 12mer (NarI(12)) and 22mer (NarI(22)) oligonucleotides. In the NarI(12) duplexes, the C8-aryl-dG adducts display a preference for adopting an anti-conformation opposite C, despite the strong syn preference of the free nucleoside. Using the NarI(22) sequence as a template for DNA synthesis in vitro, mutagenicity of the C8-aryl-dG adducts was assayed with representative high-fidelity replicative versus lesion bypass Y-family DNA polymerases, namely, Escherichia coli pol I Klenow fragment exo(-) (Kf(-)) and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Our experiments provide a basis for a model involving a two-base slippage and subsequent realignment process to relate the miscoding properties of C-linked C8-aryl-dG adducts with their chemical structures. PMID:25361967

  7. Synthesis and thermal degradation characterization of novel poly(phosphazene-aryl amides

    Directory of Open Access Journals (Sweden)

    Z. P. Zhao

    2012-04-01

    Full Text Available New fully aromatic poly(phosphazene-aryl amides were prepared by polycondensation reaction of our synthesized aromatic diamine: 1,1,3,5-tetraphenoxy-4,6-bis(4-aminophenoxyoligocyclotriphosphazene (monomer 1 with terephthaloyl dichloride. Their chemical structure and composition were characterized by elemental analysis, 1H and 31P NMR (Nuclear Magnetic Resonance, and FT-IR (Fourier transform infrared spectroscopy, whereas their thermal degradation properties were determined by DSC (Differential Scanning Calorimetry and TGA (Thermal Gravimertic Analysis techniques. The solid residues of all samples were analysed by FT-IR and SEM (Scanning Electron Microscopy. Compared to conventional PPTA (poly(p-phenylene terephthamide, PPAA (poly(phosphazene-aryl amide shows excellent thermal stability and solubility in polar protic solvents. All poly(phosphazene-aryl amides show two thermal degradation in the temperature range 150–600°C. The monomer 1, due to its structure, shows the first maximum rate of thermal decomposition temperature around 150–350°C, which may be due to the decomposition of the P–O–C bone. Morphology of the solid residues by Scanning Electron Microscope exhibit that the granular of the solid residues gradual disappearance with the increase of monomer 1 content. The surface layer of PPAA solid residues has been grumous, for the syneresis of P–O–P took place.

  8. 4-Aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles: multitasking skeleton as a self-assembling unit.

    Science.gov (United States)

    Pastor, M Jesús; Torres, Iván; Cebrián, Cristina; Carrillo, José Ramón; Díaz-Ortiz, Ángel; Matesanz, Emilio; Buendía, Julia; García, Fátima; Barberá, Joaquín; Prieto, Pilar; Sánchez, Luis

    2015-01-19

    The synthesis of a series of 4-aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles derivatives is reported and the influence exerted by peripheral substitution on the morphology of the aggregates generated from these 1,2,4-triazoles is investigated by SEM imaging. The presence of paraffinic side chains results in long fibrillar supramolecular structures, but unsubstituted triazoles self-assemble into thinner ribbons and needle-like aggregates. The crystals obtained from methoxy-substituted triazoles have been utilised to elaborate a model that helps to justify aggregation of the investigated 1,2,4-triazoles, in which the operation of arrays of C-H???? non-covalent interactions plays a significant role. The results presented herein demonstrate the ability of simple molecules to behave as multitasking scaffolds with different properties, depending on peripheral substitution. Thus, although 1,2,4-triazoles without long paraffinic side chains exhibit optical waveguiding behaviour, triazoles endowed with peripheral paraffinic side chains exhibit hexagonal columnar mesomorphism. PMID:25413614

  9. Photosensitized oxidation of aryl benzyl sulfoxides. Evidence for nucleophilic assistance to the C-s bond cleavage of aryl benzyl sulfoxide radical cations.

    Science.gov (United States)

    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

  10. 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

    Directory of Open Access Journals (Sweden)

    El?bieta Szaco?

    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.

  11. 1,2-Dimethylimidazole-4-sulfonyl Chloride, a Novel Derivatization Reagent for the Analysis of Phenolic Compounds by Liquid Chromatography Electrospray Tandem Mass Spectrometry: Application to 1-Hydroxypyrene in Human Urine

    OpenAIRE

    Xu, Li; Spink, David C.

    2007-01-01

    A novel derivatization method employing 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC) to improve the mass spectrometric response for phenolic compounds in liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) and tandem mass spectrometry (LC-ESI-MS/MS) is described. Several environmentally relevant compounds, including chloro-, aryl- and alkylphenols, steroidal estrogens, and hydroxy-polycyclic aromatic hydrocarbons (OHPAHs), were selected to evaluate this technique....

  12. Analysis of aryl hydrocarbon receptor ligands in kraft mill effluents by a combination of yeast bioassays and CG-MS chemical determinations.

    Science.gov (United States)

    Chamorro, Soledad; Monsalvez, Elizabeth; Piña, Benjamín; Olivares, Alba; Hernández, Víctor; Becerra, José; Vidal, Gladys

    2013-01-01

    Aryl Hydrocarbon Receptor (AhR) ligands also known as dioxin-like compounds, constitute a substantial part of the total toxicity from many pollution sources, including pulp mill effluents. The aim of this article was to evaluate dioxin-like activity in different kraft mill effluents by a combination of yeast bioassays and gas chromatography-mass spectrometry (GC-MS) chemical analysis. The study includes kraft mill effluents from three sources of raw material: Pinus radiata, Eucalyptus globulus and a combination of both (50% each). The Recombinant Yeast Assay (RYA) showed an effective concentration of AhR ligands more than 30-fold higher in Eucalyptus globulus than in Pinus radiata effluents. Our results suggest that specific ligands, rather than the total amount of extractive material, determined the observed activity. Analysis of extract composition by GC-MS indicated that moderately hydrophobic aromatic compounds were likely responsible for the observed dioxin-like activity. In particular, benzaldehyde derivatives appeared as candidates for eliciting the observed dioxin-like activity in pulp mill effluents, giving their structural properties and their high concentration in AhR ligand-rich samples. PMID:23043335

  13. Mesomeric and twisted intramolecular-charge-transfer states as a key to polarity-dependent fluorescence of donor-acceptor-substituted aryl pyrenes

    International Nuclear Information System (INIS)

    Computational study by the AM1 method has been performed for pyrene-based donor-acceptor-substituted systems, with the aim to elucidate the origin of their polarity-dependent fluorescence governed by mesomeric and twisted internal-charge-transfer (MICT and TICT, resp.) states. Using theoretical methods, principal relationships have been established between the constitution of arylpyrene derivatives (donor-acceptor strength of substituents, the substitution pattern, sterical hindrance, inclusion of additional aryl spacers between the donor and acceptor moieties, etc.) and environmental effects (solvent polarity and external electric field strength), and the properties of the MICT and TICT states (energy, localization, dipole moment, allowedness). These relationships have been compared to the experimental fluorescence properties. The substituent-induced donor-acceptor difference has been varied in a continuous way in both directions by employing point charges in the molecular surrounding ('sparkles'). A remarkable feature of the phenylpyrene molecule has thus been revealed: it can exist in two MICT and two TICT states, the CT states in each pair being oppositely polarized and much the same in energy. It is shown, moreover, that the quantum-chemically calculated trends in MICT and TICT energies in the families of related compounds can be qualitatively judged from simple MO considerations including the analysis of frontier MO energies and shapes for the isolated moleculargies and shapes for the isolated molecular subunits. The approach employed is, therefore, applicable as a first-step tool in the design of compounds with the desired features of polarity-sensitive fluorescence

  14. Toxicity of aryl- and benzylhalides to Daphnia magna and classification of their mode of action based on quantitative structure-activity relationship

    Energy Technology Data Exchange (ETDEWEB)

    Marchini, S.; Passerini, L.; Hoglund, M.D.; Pino, A.; Nendza, M.

    1999-12-01

    The acute toxicity of aryl- and benzylhalides to Daphnia magna was investigated to test the validity of existing classification schemes for chemicals by mode of action, mainly based on fish studies, and the applicability of predictive quantitative structure-activity relationship (QSAR) models. Halobenzenes and halotoluenes are generally agreed to be unambiguous baseline toxicants (class 1) with the major exception of the benzylic structures, which are reactive in fish tests (class 3). Eighty-nine percent of the arylhalides tested in this study match a log P{sub ow}-dependent QSAR, including fluorinated, chlorinated, brominated, and iodinated derivatives, thereby confirming the validity of the baseline models also for variously halogenated compounds (other than only-chloro compounds). The toxicities of the benzylhalides relative to baseline QSARs clearly indicate that these compounds belong to two classes of mode of action, i.e., they either act as narcotic toxicants (class 1) or reveal excess toxicity due to unspecific reactivity (class 3). On some occasions, the assignment to the two classes of F. magna deviates from the structural rules derived from fish, i.e., iodinated compounds as well as {alpha},{alpha}-Cl{sub 2}-toluene's lack reactive excess toxicity but behave as nonpolar nonspecific toxicants. The QSARs derived during this study reveal lower slopes and higher intercepts than typical baseline models and, together with the analysis of mixture toxicity studies, behavioral studies, and critical body burden, advocate the hypothesis that there are several different ways to produce baseline toxicity. Most halobenzenes and halotoluenes are actually baseline chemicals with some extra reactivity and as such form a subgroup, whose limits still have to be defined. Different primary sites of action could explain why the chemicals are discriminated by different classification systems, but still they must have some rate-limiting interaction in common as they fit the same log P{sub ow}-dependent baseline QSAR.

  15. Synthesis, urease inhibition, antioxidant and antibacterial studies of some 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones and their 3,6-disubstituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Hanif, Muhammad; Saleem, Muhammad; Rama, Nasim Hasan, E-mail: nhrama@qau.edu.pk, E-mail: drjamshed@ciit.net.pk [Department of Chemistry, Quaid-i-Azam University, Islamabad (Pakistan); Hussain, Muhammad Tahir [Department of Applied Sciences, National Textile University, Faisalabad (Pakistan); Zaib, Sumera; Aslam, Muhammad Adil M.; Iqbal, Jamshed [Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad (Pakistan); Jones, Peter G. [Institute for Inorganic and Analytical Chemistry, Technical University of Braunschweig, Braunschweig (Germany)

    2012-05-15

    A new series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones, bearing various methoxybenzyl- and methoxyphenethyl groups, was synthesized by refluxing potassium hydrazinecarbodithioate salts in dilute aqueous solution of hydrazine hydrate. These salts were formed by the reaction of acid hydrazides and carbon disulfide in methanolic potassium hydroxide solution at 0-5 deg C. 4-Amino- 5-aryl-3H-1,2,4-triazole-3-thiones were condensed with different substituted aromatic acids to yield 3,6-disubstituted-1,2,4-triazolo[3,4-b]1,3,4-thiadiazoles. The structures of the synthesized compounds were characterized by infrared (IR), {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR), elemental analysis and mass spectrometric (MS) studies. All the synthesized compounds were screened for their urease inhibition, antioxidant and antibacterial activities. Some compounds showed excellent urease inhibition activity, more than the standard drug. Others exhibited potent antioxidant activity. All the compounds showed significant antibacterial activities as compared to the standard drug. (author)

  16. Stereoselective synthesis and physicochemical properties of liquid-crystal compounds possessing a trans-2,5-disubstituted tetrahydropyran ring with negative dielectric anisotropy.

    Science.gov (United States)

    Araki, Keisuke; Yamamoto, Tetsuya; Tanaka, Ryoji; Tanaka, Saori; Ushioda, Makoto; Gotoh, Yasuyuki; Yamakawa, Tetsu; Inoue, Munenori

    2015-02-01

    Three stereoselective syntheses and the physicochemical properties of trans,trans-5-(4-ethoxy-2,3-difluorophenyl)-2-(4-propylcyclohexyl)tetrahydropyran, which is an important liquid-crystal compound with a large negative dielectric anisotropy (??=-7.3), are described. The key step in the construction of the trans-2,5-disubstituted tetrahydropyran ring in the first approach involved a benzylic cation mediated intramolecular olefin cyclization of a 2-allyloxy-1-arylethanol derivative. The second method included the Et2 Zn-induced 1,2-aryl shift of a bromohydrin obtained from a hetero-Diels-Alder reaction, followed by stereoselective bromination. The third approach utilized the hetero-Diels-Alder reaction of trans-4-propylcyclohexanecarboxaldehyde and a 2-aryl-3-(trimethylsilyl)oxy-1,3-butadiene, followed by stereoselective protonation. From results obtained by using a quantum chemical calculation method, the reason why the target compound shows a large negative ?? value is discussed. PMID:25504103

  17. Easy entry into reduced Ar-BIANH2 compounds: a new class of quinone/hydroquinone-type redox-active couples with an easily tunable potential.

    Science.gov (United States)

    Viganò, Marta; Ferretti, Francesco; Caselli, Alessandro; Ragaini, Fabio; Rossi, Manuela; Mussini, Patrizia; Macchi, Piero

    2014-10-27

    Ar-BIANH2 bearing different substituents on the aryl rings have been synthesized in high yield by reduction of the corresponding bis(aryl)acenaphthenequinonediimine (Ar-BIAN) compounds. The structure of p-CH3 C6 H4 -BIANH2 in the solid state was determined by X-ray diffraction. An exhaustive voltammetric investigation of the two parallel BIAN and BIANH2 series afforded a first rationalization of the redox properties of these molecules, highlighting their analogies with quinone/hydroquinone systems. Such analogies, in combination with the much more negative reduction potential range of Ar-BIAN compounds with respect to quinones, can afford to extend the range of reduction potentials so far obtainable by the use of quinones. PMID:25214241

  18. N-(1-Oxy-2-picolyl)oxalamic acids as a new type of O,O-ligands for the Cu-catalyzed N-arylation of azoles with aryl halides in water or organic solvent.

    Science.gov (United States)

    Wang, Yongbin; Zhang, Yu; Yang, Beibei; Zhang, Ao; Yao, Qizheng

    2015-03-18

    N-(1-Oxy-pyridin-2-ylmethyl)oxalamic acids () were identified as novel efficient ligands for copper-catalyzed C-N cross-coupling of azoles and aryl halides in water. The N-arylation of imidazoles, indoles and pyrazoles proceeded with moderate to excellent yields and complete selectivity over aromatic amines and phenols. Moreover, , which is also efficient in organic solvent with low catalyst loading, can be used to promote the N-arylation reactions with water-sensitive materials. The catalytic mechanism was proposed based on the results of several verification experiments which indicated that the ligands as new-type chelators may coordinate to Cu(i) with two oxygen atoms of N-oxide and amide in the coupling process. PMID:25740426

  19. One-pot four-component synthesis of 2-aryl-3,3-dihaloacrylonitriles using potassium hexacyanoferrate(II) as environmentally benign cyanide source

    International Nuclear Information System (INIS)

    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)

  20. Metal-free tandem oxidative aryl migration and C-C bond cleavage: synthesis of ?-ketoamides and esters from acrylic derivatives.

    Science.gov (United States)

    Liu, Le; Du, Liang; Zhang-Negrerie, Daisy; Du, Yunfei; Zhao, Kang

    2014-11-01

    A novel tandem metal-free oxidative aryl migration/C-C bond-cleavage reaction, mediated by hypervalent iodine reagent, has been discovered. The presented transformation provided straightforward access to important ?-ketoamide and ?-ketoester derivatives from readily available acrylic derivatives via a concerted process of 1,2-aryl shift concomitant with C-C bond cleavage. PMID:25343425

  1. Control of oxophilicity of cerium (IV) ammonium nitrate by addition of hydrogen peroxide. A novel preparation of 3-aroyl-2-aryl-4H-1-benzopyran-4-ones

    International Nuclear Information System (INIS)

    Oxophilicity of cerium(IV) ammonium nitrate (CAN) can be controlled by addition of hydrogen peroxide and such a control has been utilized to prepare 3-aroyl-2-aryl-4H-1-benzopyran-4-ones 2a-d from 3-arylidene-2-aryl-2,3-dihydro-4H-1-benzopyran-4-ones 1a-d in good yields

  2. Synthesis of 2,3-epoxy-1-phenyl-3-aryl-1-propanone by combination of phase transfer catalyst and ultrasound irradiation

    Directory of Open Access Journals (Sweden)

    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.

  3. Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3? (GSK-3?) phosphorylation inhibitors.

    Science.gov (United States)

    Zhao, Ping; Li, Yanzhong; Gao, Guangwei; Wang, Shuai; Yan, Yun; Zhan, Xiaoping; Liu, Zenglu; Mao, Zhenmin; Chen, Shaoxiong; Wang, Liqun

    2014-10-30

    A series of N-alkyl or aryl substituted isoindigo derivatives have been synthesized and their anti-proliferative activity was evaluated by Sulforhodamine B (SRB) assay. Some of the target compounds exhibited significant antitumor activity, including compounds 6h and 6k (against K562 cells), 6i (against HeLa cells) and 6j (against A549 cells). N-(p-methoxy-phenyl)-isoindigo (6k) exhibited a high and selective anti-proliferative activity against K562 cells (IC50 7.8 ?M) and induced the apoptosis of K562 cells in a dose-dependent manner. Compound 6k arrested the cell cycle at S phase in K562 cells by decreasing the expression of cyclin A and CDK2, which played critical roles in DNA replication and passage through G2 phase. Moreover, compound 6k down-regulated the expression of p-GSK-3? (Ser9), ?-catenin and c-myc proteins, up-regulated the expression of GSK-3?, consequently, suppressed Wnt/?-catenin signaling pathway and induced the apoptosis of K562 cells. The binding mode of compound 6k with GSK-3? was simulated using molecular docking tools. All of these studies gave a better understanding to the molecular mechanisms of this class of agents and clues to develop dual CDK2/GSK-3? (Ser9) phosphorylation inhibitors applied in cancer chemotherapy. PMID:25151579

  4. Electrosynthesis and structural characterization of a novel aryl ether trimer

    Energy Technology Data Exchange (ETDEWEB)

    Besbes-Hentati, Salma [Laboratoire de Thermodynamique et d' Electrochimie, Departement de Chimie, Faculte des Sciences de Bizerte, Zarzouna 7021, Bizerte (Tunisia)]. E-mail: salma.hentati@fsb.rnu.tn; Said, Hechmi [Laboratoire de Thermodynamique et d' Electrochimie, Departement de Chimie, Faculte des Sciences de Bizerte, Zarzouna 7021, Bizerte (Tunisia); Bouvet, Marcel [Laboratoire de Chimie Inorganique et Materiaux Moleculaires, CNRS-UMR 7071, Universite Pierre et Marie Curie-Paris 6, 4 Place Jussieu, 75252 Paris Cedex 05 (France)

    2007-04-01

    The structure of a novel trimer formed by three p-tert-butyl anisole moieties via the controlled potential electrolysis of p-tert-butyl anisole was determined by X-ray diffraction method. By cyclic voltammetry, we report a multistep electron transfer, each followed by a chemical reaction, resulting in an ECECEC mechanism. Preparative scale oxidation of p-tert-butyl anisole in dry acetonitrile leads to its two first oligomers. The symmetrical dimer, 2,2'-dimethoxy-5,5'-di-tert-butylbiphenyl, shows that the favored coupling sites are those in the ortho position of the methoxy group. The title compound, namely the 1-methoxy-bis-2,3-(2'-methoxy-5'-tert-butylphenyl)-4-tert-butylbenzene crystallizes in triclinic space group P-1 with a = 10.571(3) A, b = 11.739(1) A, c = 12.733(2) A, {alpha} = 74.64(1){sup o}, {beta} = 88.71(2){sup o}, {gamma} 76.58(2){sup o}, V = 1480.8(5) A{sup 3}, and Z = 2. The structural analysis reveals that two p-tert-butyl anisole moieties are linked in ortho position on a third p-tert-butyl anisole fragment.

  5. Electrosynthesis and structural characterization of a novel aryl ether trimer

    International Nuclear Information System (INIS)

    The structure of a novel trimer formed by three p-tert-butyl anisole moieties via the controlled potential electrolysis of p-tert-butyl anisole was determined by X-ray diffraction method. By cyclic voltammetry, we report a multistep electron transfer, each followed by a chemical reaction, resulting in an ECECEC mechanism. Preparative scale oxidation of p-tert-butyl anisole in dry acetonitrile leads to its two first oligomers. The symmetrical dimer, 2,2'-dimethoxy-5,5'-di-tert-butylbiphenyl, shows that the favored coupling sites are those in the ortho position of the methoxy group. The title compound, namely the 1-methoxy-bis-2,3-(2'-methoxy-5'-tert-butylphenyl)-4-tert-butylbenzene crystallizes in triclinic space group P-1 with a = 10.571(3) A, b = 11.739(1) A, c = 12.733(2) A, ? = 74.64(1)o, ? = 88.71(2)o, ? 76.58(2)o, V = 1480.8(5) A3, and Z = 2. The structural analysis reveals that two p-tert-butyl anisole moieties are linked in ortho position on a third p-tert-butyl anisole fragment

  6. Synthesis of New Bioactive Sulfur Compounds Bearing Heterocyclic Moiety and Their Analytical Applications

    Directory of Open Access Journals (Sweden)

    Mohammad. S. T. Makki

    2011-01-01

    Full Text Available Some new bioactive sulfur compounds bearing heterocyclic nitrogen moieties such as 3- imino–2-thioxo-4,5-dihydro- thiazolidin – 4-one (3, 3-imino – 2-thioxo -3,4,5,6-tetrahydro-1, 3-thiazine-4, 6- (2 Hdione(4, N- substituted – pyrazol -3,5-dione (10 , 1,3 –disubstituted -2-thioxo-pyrimidin-4,6 –dione (11 and di –(3,5-diaminopyrazolin-1-ylthioketone (13 derived from dithioc formic acid hydrazide (1 and thiocarbohydrazide (7were prepared via condensation of compound 1 or 7 with acyclic and cyclic oxo compounds (e.g. aldehydes andketones in 1:1 and 1:2 molar ratios, and addition of iso thiocyanate or treatment with active methylene compoundsfollowed by ring closing reactions in different media (Schemes I & II. The biocidal effect of some compoundstowards some bacteria and fungi was evaluated. Compound 4 was used as selective chelating agent forspectrophotometric determination of mercury (II ions. The limit of detection (LOD and quantification (LOQ ofthe developed spectrophotometric method were found to be equal to 0.16 and 0.52 ?g mL-1 mercury (II,respectively. Compound 4 was also physically immobilized onto polyurethane foam (PUFs and was successfullyused as solid sorbent in packed column for removal of mercury (II ions from wastewater.

  7. Synthesis of [.sup.13C] and [.sup.2H] substituted methacrylic acid, [.sup.13C] and [.sup.2H] substituted methyl methacrylate and/or related compounds

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, Marc A. (Santa Fe, NM); Martinez, Rodolfo A. (Santa Fe, NM); Unkefer, Clifford J. (Los Alamos, NM)

    2008-01-22

    The present invention is directed to labeled compounds of the formulae ##STR00001## wherein Q is selected from the group consisting of --S--, --S(.dbd.O)--, and --S(.dbd.O).sub.2--, Z is selected from the group consisting of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure ##STR00002## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently selected from the group consisting of hydrogen, a C.sub.1-C.sub.4 lower alkyl, a halogen, and an amino group selected from the group consisting of NH.sub.2, NHR and NRR' where R and R' are each independently selected from the group consisting of a C.sub.1-C.sub.4 lower alkyl, an aryl, and an alkoxy group, and X is selected from the group consisting of hydrogen, a C.sub.1-C.sub.4 lower alkyl group, and a fully-deuterated C.sub.1-C.sub.4 lower alkyl group. The present invention is also directed to a process of preparing labeled compounds, e.g., process of preparing [.sup.13C]methacrylic acid by reacting a (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13CH.sub.2)-- aryl sulfone precursor with .sup.13CHI to form a (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13C(.sup.13CH.sub.3).sub.2)-- aryl sulfone intermediate, and, reacting the (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13C(.sup.13CH.sub.3).sub.2)-- aryl sulfone intermediate with sodium hydroxide, followed by acid to form [.sup.13C]methacrylic acid. The present invention is further directed to a process of preparing [.sup.2H.sub.8]methyl methacrylate by reacting a (HOOC--C(C.sup.2H.sub.3).sub.2-- aryl sulfinyl intermediate with CD.sub.3I to form a (.sup.2H.sub.3COOC--C(C.sup.2H.sub.3).sub.2)-- aryl sulfinyl intermediate, and heating the(.sup.2H.sub.3COOC--C(C.sup.2H.sub.3).sub.2)-- aryl sulfinyl intermediate at temperatures and for time sufficient to form [.sup.2H.sub.8]methyl methacrylate.

  8. Synthesis of [.sup.13C] and [.sup.2H] substituted methacrylic acid, [.sup.13C] and [.sup.2H] substituted methyl methacrylate and/or related compounds

    Science.gov (United States)

    Alvarez, Marc A. (Santa Fe, NM); Martinez, Rodolfo A. (Santa Fe, NM); Unkefer, Clifford J. (Los Alamos, NM)

    2008-01-22

    The present invention is directed to labeled compounds of the formulae ##STR00001## wherein Q is selected from the group consisting of --S--, --S(.dbd.O)--, and --S(.dbd.O).sub.2--, Z is selected from the group consisting of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure ##STR00002## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently selected from the group consisting of hydrogen, a C.sub.1-C.sub.4 lower alkyl, a halogen, and an amino group selected from the group consisting of NH.sub.2, NHR and NRR' where R and R' are each independently selected from the group consisting of a C.sub.1-C.sub.4 lower alkyl, an aryl, and an alkoxy group, and X is selected from the group consisting of hydrogen, a C.sub.1-C.sub.4 lower alkyl group, and a fully-deuterated C.sub.1-C.sub.4 lower alkyl group. The present invention is also directed to a process of preparing labeled compounds, e.g., process of preparing [.sup.13C]methacrylic acid by reacting a (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13CH.sub.2)-- aryl sulfone precursor with .sup.13CHI to form a (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13C(.sup.13CH.sub.3).sub.2)-- aryl sulfone intermediate, and, reacting the (CH.sub.3CH.sub.2O--.sup.13C(O)--.sup.13C(.sup.13CH.sub.3).sub.2)-- aryl sulfone intermediate with sodium hydroxide, followed by acid to form [.sup.13C]methacrylic acid. The present invention is further directed to a process of preparing [.sup.2H.sub.8]methyl methacrylate by reacting a (HOOC--C(C.sup.2H.sub.3).sub.2-- aryl sulfinyl intermediate with CD.sub.3I to form a (.sup.2H.sub.3COOC--C(C.sup.2H.sub.3).sub.2)-- aryl sulfinyl intermediate, and heating the(.sup.2H.sub.3COOC--C(C.sup.2H.sub.3).sub.2)-- aryl sulfinyl intermediate at temperatures and for time sufficient to form [.sup.2H.sub.8]methyl methacrylate.

  9. 3-Arylisoxazolyl-5-carboxylic acid and 5-(Hydroxymethyl)-3-aryl-2-isoxazoline as molecular platforms for liquid-crystalline materials

    Scientific Electronic Library Online (English)

    Aline, Tavares; Paolo R., Livotto; Paulo F. B., Gonçalves; Aloir A., Merlo.

    1742-17-01

    Full Text Available A síntese de uma plataforma molecular para materiais líquido-cristalinos derivados do ácido 3-arilisoxazolil-5-carboxílico (1) e do 5-(hidroximetil)-3-aril-2-isoxazolina (2) é descrita. Os intermediários 1 e 2 são obtidos através da reação de cicloadição [3+2] 1,3-dipolar entre arilóxidos de nitrila [...] s e os dipolarófilos ácido acrílico e álcool alílico, respectivamente. Os compostos cristais líquidos são sintetizados através de uma estratégia de alongamento molecular do núcleo primitivo isoxazolínico pela conexão de subunidades arilacetilênicas, as quais foram obtidas da reação de Sonogashira. Sob essas condições, séries de cristais líquidos 5a-c, 6, 7a-g e 8a-d têm sido sintetizadas com rendimentos de médios para bons. Os compostos finais apresentam propriedades líquido-cristalinas nematogênica e esmectogênica. Um cálculo DFT no nível B3LYP/6-31G(d,p) é também apresentado e alguns parâmetros estruturais obtidos são 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.

  10. Palladium(II)-Catalyzed Sequential C-H Arylation/Aerobic Oxidative C-H Amination: One-Pot Synthesis of Benzimidazole-Fused Phenanthridines from 2-Arylbenzimidazoles and Aryl Halides.

    Science.gov (United States)

    Zhao, Gongyuan; Chen, Chunxia; Yue, Yixia; Yu, Yanhan; Peng, Jinsong

    2015-03-01

    Starting from 2-arylbenzimidazoles and aryl halides, an efficient palladium-based catalytic method for the synthesis of benzimidazole-fused phenanthridines has been developed. This reaction sequence comprises intermolecular C-H arylation and intramolecular aerobic oxidative C-H amination, involving the rupture of two C-H bonds, one C-X bond, and one N-H bond in one pot. The Pd(II)-Pd(IV)-Pd(II) and Pd(II)-Pd(0)-Pd(II) catalytic cycles work together under the reported conditions to generate phenanthridines with diverse substituents. PMID:25658883

  11. Palladium-catalyzed carbonylative coupling of (2-azaaryl)methyl anion equivalents with (hetero)aryl bromides.

    Science.gov (United States)

    Jusseau, Xavier; Yin, Hongfei; Lindhardt, Anders T; Skrydstrup, Troels

    2014-11-24

    Conditions for the palladium-catalyzed coupling of (2-pyridyl)acetones with aryl bromides have been developed. Followed by an acid-promoted deacetylation step, the desired 1-(het)aryl-2-(2-pyridyl)ethanones were obtained in good to excellent yields with high functional group tolerance. Test reactions revealed that both the addition of MgCl2 and a specifically positioned heteroatom in the heteroaromatic ring were crucial for product formation indicating the importance of a chelated intermediate in the reaction mechanism. The reaction conditions proved suitable for a number of 5- and 6-membered heteroaromatic starting materials affording all products in good yields. The utility of the obtained 1-(het)aryl-2-(2-pyridyl)ethanones was demonstrated by the straightforward synthesis of several multiaromatic derivatives in only few additional steps. PMID:25302485

  12. Facile Access to Sterically Hindered Aryl Ketones via Carbonylative Cross-Coupling: Application to the Total Synthesis of Luteolin.

    Science.gov (United States)

    O'Keefe, B Michael; Simmons, Nicholas; Martin, Stephen F

    2011-06-17

    A general and mild protocol for achieving the carbonylative cross-coupling of sterically-hindered, ortho-disubstituted aryl ketones is reported. The commercially available PEPPSI-IPr catalyst is shown to efficiently promote the carbonylative cross-coupling of hindered ortho-disubstituted aryl iodides to give diaryl ketones; traditional phosphine catalysts are less effective. Carbonylative Suzuki-Miyaura cross-couplings provide a diverse array of biaryl ketones in good to excellent yields. The same catalyst is also shown to catalyze a carbonylative Negishi cross-coupling reaction, utilizing a variety of alkynyl zinc reagents to give the corresponding alkynyl aryl ketones. Application of this new methodology to the synthesis of the natural product luteolin is reported. PMID:21712966

  13. Picolinamides as effective ligands for copper-catalysed aryl ether formation: structure-activity relationships, substrate scope and mechanistic investigations.

    Science.gov (United States)

    Sambiagio, Carlo; Munday, Rachel H; Marsden, Stephen P; Blacker, A John; McGowan, Patrick C

    2014-12-22

    The use of picolinic acid amide derivatives as an effective family of bidentate ligands for copper-catalysed aryl ether synthesis is reported. A fluorine-substituted ligand gave good results in the synthesis of a wide range of aryl ethers. Even bulky phenols, known to be very challenging substrates, were shown to react with aryl iodides with excellent yields using these ligands. At the end of the reaction, the first examples of end-of-life Cu species were isolated and identified as Cu(II) complexes with several of the anionic ligands tested. A preliminary mechanistic investigation is reported that suggests that the substituents on the ligands might have a crucial role in determining the redox properties of the metal centre and, consequently, its efficacy in the coupling process. An understanding of these effects is important for the development of new efficient and tunable ligands for copper-based chemistry. PMID:25346139

  14. ?-selective C-arylation of silyl protected 1,6-anhydroglucose with arylalanes: the synthesis of SGLT2 inhibitors.

    Science.gov (United States)

    Henschke, Julian P; Wu, Ping-Yu; Lin, Chen-Wei; Chen, Shi-Feng; Chiang, Pei-Chen; Hsiao, Chi-Nung

    2015-02-20

    The stereoselective arylation of hydroxy protected 1,6-anhydro-?-d-glucose with arylalanes to provide ?-C-arylglucosides is reported. Modification of triarylalanes, Ar3Al, with strong Brønsted acids (HX) or AlCl3 produced more reactive arylating agents, Ar2AlX, while the incorporation of alkyl dummy ligands into the arylating agents was also viable. Me3Al and i-Bu2AlH were found useful in the in situ blocking of the C3-hydroxyl group of 2,4-di-O-TBDPS protected 1,6-anhydroglucose. The utility of the method was demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin. PMID:25629294

  15. Facile Access to Sterically Hindered Aryl Ketones via Carbonylative Cross-Coupling: Application to the Total Synthesis of Luteolin

    Science.gov (United States)

    O’Keefe, B. Michael; Simmons, Nicholas

    2011-01-01

    A general and mild protocol for achieving the carbonylative cross-coupling of sterically-hindered, ortho-disubstituted aryl ketones is reported. The commercially available PEPPSI-IPr catalyst is shown to efficiently promote the carbonylative cross-coupling of hindered ortho-disubstituted aryl iodides to give diaryl ketones; traditional phosphine catalysts are less effective. Carbonylative Suzuki-Miyaura cross-couplings provide a diverse array of biaryl ketones in good to excellent yields. The same catalyst is also shown to catalyze a carbonylative Negishi cross-coupling reaction, utilizing a variety of alkynyl zinc reagents to give the corresponding alkynyl aryl ketones. Application of this new methodology to the synthesis of the natural product luteolin is reported. PMID:21712966

  16. Design and stereoselective synthesis of a C-aryl furanoside as a conformationally constrained CHIR-090 analogue

    DEFF Research Database (Denmark)

    Oddo, Alberto; Holl, Ralph

    2012-01-01

    The UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) is a promising target for the development of novel antibiotic substances against multidrug-resistant Gram-negative bacteria. The C-aryl glycoside 3 was designed as conformationally constrained analogue of the potent LpxC-inhibitor CHIR-090. The chiral pool synthesis of 3 started with D-mannose. The C-aryl glycoside 8 was synthesized stereoselectively by nucleophilic attack of 4-iodine-substituted phenyllithium and subsequent reduction with Et(3)SiH. The ester 10 was obtained in a one-pot diol cleavage, CrO(3) oxidation, and esterification. A Sonogashira reaction of the aryl iodide 11 led to the alkyne 17 which was transformed with H(2)NOH into the hydroxamic acid 3.

  17. Recyclable heterogeneous copper oxide on alumina catalyzed coupling of phenols and alcohols with aryl halides under ligand-free conditions.

    Science.gov (United States)

    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. Determination of arylglycerol-beta-aryl ethers and other linkages in lignins using DFRC/(31)P NMR.

    Science.gov (United States)

    Tohmura, S; Argyropoulos, D S

    2001-02-01

    An analytical method for lignins has been developed that involves derivatization followed by reductive cleavage (DFRC), depolymerization, and quantitative (31)P NMR spectroscopy. This technique detects and quantifies the various ether linkages present in softwood residual kraft lignins (RKL) and milled wood lignins (MWL). In addition, the technique supplies new quantitative information about beta-aryl ethers linked to condensed and noncondensed aromatic moieties, including dibenzodioxocins. Within RKL, beta-aryl ether bonds connected to condensed phenolic moieties predominated over those connected to noncondensed phenolic moieties. In addition, the amount of DFRC monomers determined by gas chromatography was minute in the RKL but large in the MWL. This indicates that almost all noncondensed beta-aryl ether linkages were cleaved during kraft pulping. The method offers new avenues for the detailed investigation of the bonding patterns of native and technical lignins. PMID:11261988

  19. Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor.

    Science.gov (United States)

    McGee, Sean P; Konstantinov, Alex; Stapleton, Heather M; Volz, David C

    2013-05-01

    Firemaster 550 (FM550) is an additive flame retardant formulation of brominated and aryl phosphate ester (APE) components introduced as a major replacement product for the commercial polybrominated diphenyl ether mixture (known as PentaBDE) used primarily in polyurethane foam. However, little is known about the potential effects of FM550-based ingredients during early vertebrate development. Therefore, we first screened the developmental toxicity of each FM550 component using zebrafish as an animal model. Based on these initial screening assays, we found that exposure to the brominated components as high as 10µM resulted in no significant effects on embryonic survival or development, whereas exposure to triphenyl phosphate (TPP) or mono-substituted isopropylated triaryl phosphate (mono-ITP)-two APEs comprising almost 50% of FM550-resulted in targeted effects on cardiac looping and function during embryogenesis. As these cardiac abnormalities resembled aryl hydrocarbon receptor (AHR) agonist-induced phenotypes, we then exposed developing embryos to TPP or mono-ITP in the presence or absence of an AHR antagonist (CH223191) or AHR2-specific morpholino. Based on these studies, we found that CH223191 blocked heart malformations following exposure to mono-ITP but not TPP, whereas AHR2 knockdown failed to block the cardiotoxic effects of both components. Finally, using a cell-based human AHR reporter assay, we found that mono-ITP (but not TPP) exposure resulted in a significant increase in human AHR-driven luciferase activity at similar nominal concentrations as a potent reference AHR agonist (?-naphthoflavone). Overall, our findings suggest that two major APE components of FM550 induce severe cardiac abnormalities during early vertebrate development. PMID:23377616

  20. Pd-catalyzed Heck reactions of aryl bromides with 1,2-diarylethenes

    Scientific Electronic Library Online (English)

    Jones, Limberger; Silvia, Poersch; Adriano L, Monteiro.

    1389-13-01

    Full Text Available Um sistema catalítico composto por Pd(OAc)2 e P(o-tol)3 foi aplicado na reação de Heck entre brometos de arila e diariletenos. Utilizando-se K2CO3 como base e DMF como solvente, olefinas triarilsubstituídas foram obtidas com rendimentos de bons a excelentes. Brometos de arila com substituintes eletr [...] oretiradores foram menos ativos para a reação de acoplamento Heck e levaram à formação de produto de homoacoplamento em quantidades substanciais, indicando que a adição oxidativa não deve ser a etapa lenta da reação. A presença de substituintes no diarileteno afetou drasticamente a seletividade da reação. Realizou-se também a dupla arilação do estireno, levando diretamente à olefina triarilsubstituída, com rendimento de 73%. Abstract in english A catalytic system composed of Pd(OAc)2 and P(o-tol)3 was found to be effective for the Heck reaction of aryl bromides with diarylethylenes. Using K2CO3 as a base and DMF as a solvent, trisubstituted olefins were obtained in good to excellent yields. Aryl bromides containing an electron-withdrawing [...] group in para position were less reactive for the Heck coupling reaction and gave substantial amount of homocoupling by-product suggesting that oxidative addition is not the rate-determining step. Electron withdrawing group substituent in the para position of stilbene affects the regioselectivity of the reaction. In this case, the phenyl group from the Ph-Pd complex migrates preferentially to the same carbon of the double bond to which the phenyl is bonded. Finally, a one pot sequential double Heck arylation of styrene was performed, giving trisubstituted olefin with an overall yield of 73%.