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Sample records for n-substituted aryl compounds

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

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

    2014-01-01

    The palladium(0)-catalyzed three-component coupling reaction of aryl bromides, carbon monoxide, and N-alkyl cyan­amides has been developed employing a two-chamber system with ex situ generation of carbon monoxide from a silacarboxylic acid. The reactions proceeded well and were complete with a...

  2. 40 CFR 721.9597 - Salt of a substituted sulfonated aryl azo compound (generic).

    2010-07-01

    ... azo compound (generic). 721.9597 Section 721.9597 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.9597 Salt of a substituted sulfonated aryl azo... substance identified generically as salt of a substituted sulfonated aryl azo compound (PMN P-00-0094)...

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

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

    2012-12-01

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

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

    Burkhard Koenig

    2011-01-01

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

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

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

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

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

    1988-09-27

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

  7. Aqueous high-temperature chemistry of carbo- and heterocycles. 29. Reactions of aryl hydrocarbons, aryl N-oxides and aryl carbonyl compounds in supercritical water at 460{degree}C

    Katritzky, A.R.; Ignatchenko, E.S.; Allin, S.M.; Barcock, R.A.; Siskin, M.; Hudson, C.W. [University of Florida, Gainesville, FL (United States). Center for Heterocyclic Compounds, Dept. of Chemistry

    1997-01-01

    A series of aryl hydrocarbons, aryl N-oxides, and aryl carbonyl compounds were subjected to thermolysis at 460{degree}C in water alone, in 15% aqueous formic acid, in 15% aqueous sodium formate, and, for comparison of purely thermal reactions, in cyclohexane. The runs were carried out initially for 7 min and, in most cases, also for 1 h. The aryl carbonyl substrates underwent mainly carbonyl reduction mainly under reduction conditions, with ring opening only observed in significant amounts for 1,4-naphthoquinone and 3,4-benzocoumarin. The arenes produced mainly reduction products with only low yields of ring-opened products observed. Aryl oximes underwent significant denitrogenation and subsequent reduction with only very little cleavage to simpler aromatic systems. The N-oxides underwent deoxygenation, and in the case of isoquinoline, ring opening of the heterocyclce was prevalent. 2-Aminobiphenyl was denitrogenated and cleaved to simpler systems in cyclohexane, but in the aqueous systems it underwent mainly cyclization to yield carbazole with only low yields of denitrogenated products. 2-Phenylphenol was unreactive under aqueous conditions with only low yields of deoxygenated products observed. 11 refs., 15 figs., 1 tab.

  8. Synthesis of O-glycosyl α-aryl nitrones

    Ying Fu; Huai Yuan Zhang; Yan Hua Liu; Xue Feng Li; Dan Feng Huang; Yu Lai Hu

    2010-01-01

    α-Aryl nitrone are one of the most useful kinds of nitrones and have been extensively explored in recent years.However,the sugar moieties have not been introduced into these molecules before.We presented here an efficient synthesis of α-aryl nitrone O-glycosides via condensation of N-substituted hydroxylamine and aryl aldehydes glycosides in benzene.

  9. Photophysical investigations on some synthesized electron donor aryl-bridged compounds

    Misra, T.; Maiti, M.; Saini, R.D.; Panda, S.K.; Ganguly, T

    2003-01-15

    The measurements of electronic absorption, steady-state fluorescence emission and time resolved transient spectra are made for two novel synthesized aryl-bridged compounds: 2,6-bis(4,5-dihydro-7,8-dimethoxy)-isoquinolino benzene(DIB) and 2,6-bis(4,5-dihydro-7,8-dimethoxy)-isoquinolino pyridine(DIP) at the ambient temperature in presence of the well-known electron acceptor 9-fluorenone (9FL). The energy positions of the absorption bands of both DIB and DIP are found to be similar to those of the corresponding bands of naphthalene and isoquinoline. Solvent effect shows that the two closely lying bands (260 and around 310 nm) of both DIB and DIP are of {pi}{pi}* type. Steady-state polarization experiments demonstrate that these two close-lying bands are responsible for two different type of transitions, 260 nm is responsible for {sup 1}L{sub a}<-{sup 1}A and 310 nm is due to {sup 1}L{sub b}<-{sup 1}A. This polarization study also shows that {sup 1}L{sub a} and {sup 1}L{sub b} bands are largely overlapping. Large bimolecular fluorescence quenching rates (k{sub q}{approx}10{sup 11} M{sup -1} s{sup -1}) observed from both intensity reduction and fluorescence lifetime quenching of the acceptor 9-fluorenone(9FL) in presence of the aryl-bridged donors indicate that the electron transfer (ET) radius is slightly greater than the hydrodynamic radius. The possibility of occurrence of some other fast non-radiative process along with photoinduced electron transfer whose possibility was tested by cyclic voltammetry measurements and presence was confirmed by laser flash photolysis study has been discussed. Transient absorption spectral measurements reveal that in the excited singlet (S{sub 1}) of 9FL photoinduced ET reaction is present but in its triplet (T{sub 1}) only energy transfer process is operative. Laser flash photolysis experiments provide the direct evidence for ion recombination mechanisms for production of monomeric triplets of both 9FL and the donors DIB and DIP.

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

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

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

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

    2015-01-01

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

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

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

    2015-01-01

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

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

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

    2015-06-15

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

  14. Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N-Substituted 2-Oxazolones.

    He, Yun; Agarwal, Piyush K; Kiran, I N Chaithanya; Yu, Ruocheng; Cao, Bei; Zou, Cheng; Zhou, Xinghua; Xu, Huacheng; Xu, Biao; Zhu, Lei; Lan, Yu; Nicolaou, K C

    2016-06-01

    A mild and practical method for the construction of heterocycles from N-substituted 2-oxazolones through cascade, BF3 ⋅Et2 O/H2 O-catalyzed reactions involving iminium ion generation and trapping by external or internal olefinic and aryl moieties is described. Mechanistic and computational studies revealed the strong protic acid HBF4 as the initiating catalyst for these cascade reactions. Providing access to novel molecular diversity, these processes may facilitate chemical biology studies, drug discovery efforts and natural products synthesis. PMID:27113382

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

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

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

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

    2015-01-15

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

  17. Biotransformation and Biodegradation of N-Substituted Aromatics in Methanogenic Granular Sludge.

    Razo Flores, E.

    1997-01-01

    N-substituted aromatic compounds are environmental contaminants associated with the production and use of dyes, explosives, pesticides and pharmaceuticals among others. Nitro- and azo-substituted aromatic compounds with strong electron withdrawing groups are poorly biodegradable in aerobic treatment systems. Therefore anaerobic treatment technologies were considered in this research. The toxicity of these compounds to methanogenic bacteria was studied. Batch toxicity assays indicated that nit...

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

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

  19. Synthesis, characterization and antiamoebic activity of chalcones bearing N-substituted ethanamine tail.

    Leeza Zaidi, Saadia; Mittal, Sonam; Rajala, Maitreyi S; Avecilla, Fernando; Husain, Mohammad; Azam, Amir

    2015-06-15

    A series of chalcones (4-21) possessing N-substituted ethanamine were synthesized by the aldol condensation reaction of 1-(4-(2-substituted ethoxy)phenyl)ethanones with different aldehydes preceded by the reaction of 2-chloro N-substituted ethanamine hydrochloride and 4-hydroxy acetophenone. The structure of all the synthesized compounds was elucidated by various spectral and X-ray diffraction studies. The compounds were screened against HM1: IMSS strain of Entamoeba histolytica and cytotoxicity was performed on A549 (non-small cell lung cancer cell line) cells by MTT assay. Out of eighteen compounds twelve showed better activity then the standard drug metronidazole. The compound 9, 14 and 19 showed good cell viability, hence were least toxic. PMID:26021707

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

    S.A.Katke

    2011-07-01

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

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

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

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

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

    1983-01-01

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

  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

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

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

    2013-01-01

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

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

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

    2013-05-01

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

  6. Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents

    Zhao, Xiao-Bo; Goto, Masuo; Song, Zi-Long; Morris-Natschke, Susan L.; Zhao, Yu; Wu, Dan; Yang, Liu; Li, Shu-Gang; Liu, Ying-Qian; Zhu, Gao-Xiang; Wu, Xiao-Bing; Lee, Kuo-Hsiung

    2014-01-01

    A series of novel 7-(N-substituted-methyl)-camptothecin derivatives was designed, synthesized, and evaluated for in vitro cytotoxicity against four human tumor cell lines, A-549, MDA-MB-231, KB, and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, with IC50 values ranging from 0.0023 to 1.11 μM, and were as or more potent than topotecan. Compounds 9d, 9e, and 9r exhibited the highest antiproliferative activity among all prepared d...

  7. Amino acid sequence of the ligand-binding domain of the aryl hydrocarbon receptor 1 predicts sensitivity of wild birds to effects of dioxin-like compounds.

    Farmahin, Reza; Manning, Gillian E; Crump, Doug; Wu, Dongmei; Mundy, Lukas J; Jones, Stephanie P; Hahn, Mark E; Karchner, Sibel I; Giesy, John P; Bursian, Steven J; Zwiernik, Matthew J; Fredricks, Timothy B; Kennedy, Sean W

    2013-01-01

    The sensitivity of avian species to the toxic effects of dioxin-like compounds (DLCs) varies up to 1000-fold among species, and this variability has been associated with interspecies differences in aryl hydrocarbon receptor 1 ligand-binding domain (AHR1 LBD) sequence. We previously showed that LD(50) values, based on in ovo exposures to DLCs, were significantly correlated with in vitro EC(50) values obtained with a luciferase reporter gene (LRG) assay that measures AHR1-mediated induction of cytochrome P4501A in COS-7 cells transfected with avian AHR1 constructs. Those findings suggest that the AHR1 LBD sequence and the LRG assay can be used to predict avian species sensitivity to DLCs. In the present study, the AHR1 LBD sequences of 86 avian species were studied, and differences at amino acid sites 256, 257, 297, 324, 337, and 380 were identified. Site-directed mutagenesis, the LRG assay, and homology modeling highlighted the importance of each amino acid site in AHR1 sensitivity to 2,3,7,8-tetrachlorodibenzo-p-dioxin and other DLCs. The results of the study revealed that (1) only amino acids at sites 324 and 380 affect the sensitivity of AHR1 expression constructs of the 86 avian species to DLCs and (2) in vitro luciferase activity of AHR1 constructs containing only the LBD of the species of interest is significantly correlated (r (2) = 0.93, p toxicity data for those species. These results indicate promise for the use of AHR1 LBD amino acid sequences independently, or combined with the LRG assay, to predict avian species sensitivity to DLCs. PMID:22923492

  8. Toxicity and biodegradability of selected N-substituted phenols under anaerobic conditions

    Donlon, B.; Razo-Flores, E.; Hwu, C.S.; Field, J.; Lettinga, G. [Wageningen Agricultural Univ. (Netherlands)

    1995-12-31

    The anaerobic toxicity and biodegradability of N-substituted aromatics were evaluated in order to obtain information on their ultimate biotreatment. The toxicity of selected N-substituted aromatic compounds toward acetoclastic methanogens in granular sludge was measured in batch assays. This toxicity was highly correlated with compound hydrophobicity, indicating that partitioning into the bacterial membranes was an important factor in the toxicity. However, other factors, such as chemical interactions with key cell components, were suggested to be playing an important role. Nitroaromatic compounds were, on the average, over 300-fold more toxic than their amino-substituted counterparts. This finding suggests that the facile reduction of nitro-groups known to occur in anaerobic environments would result in a high level of detoxification. To test this hypothesis, continuous lab-scale upward-flow anaerobic sludge bed reactors treating 2-nitrophenol and 4-nitrophenol were established. The 4-nitrophenol was readily converted to the corresponding 4-aminophenol, whereas complete mineralization of 2-nitrophenol via intermediate formation of 2-aminophenol was obtained. These conversions led to a dramatic detoxification of the nitrophenols, because it was feasible to treat the highly toxic nitrophenolics at high organic loading rates.

  9. Modern Arylation Methods

    Ackermann, Lutz

    2009-01-01

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

  10. Transition Metal Catalyzed Synthesis of Aryl Sulfides

    Chad C. Eichman

    2011-01-01

    Full Text Available The presence of aryl sulfides in biologically active compounds has resulted in the development of new methods to form carbon-sulfur bonds. The synthesis of aryl sulfides via metal catalysis has significantly increased in recent years. Historically, thiolates and sulfides have been thought to plague catalyst activity in the presence of transition metals. Indeed, strong coordination of thiolates and thioethers to transition metals can often hinder catalytic activity; however, various catalysts are able to withstand catalyst deactivation and form aryl carbon-sulfur bonds in high-yielding transformations. This review discusses the metal-catalyzed arylation of thiols and the use of disulfides as metal-thiolate precursors for the formation of C-S bonds.

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

    Patil S

    2013-05-01

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

  12. Design,Synthesis and Biological Activity of Ethyl 2-(N-Substituted-arylsulfonamido)-2-oxoacetate

    WANG Bao-lei; WU Jing; HE Feng-qi; LI Yon-ghong; LI Zheng-ming

    2008-01-01

    Thirteen new ethyl 2-(N-substituted-arylsulfonamido)-2-oxoacetates(3a-3m),based on the structure of Ketol-acid reductoisomerase(KARI) inhibitor IpOHA,were designed and synthesized,Their structures were established on the basis of 1H NMR,IR,MS,and elemental analyses,The bioassay result reveals that the structural changes from hydroxyl group on the N atom of IpOHA to arylsulfonyl groups does not enhance the inhibitory activity of the compounds to KARI in vitro,Compounds 3c,3h,3k,and 3m are more effective than IpOHA against the monocotyledonous barnygrass at 100 μg/mL in herbicidal tests.

  13. Evidence of N substitution by Mn in GaN

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

    2012-01-01

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

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

    Saman Damavandi; Reza Sandaroos

    2013-01-01

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

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

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

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

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

    2016-04-01

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

  17. A Simple and Facile Approach to Aliphatic N-Substituted Functional Eight-Membered Cyclic Carbonates and Their Organocatalytic Polymerization.

    Venkataraman, Shrinivas; Ng, Victor W L; Coady, Daniel J; Horn, Hans W; Jones, Gavin O; Fung, Tak Shun; Sardon, Haritz; Waymouth, Robert M; Hedrick, James L; Yang, Yi Yan

    2015-11-01

    Aliphatic N-substituted functional eight-membered cyclic carbonates were synthesized from N-substituted diethanolamines by intramolecular cyclization. On the basis of the N-substituent, three major subclasses of carbonate monomers were synthesized (N-aryl, N-alkyl and N-carbamate). Organocatalytic ring opening polymerization (ROP) of eight-membered cyclic carbonates was explored as a route to access narrowly dispersed polymers of predictable molecular weights. Polymerization kinetics was highly dependent on the substituent on the nitrogen atom and the catalyst used for the reaction. The use of triazabicyclodecene (TBD), instead of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), as the catalyst for the N-alkyl substituted monomers significantly enhanced the rate of polymerizations. Computational studies were performed to rationalize the observed trends for TBD catalyzed polymerizations. With the optimal organocatalyst all monomers could be polymerized generating well-defined polymers within a timespan of ≤2 h with relatively high monomer conversion (≥80%) and low molar-mass dispersity (Đ(M) ≤ 1.3). Both the glass transition temperatures (T(g)) and onset of degradation temperatures (T(onset)) of these polymers were found to be N-substituent dependent and were in the range of about -45 to 35 °C and 230 to 333 °C, respectively. The copolymerization of the eight membered monomers with 6-membered cyclic comonomers including commercially available l-lactide and trimethylene carbonate produced novel copolymers. The combination of inexpensive starting materials, ease of ring-closure and subsequent polymerization makes this an attractive route to functional polycarbontes. PMID:26456146

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

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

    2004-09-01

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

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

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

    1988-03-01

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

  20. Playing with isomerism and N substitution in pentalenedione derivatives for organic electrode batteries: how high are the stakes?

    Tomerini, Daniele; Gatti, Carlo; Frayret, Christine

    2016-01-28

    New concepts to design innovating and top-performing redox-active organic molecules based electrodes should push forward and promote an eco-friendly alternative to classical Li-ion batteries. In this promising research area, density functional theory calculations lend support to experiments through the prediction of redox voltage and give promise to rationalize the trends, thus providing a general approach for engineering advanced materials. In this study in which we analysed spin density/net atomic charges distribution along with global energy decomposition thanks to Bader's partitioning of the molecular space, a vision for designing pentalenedione derivatives by fine tuning of the redox potential properties is presented. The concept relies on combined effects of isomerism and N single/double substitution for CH on the parent backbone. Such dual nature modification is able to provide a series of compounds within the range of 2.2-3.6 V vs. Li(+)/Li (against a more restricted range of 2.2-2.8 V vs. Li(+)/Li for the sole effect of isomerism on the unsubstituted parent compounds). The incidence of double N substitution alone generally follows an almost additive rule based on the combined actions of the composing single N substitutions. Few exceptions to the rule were, however, also observed and rationalized. Beyond learning gained for this peculiar family, these results may have exciting implications for future design strategies. PMID:26701642

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

    Al-Balas QA

    2014-01-01

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

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

    Liu, Yi; He, Lin [Guandong Pharmaceutical Univ., Zhongshan (China); Yin, Guoqiang; Wu, Guojie; Cui, Yingde [Zhongkai Univ. of Agriculture and Engineering, Guangzhou (China)

    2013-08-15

    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.

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

    Ling Yang

    2011-12-01

    Full Text Available The nociceptin/orphanin FQ (NOP receptor is involved in a wide range of biological functions, including pain, anxiety, depression and drug abuse. Especially, its agonists have great potential to be developed into anxiolytics. In this work, both the ligand- and receptor-based three-dimensional quantitative 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.

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

    Fetsch, Corinna

    2011-09-13

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

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

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

  6. Palladium-Catalyzed α-Arylation of Aryl Acetic Acid Derivatives via Dienolate Intermediates with Aryl Chlorides and Bromides

    Sha, Sheng-Chun; Zhang, Jiadi; Walsh, Patrick J.

    2015-01-01

    To date, examples of α-arylation of carboxylic acids remain scarce. Using a deprotonative cross-coupling process (DCCP), a method for palladium-catalyzed γ-arylation of aryl acetic acids with aryl halides has been developed. This protocol is applicable to a wide range of aryl bromides and chlorides. A procedure for the palladium-catalyzed α-arylation of styryl acetic acids is also described.

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

    Mazaahir Kidwai; Saurav Bhardwaj; Roona Poddar

    2010-01-01

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

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

    Mazaahir Kidwai

    2010-04-01

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

  9. N-Substituted Derivatives of the Azadithiolate Cofactor from the [FeFe] Hydrogenases: Stability and Complexation.

    Angamuthu, Raja; Chen, Chi-Shian; Cochrane, Tyler R; Gray, Danielle L; Schilter, David; Ulloa, Olbelina A; Rauchfuss, Thomas B

    2015-06-15

    Experiments are described that probe the stability of N-substituted derivatives of the azadithiolate cofactor recently confirmed in the [FeFe] hydrogenases (Berggren, G., et al. Nature 2013, 499, 66). Acid-catalyzed hydrolysis of bis(thioester) BnN(CH2SAc)2 gives [BnNCH2SCH2]2 rather than azadithiol BnN(CH2SH)2. Treatment of BnN(CH2SAc)2 with NaO(t)Bu generates BnN(CH2SNa)2, which was trapped with NiCl2(diphos) (diphos = 1,2-C2H4(PR2)2; R = Ph (dppe) and Cy (dcpe)) to give fully characterized complexes Ni[(SCH2)2NBn](diphos). The related N-aryl derivative Ni[(SCH2)2NC6H4Cl](diphos) was prepared analogously from 4-ClC6H4N(CH2SAc)2, NaO(t)Bu, and NiCl2(dppe). Crystallographic analysis confirmed that these rare nonbridging [adt(R)](2-) complexes feature distorted square planar Ni centers. The analogue Pd[(SCH2)2NBn](dppe) was also prepared. (31)P NMR analysis indicates that Ni[(SCH2)2NBn](dppe) has basicity comparable to typical amines. As shown by cyclic voltammetry, the couple [M[(SCH2)2NBn](dppe)](+/0) is reversible near -2.0 V versus Fc(+/0). The wave shifts to -1.78 V upon N-protonation. In the presence of CF3CO2H, Ni[(SCH2)2NBn](dppe) catalyzes hydrogen evolution at rate of 22 s(-1) in the acid-independent regime, at room temperature in CH2Cl2 solution. In contrast to the instability of RN(CH2SH)2 (R = alkyl, aryl), the dithiol of tosylamide TsN(CH2SH)2 proved sufficiently stable to allow full characterization. This dithiol reacts with Fe3(CO)12 and, in the presence of base, NiCl2(dppe) to give Fe2[(SCH2)2NTs](CO)6 and Ni[(SCH2)2NTs](dppe), respectively. PMID:26000618

  10. Alkylation and 1,3-Dipolar Cycloaddition of 6-Styryl-4,5-dihydro-2H-pyridazin-3-one: Synthesis of Novel N-Substituted Pyridazinones and Triazolo[4,3-b]pyridazinones

    José A. S. Cavaleiro; Maria A.F. Faustino; Neves, Maria G. P. M. S.; El Mostapha Rakib; Hanan Sekkak; Souad Mojahidi; Hafid Zouihri

    2013-01-01

    Some new N-substituted pyridazinones and triazolo[4,3-b]pyridazinones were synthesized, respectively, by simple alkylation and 1,3-dipolar cycloaddition of pyridazin-3-one with nitrile imines. The regioselectivity of the reactions was ascertained by 1H, 13C NMR spectroscopy and X-ray diffraction of the synthesized compounds.

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

    Jensen, Thomas; Pedersen, Henrik; Bang-Andersen, B.;

    2008-01-01

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

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

    Aziz-ur-Rehman

    2014-03-01

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

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

    *Aziz-ur-Rehman

    2013-03-01

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

  14. Direct N9-arylation of purines with aryl halides

    Larsen, Anders Foller; Ulven, Trond

    2014-01-01

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

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

    Agrawal, Toolika; Cook, Silas P

    2014-10-01

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

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

    Wu, Linglin

    2012-02-06

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

  17. Iron-Mediated Direct Arylation of Unactivated Arenes in Air

    Huang, Yuxing; Moret, Marc-Etienne; Klein Gebbink, Bert

    2014-01-01

    Biaryls are a common motif in both natural and synthetic chemicals. Several methods have recently been reported for the preparation of these compounds using direct arylation catalyzed by iron, other base metals, or transition-metal-free systems. To date, these methods have all required inert and/or

  18. Aryl diazonium salts new coupling agents and surface science

    Chehimi, Mohamed Mehdi

    2012-01-01

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

  19. Inhibition of Bfl-1 with N-Aryl Maleimides

    Cashman, John R.; MacDonald, Mary; Ghirmai, Senait; Okolotowicz, Karl J.; Sergienko, Eduard; Brown, Brock; Garcia, Xochella; Zhai, Dayong; John C Reed

    2010-01-01

    High throughput screening of 66,000 compounds using competitive binding of peptides comprising the BH3 domain to anti-apoptotic Bfl-1 led to the identification of fourteen validated “hits” as inhibitors of Bfl-1. N-Aryl maleimide 1 was among the validated “hits”. A chemical library encompassing over 280 analogs of 1 was prepared following a two-step synthesis. Structure-activity studies for inhibition of Bfl-1 by analogs of N-aryl maleimide 1 revealed a preference for electron-withdrawing sub...

  20. Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents: synthesis and bioactivity

    Wen-yuan YU; Li-xia YANG; Jian-shu XIE; Ling ZHOU; Xue-yuan JIANG; De-xu ZHU; Mutsumi MURAMATSU; Ming-wei WANG

    2008-01-01

    Aim: The aim of the present study was to design, synthesize, and evaluate novel antibacterial agents, derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide. Methods: A total of 44 derivatives of aryl-4-guanidin-omethylbenzoate (series A) and N-aryl-4-guanidinomethylbenzamide (series B) were synthesized and their antibacterial activities were assessed in vitro against a variety of Gram-positive and Gram-negative bacteria by an agar dilution method. Results: Twelve compounds showed potent bactericidal effects against a panel of Gram-positive germs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), vancomycin-intermediate Sta-phylococcus aureus (VISA), and methicillin-resistant coagulase-negative staphy-lococci (MRCNS), with minimum inhibitory concentrations (MIC) ranging be-tween 0.5 and 8 μg/mL, which were comparable to the MIC values of several marketed antibiotics. They exhibited weak or no activity on the Gram-negative bacteria tested. In addition, these compounds displayed high inhibitory activities towards oligopeptidase B of bacterial origin. Conclusion: In comparison with the previ-ously reported MIC values of several known antibiotics, the derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide showed com-parable in vitro bactericidal activities against VRE and VISA as linezolid. Their growth inhibitory effects on MRSA were similar to vancomycin, but were less potent than linezolid and vancomycin against MRCNS. This class of compounds may have the potential to be developed into narrow spectrum antibacterial agents against certain drug-resistant strains of bacteria.

  1. Gold-Catalyzed Direct Arylation

    Ball, L. T.; Lloyd-jones, G. C.; Russell, C. A.

    2012-01-01

    Biaryls (two directly connected aromatic rings, Ar1-Ar2) are common motifs in pharmaceuticals, agrochemicals, and organic materials. Current methods for establishing the Ar1-Ar2 bond are dominated by the cross-coupling of aryl halides (Ar1-X) with aryl metallics (Ar2-M). We report that, in the presence of 1 to 2 mole percent of a gold catalyst and a mild oxidant, a wide range of arenes (Ar1-H) undergo site-selective arylation by arylsilanes (Ar2-SiMe3) to generate biaryls (Ar1-Ar2), with litt...

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

    Antonio Monge

    2009-10-01

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

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

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

  4. Synthesis of Some N-Substituted Sulfonamides Derived from Moringine as Lipoxygenase Inhibitors

    *M. A. Abbasi

    2014-12-01

    Full Text Available Sulfonamides belong to an emerging class having good inhibitory effects. In the present work, a series of N-substituted derivatives of N-benzyl-4-chlorobenzenesulfonamide have been synthesized. The reaction of moringine (benzylamine; 1 with 4-chlorobenzenesulfonyl chloride (2 in aqueous medium yielded the parent molecule, N-benzyl-4-chlorobenzenesulfonamide (3. Alkyl/aralkyl halides, 4a-m, were reacted with 3 in polar aprotic medium to produce N-substituted derivatives, 5a-m. These synthesized products were characterized by 1H-NMR, IR and EI-MS spectra and screened against lipoxygenase (LOX enzyme. These were found to be moderate inhibitors of this enzyme and could find their use as therapeutic agent for various inflammatory ailments.

  5. Synthesis, Spectral Characterization and biological activity of N-Substituted Derivatives of Tetrahydrofuran-2-ylmethylamine

    Aziz-ur-Rehman; Rasool, S; Abbasi, M. A.; Khan, K. M.; Ahmad, I.; 2S. Afzal

    2014-01-01

    Tetrahydrofuran-2-ylmethylamine (1) was subjected to condensation reaction with 4-chlorobenzenesulfonyl chloride (2) in a mild basic medium to synthesize N-(tetrahydrofuran-2-ylmethyl)-4-chlorobenzenesulfonamide (3). A series of N-substituted derivatives, 5a-f, were synthesized by condensing alkyl/aralkyl halides, 4a-f, with 3 under polar aprotic conditions using sodium hydride activator. The spectral characterization of all the molecules included IR, 1H-NMR and EI-MS data. The biological act...

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

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

    2015-01-01

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

  7. An Improved Protocol for the Pd-catalyzed α-Arylation of Aldehydes with Aryl Halides

    Martín, Rubén; Buchwald, Stephen L.

    2008-01-01

    An improved protocol for the Pd-catalyzed α-arylation of aldehydes with aryl halides has been developed. The new catalytic system allows for the coupling of an array of substrates including challenging electron-rich aryl bromides and less reactive aryl chlorides. The utility of this method has been demonstrated in a new total synthesis of (±)-sporochnol.

  8. Systematic Synthesis and Characterization of a Series of Tetra(5-aryl-2-thienyl)thiophenes

    Muraoka, Hiroki; Tanifuji, Takanori; Ogawa, Satoshi

    2011-01-01

    We have succeeded in the synthesis of a series of tetra(5-aryl-2-thienyl)thiophenes as aryl-functionalized tetrathienylthiophenes. Characterization of these chemicals was performed by physical and spectroscopic means. The electrochemical properties were examined by cyclic voltammetry. The CV of all compounds showed that the redox behavior and potentials were controlled by the electronic effect of the p-substituted phenyl groups introduced at the outer α-positions on the four thiophene units l...

  9. 2-Alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT2A antagonists.

    Shireman, Brock T; Dvorak, Curt A; Rudolph, Dale A; Bonaventure, Pascal; Nepomuceno, Diane; Dvorak, Lisa; Miller, Kirsten L; Lovenberg, Timothy W; Carruthers, Nicholas I

    2008-03-15

    The synthesis and SAR for a novel series of 2-alkyl-4-aryl-tetrahydro-pyrido-pyrimidines and 2-alkyl-4-aryl-tetrahydro-pyrimido-azepines is described. Representative compounds were shown to be subtype selective 5-HT(2A) antagonists. Optimal placement of a basic nitrogen relative to the pyrimidine and the presence of a 4-fluorophenyl group in the pyrimidine 4-position was found to have a profound effect on affinity and selectivity. PMID:18282705

  10. Synthesis, Spectral Characterization and biological activity of N-Substituted Derivatives of Tetrahydrofuran-2-ylmethylamine

    Aziz-ur-Rehman

    2014-06-01

    Full Text Available Tetrahydrofuran-2-ylmethylamine (1 was subjected to condensation reaction with 4-chlorobenzenesulfonyl chloride (2 in a mild basic medium to synthesize N-(tetrahydrofuran-2-ylmethyl-4-chlorobenzenesulfonamide (3. A series of N-substituted derivatives, 5a-f, were synthesized by condensing alkyl/aralkyl halides, 4a-f, with 3 under polar aprotic conditions using sodium hydride activator. The spectral characterization of all the molecules included IR, 1H-NMR and EI-MS data. The biological activity evaluation rendered 5c as moderate inhibitor of all the bacterial strains.

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

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

    2014-12-19

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

  12. A combined experimental and theoretical study of the thermal cycloaddition of aryl azides with activated alkenes.

    Zeghada, Sarah; Bentabed-Ababsa, Ghenia; Derdour, Aïcha; Abdelmounim, Safer; Domingo, Luis R; Sáez, José A; Roisnel, Thierry; Nassar, Ekhlass; Mongin, Florence

    2011-06-01

    Reactions were performed from aryl azides on the one hand, and activated alkenes coming from β-dicarbonyl compounds or malonodinitrile on the other hand, either with recourse to conventional heating or to microwave activation, to afford 1-aryl-1H-1,2,3-triazoles. The mechanism and the regioselectivity of the reactions involving β-dicarbonyl compounds have been theoretically studied using DFT methods at the B3LYP/6-31G* level: they are domino processes comprising a tautomeric equilibrium of the β-dicarbonyl compounds with their enol forms, a 1,3-dipolar cycloaddition of the enol forms with the aryl azides (high activation energy), and a dehydration process (lower activation energy). The effect of non-conventional activation methods on the degradation of 1,2,3-triazolines was next studied experimentally. Finally, some of the 1,2,3-triazoles such synthesized were evaluated for their bactericidal and cytotoxic activities. PMID:21494704

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

    2007-11-01

    Full Text Available Quaternary ammonium ionomers of Methacrylamidopropyltrimethyl ammonium chloride with N-substituted acrylamides were prepared at 55±1°C using azobiscyanovaleric acid (ACVA initiator. The monomers and ionomers were characterized by 1H- and 13C-NMR spectroscopy and the copolymer composition was calculated from elemental analysis data. The reduced viscosity of ionomers in methanol behaves as non-polyelectrolytes at lower mole percentage and as polyelectrolyte at higher mole percentage. The molecular weights of ionomers were found to be high and the polydispersity index values indicate termination mainly by disproportionation. The glass transition temperature (Tg of ionomers were greater than those of the corresponding homopolymers, attributed to a reduction in segmental mobility. The initial decomposition temperature (IDT showed that the stability of ionomers increases with increasing mole percentage of ionic content.

  14. N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase.

    Maccallini, Cristina; Patruno, Antonia; Lannutti, Fabio; Ammazzalorso, Alessandra; De Filippis, Barbara; Fantacuzzi, Marialuigia; Franceschelli, Sara; Giampietro, Letizia; Masella, Simona; Felaco, Mario; Re, Nazzareno; Amoroso, Rosa

    2010-11-15

    A series of N-substituted acetamidines and 2-methylimidazole derivatives structurally related to W1400 were synthesized and evaluated as Nitric Oxide Synthase (NOS) inhibitors. Analogs with sterically hindering isopropyl and phenyl substituents on the benzylic carbon connecting the aromatic core of W1400 to the acetamidine nitrogen, showed good inhibitory potency for nNOS (IC(50)=0.2 and 0.3 μM) and selectivity over eNOS (500 and 1166) and to a lesser extent over iNOS (50 and 100). A molecular modeling study allowed to shed light on the effects of the structural modifications on the selectivity of the designed inhibitors toward the different NOS isoforms. PMID:20933416

  15. A combined experimental and theoretical study of the thermal cycloaddition of aryl azides with activated alkenes.

    Zeghada, Sarah; Bentabed-Ababsa, Ghenia; Derdour, Aïcha; Abdelmounim, Safer; Domingo, Luis .R.; Sáez, José A.; Roisnel, Thierry; Nassar, Ekhlass; Mongin, Florence

    2011-01-01

    Reactions were performed from aryl azides on the one hand, and activated alkenes coming from β-dicarbonyl compounds or malonodinitrile on the other hand, either with recourse to conventional heating or to microwave activation, to afford 1-aryl-1H-1,2,3-triazoles. The mechanism and the regioselectivity of the reactions involving β-dicarbonyl compounds have been theoretically studied using DFT methods at the B3LYP/6-31G* level: they are domino processes comprising a tautomeric equilibrium of th...

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

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

    2013-06-15

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

  17. A New Biocatalyst for Production of Optically Pure Aryl Epoxides by Styrene Monooxygenase from Pseudomonas fluorescens ST

    Di Gennaro, Patrizia; Colmegna, Andrea; Galli, Enrica; Sello, Guido; Pelizzoni, Francesca; Bestetti, Giuseppina

    1999-01-01

    We developed a biocatalyst by cloning the styrene monooxygenase genes (styA and styB) from Pseudomonas fluorescens ST responsible for the oxidation of styrene to its corresponding epoxide. Recombinant Escherichia coli was able to oxidize different aryl vinyl and aryl ethenyl compounds to their corresponding optically pure epoxides. The results of bioconversions indicate the broad substrate preference of styrene monooxygenase and its potential for the production of several fine chemicals. PMID:10347083

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

    Boopathy Rathanam

    2000-12-01

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

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

    1S. Nadeem

    2014-09-01

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

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

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

    2016-06-01

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

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

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

    2012-05-01

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

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

    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.

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

    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

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

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

    2013-12-01

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

  5. Synthesis and Pregnancy Terminating Activity of 2-Aryl imidazo [2,1-a] isoquinolines

    2001-01-01

    Two 2-aryl imidazo [2,1-a] isoquinolines were synthesized and tested for pregnancy terminating activities. Both of them are new compounds and their structures were confirmed by IR, 1HNMR, MS and elemental analysis. They both showed high activities in NIH mice.

  6. Copper-Catalyzed 2,2,2-Trifluoroethylthiolation of Aryl Halides.

    Chen, Shouxiong; Zhang, Mengjia; Liao, Xuebin; Weng, Zhiqiang

    2016-09-01

    Herein, a copper-catalyzed 2,2,2-trifluoroethylthiolation reaction of aryl bromides and iodides with elemental sulfur, and 1,1,1-trifluoro-2-iodoethane is described. The reaction showed excellent functional group tolerance and allowed the synthesis of various substituted aryl 2,2,2-trifluoroethyl thioethers with good to excellent yields. This transformation constitutes a one-pot synthesis of 2,2,2-trifluoroethylthiolated compounds from inexpensive, readily available starting materials. Utility of the protocol was further demonstrated in the late-stage synthesis of the pirfenidone derivative. The copper thiolate species were prepared and proposed as key intermediates in the catalytic cycle. PMID:27477255

  7. Facile synthesis, characterization and antimicrobial activities of diphenylphosphoryl derivatives of substituted aryl and nitrogen heterocycles

    G. Subba Reddy

    2013-03-01

    Full Text Available Diphenylphosphoryl derivatives of substituted aryl and nitrogen heterocycles were prepared by a one-pot process involving sequential reaction of diphenylphosphine chloride with dry methyl alcohol/ethyl alcohol and then with different halides of substituted nitrogen heterocycles/aryl halides. The title compounds (5a-j structures were established by analytical, IR, NMR ( 1H, 13C and 31P and mass spectra, and they have been screened for their antimicrobial activity. They exhibited significant antibacterial and antifungal activity.

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

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

    1995-12-31

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

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

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

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

    Henok H. Kinfe

    2015-04-01

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

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

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

    2013-01-01

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

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

    Zhiling Cao

    2013-12-01

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

  13. Nickel-catalyzed reductive arylation of activated alkynes with aryl iodides

    Dorn, Stephanie C. M.; Olsen, Andrew K; Kelemen, Rachel E.; Shrestha, Ruja; Weix, Daniel J.

    2015-01-01

    The direct, regioselective, and stereoselective arylation of activated alkynes with aryl iodides using a nickel catalyst and manganese reductant is described. The reaction conditions are mild (40 °C in MeOH, no acid or base) and an intermediate organomanganese reagent is unlikely. Functional groups tolerated include halides and pseudohalides, free and protected anilines, and a benzyl alcohol. Other activated alkynes including an amide and a ketone also reacted to form arylated products in good yields. PMID:26028781

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

    Yan, Qi; Ding, Ning; Li, Yingxia

    2016-02-01

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

  15. Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

    Akahoshi Eiichi; Yoshimura Seiko; Uruno Saeko; Ishihara-Sugano Mitsuko

    2009-01-01

    Abstract Background Dioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (...

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

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

    2016-01-01

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

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

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

    2015-06-01

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

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

    Aurea Echevarria

    2012-11-01

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

  19. One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

    Joshua P. Barham

    2014-12-01

    Full Text Available Nucleophilic trapping of iminium salts generated via oxidative functionalisation of tertiary amines is well established with stabilised carbon nucleophiles. The few reports of organometallic additions have limited scope of substrate and organometallic nucleophile. We report a novel, one-pot methodology that functionalises N-substituted tetrahydroisoquinolines by visible light-assisted photooxidation, followed by trapping of the resultant iminium ions with organometallic nucleophiles. This affords 1,2-disubstituted tetrahydroisoquinolines in moderate to excellent yields.

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

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

    2013-11-01

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

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

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

  2. 9-Aryl Substituted Hydroxylated Xanthen-3-ones: Synthesis, Structure and Antioxidant Potency Evaluation

    Veljović, Elma; Špirtović-Halilović, Selma; Muratović, Samija; Valek Žulj, Lidija; Roca, Sunčica; Trifunović, Snežana; Osmanović, Amar; Završnik, Davorka

    2015-01-01

    Oxidative stress is directly related to several diseases and symptoms, where antioxidant compounds, such as xanthenes, may become important in prevention and/or treatmant. Ten biologically active 9-aryl substituted 2,6,7-trihydroxyxanthen-3-one derivatives were synthesized using reliable one-pot synthesis and their structures were confirmed by IR, 1H and 13C NMR spectroscopy and mass spectrometry. Some of the synthesized compounds were scanned for their antioxidant potency using electrochemic...

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

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

    2011-07-01

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

  4. Palladium-catalysed ortho arylation of acetanilides

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

    2010-03-01

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

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

    Anjan Chattopadhyay

    2012-09-01

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

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

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

    2007-01-01

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

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

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

    1986-07-01

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

  8. Proton And Carbon-13 Nuclear Magnetic Resonance Of Some 4-Amino-3-Alkyl (Aryl)-5-Thio-1,2,4-Triazolines And Their Derivatives

    El Toukhy, Ahmed [احمد الطوخي; Al-Kubaisi, Abdulla H.; Kenawy, Ibrahim

    1991-01-01

    The proton and carbon-13 NMR spectra of some 4-amino-3-alkyl(aryl)-5-thio-1,2,4-triazolines, some 3-alkyl-5-thio- 1,2,4-triazolines and some 4-amino-3-aryl-5-thio-l,2,4-triazoles were measured in DMSO-d6 as solvent. The chemical shift for each proton and carbon in these compounds were assigned. The 'H, chemical shift of N-H protons of the thioamide group and the "C chemical shift of C(3) in the triazolines were found to be sensitive to the substituent R (alkyi or aryl) at C(3), and correlated...

  9. Design,synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives

    Jian LI; Bing XIONG; Xi-shan XIONG; Hong LIU; Xiao-min LUO; Hua-liang JIANG; Jin-zhi TAN; Li-li CHEN; Jian ZHANG; Xu SHEN; Chang-lin MEI; Li-li FU; Li-ping LIN; Jian DING

    2006-01-01

    Aim: To design and synthesize a novel class of protein tyrosine kinase inhibitors, featuring the N-(2-oxo-1,2-dihydroquinolin-3-yl-methyl)-thiourea framework. Methods: First, compounds 1 and 2 were identified using the virtual screening approach in conjunction with binding assay based on surface plasmon resonance. Subsequently, 3 regions of compounds 1 and 2 were selected for chemical modification. All compounds were characterized potent inhibitory activities toward the human lung adenocarcinoma cell line SPAC1. Results: Forty new compounds (1-2, 3a-g, 4a-w, and 5a-l) were designed, synthesized and bioassayed. Six compounds (1, 3e, 41,4w, 5a, and 5b) were found to show promising inhibitory activity against the SPAC1 tumor cell line. The inhibitory activity of compound 5a increases approximately 10 times more than that of the original compound 1. Conclusion: This study provides a promising new template with potential antitumor activity.

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

    *Aziz-ur-Rehman

    2013-06-01

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

  11. The Remarkable Reactivity of Aryl Halides with Nucleophiles

    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)

  12. Decarboxylative and direct functionalisations of aromatic compounds

    Seo, Sangwon

    2014-01-01

    Aromatic rings are privileged structures found in a diverse range of natural and synthetic compounds, thus synthetic methods for their functionalisations are important in organic synthesis. Despite significant advancements made, especially in the field of transition metal catalysis, work still continues for the development of milder, more efficient, and more atom economical reactions. We describe here our efforts towards the development of decarboxylative/direct C(aryl)–N and C(aryl)–C bond f...

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

    Al-Abdullah ES

    2014-05-01

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

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

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

    2016-03-01

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

  15. Tuning of the charge in octahedral ferric complexes based on pyridoxal-N-substituted thiosemicarbazone ligands

    Tido, Eddy W. Yemeli; Faulmann, Christophe; Roswanda, Robby; Meetsma, Auke; van Koningsbruggen, Petra J.

    2010-01-01

    Four novel mononuclear coordination compounds namely: [Fe(Hthpy)(2)](SO(4))(1/2)center dot 3.5H(2)O 1, [Fe(Hthpy)(2)]NO(3)center dot 3H(2)O 2, [Fe(H(2)mthpy)(2)](CH(3)C(6)H(4)SO(3))(3)center dot CH(3)CH(2)OH 3 and [Fe(Hethpy)(ethpy)]center dot 8H(2)O 4, (H(2)thpy = pyridoxalthiosemicarbazone, H(2)mthpy = pyridoxal-4-methylthiosemicarbazone, H(2)ethpy = pyridoxal-4-ethylthiosemicarbazone), were synthesized in the absence or presence of organic base, Et(3)N and NH(3). Compounds 1 and 2 are mono...

  16. Electronic structure and tautomerism of aryl ketones

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

    2015-07-15

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

  17. Antibacterial, antifungal and cytotoxic properties of novel N-substituted sulfonamides from 4-hydroxycoumarin.

    Chohan, Zahid H; Shaikh, Ali U; Rauf, Abdul; Supuran, Claudiu T

    2006-12-01

    A new series of 4-({[2, 4-dioxo-2H-chromen-3 (4H)-ylidene] methyl} amino) sulfonamides have been obtained by the condensation reaction of 4-hydroxycoumarin with various sulfonamides (sulfanilamide, sulfaguanidine, p-aminomethyl-sufanilamide, p-aminoethylsufanilamide, sulfathiazole, sulfamethoxazole, sulfamethazine and 4-[(2-amino-4-pyrimidinyl) amino] benzenesulfonamide) in the presence of an excess of ethylorthoformate. These compounds were screened for their in-vitro antibacterial activity against four Gram-negative (E. coli, S. flexneri, P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) bacterial strains and for in-vitro antifungal activity against T. longifusus, C. albicans, A. flavus, M. canis, F. solani and C. glaberata. Results revealed that a significant antibacterial activity was observed by compounds (4) and (5), (6) and (8) against two Gram-negative, (P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) species, respectively. Of these (4) was found to be the most active. Similarly, for antifungal activity compounds (3) and (8) showed significant activity against M. canis and, (6) and (8) against F. solani. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and only two compounds, (4) and (8) possessing LD50 = 2.9072 x 10(-4) and 3.2844 x 10(-4) M, respectively, displayed potent cytotoxic activity against Artemia salina PMID:17252948

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

    Isaivani Dhinakaran; Vediappen Padmini; Nattamai Bhuvanesh

    2015-12-01

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

  19. The impact of cytochrome P4501-inhibitors on aryl hydrocarbon receptor signaling

    Bengtsson, Johanna

    2016-01-01

    The aryl hydrocarbon receptor (AHR) best known as a ligand-activated transcription factor that mediates toxic responses to xenobiotics such as dioxins, is also activated by certain endogenous compounds. Activation of the AHR up-regulates transcription of a large number of genes, including those encoding members of the cytochrome P450 1 family of enzymes (CYP1s). Although the AHR has been shown to be involved in several normal processes, its physiological role remains elusive. The endogenous l...

  20. Methanofullerene-Based Palladium Bis(amino)aryl Complexes and Applications in Lewis Acid Catalysis

    Koten, G. van; Meijer, M.D.; Ronde, N.; Vogt, D.; Klink, G.P.M. van

    2001-01-01

    Synthetic routes have been developed for the attachment of palladium(II) bis(amino)aryl (NCN or C6H2{CH2NMe2}2-2,6)- complexes to C60. Using diazo and Bingel addition reactions, various methanofullerene NCN-SiMe3 compounds (C60-L-NCN-SiMe3, L = C(Me), C(CO2Et)CO2CH2, and C(Me)C6H4CC) have been prepa

  1. Synthesis and antiproliferative activity of novel 2-aryl-4-benzoyl-imidazole derivatives targeting tubulin polymerization

    Chen, Jianjun; Li, Chien-Ming; Wang, Jin; Ahn, Sunjoo; Wang, Zhao; Lu, Yan; Dalton, James T.; Miller, Duane D.; Li, Wei

    2011-01-01

    We previously reported the discovery of 2-aryl-4-benzoyl-imidazoles (ABI-I) as potent antiproliferative agents for melanoma. To further understand the structural requirements for the potency of ABI analogs, gain insight in the structure-activity relationships (SAR), and investigate metabolic stability for these compounds, we report extensive SAR studies on the ABI-I scaffold. Compared with the previous set of ABI-I analogs, the newly synthesized ABI-II analogs have lower potency in general, b...

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

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

    2004-08-05

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

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

    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 basic...

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

    Moara T. da Silva

    2012-06-01

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

  5. Fragmentation Mechanism of Trans-α-Aryl-β-enamino Esters

    JIANG,Nan(蒋楠); WANG,Jian-Bo(王剑波); HE,Mei-Yu(何美玉)

    2002-01-01

    Electron impact-induced fragmentation mechanisms of trans-α-aryl-β-enamino esters were investigated using mass-analyzed ion kindetic energy (MIKE) spectrometry and high resolution accurate mass data. It was found that the main characteristic fragmentations of compounds studied were: an odd electron ion M+. - EtOH was formed by losing a neutral molecule of ethanol; and the skeletal rearrangements took place; and the ring opening reaction happened after losing a carbon monoxide;and the typical McLafferty rearrangement underwent in ester group. The cyclization reaction caused by losing neutral molecule of TsNH2 due to the ortho-effects of substituted group of aromatic ring was also observed.

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

    Li Chen

    2010-10-01

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

  7. Diphosphine dioxides as extractants for actinides (in connection with the problem of anomalous aryl strengthening of complexes)

    Extraction study of uranylnitrate, plutonium in trivalent, tetravalent and gexavalent states and trivalent americium, curium, praseodymium and promethium by alkyl, aromatic and mixed diphosphine dioxides is briefly outlined. The influence of diphosphine dioxide structures on their extraction capacity and, in particular, the problem of anomalous aryl strengthening of compounds, both of entropy and binding character, are considered. Perchlorate media, as opposed to nitrate ones, are characteristic for their high distribution coefficients and extraction equilibrium constants. Anomalous aryl strengthening of trivalent lanthanides and actinides can be applied, at the minimum, for solution purifications from the traces of actinides and lanthanides

  8. Synthesis of 1-aryl-3-(3,4-dihydro-2H-chromen-5-yl)ureas as TNF-α inhibitors

    2007-01-01

    A new series of compounds, 1-aryl-3-(3,4-dihydro-2H-chromen-5-yl) ureas, have been synthesized and their structures were confirmed by FAB-MS and 1H NMR. The preliminary pharmacological screening showed that these compounds inhibited TNF-αproduction in lipopolysaccharide (LPS)-stimulated THP-1 cells.

  9. Functionalization of 2H-1,2,3-Triazole C-Nucleoside Template via N(2) Selective Arylation.

    Lopes, Alexandra Basilio; Wagner, Patrick; de Souza, Rodrigo Octavio Mendonça Alves; Germain, Nadège Lubin; Uziel, Jacques; Bourguignon, Jean-Jacques; Schmitt, Martine; Miranda, Leandro S M

    2016-06-01

    C-Nucleosides are an underexplored and important class of nucleosides with antiviral and anticancer activity. In addition, triazole heterocycles are well employed as a strategy to modify nucleobase in nucleoside analogues, although rare examples were described for triazoyl C-nucleosides. N(2)-Aryl-1,2,3-triazole C-nucleoside compounds that could be obtained by selective 1,2,3-triazole heterocycle N(2) arylation in 1-β-d-ribofuranosyl-2H-1,2,3-triazole substrate were designed in this study. The optimized condition used AdBrettPhos/[PdCl(allyl)]2 as the catalyst system. This transformation was accomplished by aryl halides bearing an electron donor and withdrawing groups, as well as by heterocyclic halides in good to excellent yields. The transformation developed in this study represents a significant contribution to the nucleoside field, once it allows for the synthesis of unexplored scaffolds through selective functionalization of triazole nucleosides. PMID:27166644

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

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

    2015-07-01

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

  11. Synthesis and biological screening for cytotoxic activity of N-substituted indolines and morpholines.

    Doan, Phuong; Karjalainen, Anzhelika; Chandraseelan, Jerome G; Sandberg, Ossi; Yli-Harja, Olli; Rosholm, Tomi; Franzen, Robert; Candeias, Nuno R; Kandhavelu, Meenakshisundaram

    2016-09-14

    Development of novel anticancer drugs is inevitable to improve treatment of cancers. In this study, novel derivatives of indoline and morpholine were synthesized and tested for their cytotoxic effects on osteosarcoma and Human Embryonic Kidney cells. To characterize cytotoxicity and the mechanism of cell death, we used cytotoxicity, migration, apoptosis markers and mitochondrial calcium assays. Among the compounds tested, the indoline derivatives, generally, produced a higher cytotoxic effect compared to the morpholine derivatives, in osteosarcoma cells. Specifically, new indoline derivative N-(2-hydroxy-5-nitrophenyl(4'-methylphenyl)methyl)indoline exhibited effective cytotoxic activity, with an IC50 of ∼74 μM. The same molecule induced cell death by apoptosis and inhibited migration of the cells. Further, analysis of mitochondrial calcium levels revealed the existence of calcium dependent cell death mechanisms in different cell types. Therefore, N-(2-hydroxy-5-nitrophenyl(4'-methylphenyl)methyl)indoline can be considered as a potential drug-lead compound towards the discovery of new anti-cancer agents. PMID:27214140

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

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

    2009-12-15

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

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

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

    2016-01-18

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

  14. Cavity ring-down spectroscopy of the 6ν3 bands of 15N substituted N2O

    The 6ν3 and ν2+6ν3-ν2 bands of 15N substituted nitrous oxide isotopologues have been recorded by a continuous-wave cavity ring-down spectrometer (CW-CRDS) operated near 0.8μm. 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 6ν3 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.

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

    Grossmann, Arlett

    2012-07-03

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

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

    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.

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

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

    2010-04-09

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

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

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

    2015-08-01

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

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

    Yang Chen; Hui Xu

    2007-01-01

    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.

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

    Yang Chen

    2007-04-01

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

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

    Rahman Hosseinzadeh; Mahmood Tajbakhsh; Maryam Mohadjerani; Mohammad Alikarami

    2010-03-01

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

  2. Synthesis, characterization and antiproliferative activity of β-aryl-δ-iodo-γ-lactones

    Wzorek, Alicja; Gawdzik, Barbara; Gładkowski, Witold; Urbaniak, Mariusz; Barańska, Anita; Malińska, Maura; Woźniak, Krzysztof; Kempińska, Katarzyna; Wietrzyk, Joanna

    2013-09-01

    A convenient pathway for the synthesis of new of β-aryl-δ-iodo-γ-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.

  3. Fluoroalkylation of aryl ether perfluorocyclobutyl polymers

    Ligon, Clark; Ameduri, Bruno; Boutevin, Bernard; Smith, Dennis

    2008-01-01

    Post functionalization of aryl ether perfluorocyclobutyl (PFCB) polymers with fluoroalkyl side chains was accomplished with Umemoto's FITS reagents. The fluoroalkylated PFCB polymers (20 % functionalized) showed increases in both hydrophobicity and oleophobicity. Static contact angle for hexadecane was increased after fluoroalkylation from 0° to greater than 30° for the two PFCB polymers tested. Increased oil repellency makes these materials potential candidates for various coatings applicati...

  4. 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

    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 μg/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.

  5. Palladium-Catalyzed Arylation of Fluoroalkylamines

    Brusoe, Andrew T.; Hartwig, John F.

    2015-01-01

    We report the synthesis of fluorinated anilines by palladium-catalyzed coupling of fluoroalkylamines with aryl bromides and aryl chlorides. The products of these reactions are valuable because anilines typically require the presence of an electron-withdrawing substituent on nitrogen to suppress aerobic or metabolic oxidation, and the fluoroalkyl groups have steric properties and polarity distinct from those of more common electron-withdrawing amide and sulfonamide units. The fluoroalkylaniline products are unstable under typical conditions for C–N coupling reactions (heat and strong base). However, the reactions conducted with the weaker base KOPh, which has rarely been used in cross-coupling to form C–N bonds, occurred in high yield in the presence of a catalyst derived from commercially available AdBippyPhos and [Pd(allyl)Cl]2. Under these conditions, the reactions occur with low catalyst loadings (<0.50 mol % for most substrates) and tolerate the presence of various functional groups that react with the strong bases that are typically used in Pd-catalyzed C–N cross-coupling reactions of aryl halides. The resting state of the catalyst is the phenoxide complex, (BippyPhosPd(Ar)OPh); due to the electron-withdrawing property of the fluoroalkyl substituent, the turnover-limiting step of the reaction is reductive elimination to form the C–N bond. PMID:26065341

  6. Palladium-Catalyzed alpha-Arylation of Tetramic Acids

    Storgaard, Morten; Dorwald, F. Z.; Peschke, B.;

    2009-01-01

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

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

    Caccia, Silvio

    2007-08-01

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

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

    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.

  9. Ferric chloride-catalyzed reaction of [60]fullerene with tert-butyl N-substituted carbamates: synthesis of oxazolidino[4,5:1,2][60]fullerenes.

    You, Xun; Wang, Guan-Wu

    2014-01-01

    The rare oxazolidinofullerenes have been prepared by the ferric chloride-catalyzed reaction of [60]fullerene with various tert-butyl N-substituted carbamates via t-Bu-O bond cleavage and heteroannulation under mild conditions. A possible mechanism for the formation of oxazolidinofullerenes is proposed. PMID:24328055

  10. Palladium-catalyzed cross-coupling reactions of aryl boronic acids with aryl halides in water.

    Wang, Shaoyan; Zhang, Zhiqiang; Hu, Zhizhi; Wang, Yue; Lei, Peng; Chi, Haijun

    2009-01-01

    An efficient Suzuki cross-coupling reaction using a variety of aryl halides in neat water was developed. The Pd-catalyzed reaction between aryl bromides or chlorides and phenyl boronic acids was compatible with various functional groups and affords biphenyls in good to excellent yields without requirement of organic cosolvents. The air stability and solubility in water of the palladium-phosphinous acid complexes were considered to facilitate operation of the coupling reaction and product isolation. The reaction conditions including Pd catalyst selection, temperature, base and catalyst recoverability were also investigated. PMID:25084408

  11. A THEORETICAL EVALUATION OF ELECTROCONDUCTIVE PROPERTIES FOR [1,2,4]-TRIAZOLE 4N-SUBSTITUTED POLYMERS

    Adolfo E. Ensuncho

    2015-05-01

    Full Text Available In order to evaluate a set of electrical and optical properties by using time-dependent density functional theory (TD-DFT, at level of theory B3LYP/6-31G(d, the 4N-substituted [1,2,4]-Triazole (TAZ oligomers and substituted derivatives were studied using cyano, amino, methyl and fluoro functional groups. Additionally, specific properties were theoretically evaluated, namely electronic and geometrical properties, excitation energies, λmax, and the HOMO-LUMO orbital of the different oligomers TAZ with repeated units of 4 to 20 rings. These properties were extrapolated to polymer by using a second order polynomial fit. The oligomers studied exhibited a high molecular planarity, favoring electronic delocalization. Thus, an increase of the monomeric units in the different TAZ oligomers and their corresponding substituents led to an improvement in these properties, showing the best results for the cyano group. The findings contribute to the design of charge carrier polymeric materials and photoluminescent devices (OLEDs.

  12. Utility of N-aryl 2-aroylhydrazono-propanehydrazonoyl chlorides as precursors for synthesis of new functionalized 1,3,4-thiadiazoles with potential antimicrobial activity

    Abdou O. Abdelhamid

    2015-11-01

    Full Text Available Starting from N-aryl 2-aroylhydrazono-propanehydrazonoyl chlorides, a series of new functionalized 1,3,4-thiadiazoles were prepared. The structures of the compounds prepared were confirmed by both elemental and spectral analyses as well as by alternate synthesis. The mechanisms of the studied reactions are outlined. The antimicrobial activities of the compounds prepared were screened and the results showed that most of such compounds exhibit considerable activities.

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

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

  14. Selective copper catalysed aromatic N-arylation in water

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

    2013-01-01

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

  15. A New Route to Azafluoranthene Natural Products via Direct Arylation

    Ponnala, Shashikanth; Harding, Wayne W.

    2013-01-01

    Microwave-assisted direct arylation was successfully employed in the synthesis of azafluoranthene alkaloids for the first time. Direct arylation reactions on a diverse set of phenyltetrahydroisoquinolines produces the indeno[1,2,3-ij]isoquinoline nucleus en route to a high yielding azafluoranthene synthesis.

  16. Synthesis and biological evaluation of some new N4-aryl substituted 5-chloroisatin-3-thiosemicarbazones.

    Pervez, Humayun; Ramzan, Muhammad; Yaqub, Muhammad; Nasim, Faiz-ul-Hassan; Khan, Khalid Mohammed

    2012-05-01

    A new series of sixteen N4-aryl substituted 5-chloroisatin-3-thiosemicarbazones 2a-2p has been synthesized, characterized and tested for selected biological activities i.e. cytotoxicity, phytotoxicity and urease inhibition. In the brine shrimp bioassay, all the synthesized compounds gave LD50 values>2.30x10(-4) M-2.79x10(-4) M and were, therefore, found to be almost inactive, whereas in phytotoxicity assay, regardless of the nature of aryl substituents, they displayed weak to moderate (5-40%) phytotoxic activity at the highest tested concentrations (500 or 1000 μg/mL). In urease inhibition bioassay, compounds 2a, 2c, 2e, 2f, 2k and 2m exhibited relatively a higher degree of urease inhibition with IC50 values ranging from 38.91 μM to 76.65 μM and thus proved to be potent inhibitors of the enzyme. Of these, 2f and 2m displayed pronounced inhibition with IC50 values 38.91 μM and 39.50 μM, respectively, and may act as lead compounds for further studies. Structure-activity relationship (SAR) studies revealed that electronic effects of the substituents about the phenyl ring at N4 of the thiosemicarbazone moiety played an important role in enhancing the urease inhibitory potential of some of the synthesized compounds. PMID:22530899

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

    Juana Andrea Ibacache

    2014-01-01

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

  18. Facile synthesis and herbicidal evaluation of 2-aryl-4h-3, 1-benzoxazin-4-ones

    The present work deals with the synthesis of 4H-3,1-benzoxazin-4-ones carrying an aryl functional group at position-2. Synthesized compounds tested for herbicidal activity at three different doses (500 micro g/mL, 50 micro g/mL and 5 micro g/mL). Most of the compounds exhibited significant herbicidal activity against Lemna aequinocitalis welv at higher dose (500 micro g/mL). Among the tested compounds 2-phenyl-4H-3,1-benzoxazin-4-one (3a) and 2-(3-chlorophenyl)-4H-3,1-benzoxazin-4-one (3l) completely inhibited the plant growth at 500 and 50 micro g/mL concentrations. All the synthetic compounds were characterized by FT-IR, 1H NMR, EI-MS and elemental analysis. (author)

  19. Recombinant expression of the Aryl Hydrocarbon Receptor

    Shaikh-Omar, Osama

    2007-01-01

    Aryl Hydrocarbon Receptor (AhR) mediates drug and toxin action. The AhR proteins have been characterised in several mammalian species, and are soluble proteins found in various tissues. The AhR is normally found in the cytoplasm in a complex with 90 KDa heat shock protein (hsp90) and cellular chaperones such as ARA9 (AIP or XAP2) and p23. However, there has not been a systematic analysis of the proteins which chaperone the AhR ligand-binding domain (LBD). This work investigates the interactio...

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

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

    2012-12-01

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

  1. MICROWAVE ASSISTED SYNTHESIS AND BIOLOGICAL EVALUATION OF 2-ARYL/HETERYL-3-ARYLOXY/HETERYLOXY-4H-CHROMONES (4-OXO-2-ARYL/HETERYL-4H-CHROMEN-3-Yl-CARBOXYLATE

    Mangesh P. Gharpure

    2013-03-01

    Full Text Available 2-Aryl/heteryl-3-aryloxy/heteryloxy-4H-chromones 5 have been synthesized through a series of reactions starting from phenols under microwave irradiation. This process is an effective alternative to the traditional thermal heating method. The yields are excellent and the reaction time is in a few minutes. These compounds have been characterized on the basis of IR, 1H NMR, 13C NMR and Mass spectrometry and evaluated for antibacterial activity.

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

    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.

  3. Palladium-Catalyzed Ortho-Arylation of Carbamate-Protected Estrogens.

    Bedford, Robin B; Brenner, Peter B; Durrant, Steven J; Gallagher, Timothy; Méndez-Gálvez, Carolina; Montgomery, Michelle

    2016-05-01

    The palladium-catalyzed ortho-arylation of diethyl carbamate-protected estrone and estriol with aryl iodides gives the 2-arylated analogues. Subsequent removal of the carbamate directing group furnishes 2-arylated estrone, estradiol, or estriol depending on the method used. PMID:27057762

  4. Synthesis, structure, and spectroscopic properties of early transition metal eta/sup 2/-iminoacyl complexes containing aryl oxide ligation

    Chamberlain, L.R.; Durfee, L.D.; Fanwick, P.E.; Kobriger, L.; Latesky, S.L.; McMullen, A.K.; Rothwell, I.P.; Folting, K.; Huffman, J.C.; Streib, W.E.; Wang, R.

    1987-01-21

    The authors wish to report here a combination of synthetic, spectroscopic, and structural studies on a number of early transition metal aryl oxide compounds containing eta/sup 2/-iminoacyl ligands. This work has allowed us to isolate and study compounds containing more than one eta/sup 2/-iminoacyl function, a situation as yet unknown for their eta/sup 2/-acyl counterparts. Compounds such as these are of importance as they may give insights into the pathways whereby the observed intramolecular coupling (carbon-carbon double bond formation) of these types of ligand can take place to produce ene-diolate, enamidolate, or ene-diamide functional groups.

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

    Suresh S Patil; Swati D Jadhav; M B Deshmukh

    2012-09-01

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

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

    Yaowu Sha; Feng Wang; Ruogu Peng

    2007-01-01

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

  7. Factors influencing the in vitro activity of two new aryl-fluoroquinolone antimicrobial agents, difloxacin (A-56619) and A-56620.

    L Hirschhorn; Neu, H C

    1986-01-01

    The in vitro activity of difloxacin (A-56619) and A-56620, two new aryl-difluoroquinolones, was decreased by magnesium at 9 mM and in assay at pH 5.5 or in urine. Resistance was seen with members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus repeatedly exposed to subinhibitory concentrations of the compounds. The frequency of resistance was similar to that found for other new quinolones.

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

    Masoumeh Zakeri; Majid M Heravi; Ebrahim Abouzari-Lotf

    2013-07-01

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

  9. Palladium-Catalyzed Negishi Cross-Coupling Reaction of Aryl Halides with (Difluoromethyl)zinc Reagent.

    Aikawa, Kohsuke; Serizawa, Hiroki; Ishii, Koki; Mikami, Koichi

    2016-08-01

    The palladium-catalyzed Negishi cross-coupling reaction of aryl iodides and bromides with (difluoromethyl)zinc reagent bearing a diamine such as TMEDA is achieved to provide the difluoromethylated aromatic compounds in good to excellent yields. The advantages of (difluoromethyl)zinc reagent are that (1) the derivatives, which possess different stability and reactivity, can be readily prepared via ligand screening and (2) transmetalation of a difluoromethyl group from the zinc reagent to palladium catalyst efficiently proceeds without an activator. PMID:27442347

  10. Anthocyan does not suppress transformation of aryl hydrocarbon receptor induced by dioxin.

    Mukai, Rie; Fukuda, Itsuko; Nishiumi, Shin; Hosokawa, Keizo; Kanazawa, Kazuki; Ashida, Hitoshi

    2004-01-01

    Dioxins cause a variety of toxic effects through transformation of a cytosolic aryl hydrocarbon receptor (AhR). We have previously demonstrated that certain natural flavones and flavonols at the dietary levels suppress AhR transformation. In this study, we investigated whether 5 anthocyanidins, 15 anthocyanins, and protocatechuic acid suppress AhR transformation in mouse hepatoma Hepa-1c1c7 cells. All the compounds tested here at 5 microM unexpectedly failed to suppress the transformation induced by 0.1 nM TCDD, indicating that anthocyan does not have a potential to prevent dioxin toxicity. PMID:15630228

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

    Elnaz Karimian; Batool Akhlaghinia; Sara S E Ghodsinia

    2016-03-01

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

  12. Practical Direct α-Arylation of Cyclopentanones by Palladium/Enamine Cooperative Catalysis.

    Xu, Yan; Su, Tianshun; Huang, Zhongxing; Dong, Guangbin

    2016-02-12

    Direct arylation of cyclopentanones has been a long-standing challenge because of competitive self-aldol condensation and multiple arylations. Reported herein is a direct mono-α-C-H arylation of cyclopentanones with aryl bromides which is enabled by palladium/amine cooperative catalysis. This method is scalable and chemoselective with broad functional-group tolerance. Application to controlled sequential arylation of cyclopentanones has been also demonstrated. PMID:26840218

  13. Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants.

    Chakraborty, Kajal; Joseph, Deepu; Joy, Minju; Raola, Vamshi Krishna

    2016-12-01

    The ethyl acetate fraction of red seaweed Hypnea musciformis was purified to yield three substituted aryl meroterpenoids, namely, 2-(tetrahydro-5-(4-hydroxyphenyl)-4-pentylfuran-3-yl)-ethyl-4-hydroxybenzoate (1), 2-2-[(4-hydroxybenzoyl)-oxy]-ethyl-4-methoxy-4-2-[(4-methylpentyl)oxy]-3,4-dihydro-2H-6-pyranylbutanoic acid (2) and 3-((5-butyl-3-methyl-5,6-dihydro-2H-pyran-2-yl)-methyl)-4-methoxy-4-oxobutyl benzoate (3). The structures of these compounds, as well as their relative stereochemistries, were confirmed by exhaustive NMR spectroscopic data analyses. Compound 1 exhibited similar 2,2'-diphenylpicrylhydrazyl radical inhibiting and Fe(2+) ion chelating activities (IC50 25.05 and 350.7μM, respectively) as that of commercial antioxidant gallic acid (IC50 32.3 and 646.6μM, respectively), followed by 3 (IC50 231.2 and 667.9μM, respectively), and 2 (IC50 322.4 and 5115.3μM, respectively), in descending order of activities. Structure-activity relationship analysis revealed that the antioxidant activities of these compounds were directly proportional to the steric and hydrophobic parameters. The seaweed derived aryl meroterpenoids might serve as potential lead antioxidative molecules for use in pharmaceutical and food industries. PMID:27374595

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

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

    2015-08-24

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

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

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

    2010-05-01

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

  16. 3-Aryl beta-carbolin-1-ones as a new class of potent inhibitors of tumor cell proliferation: synthesis and biological evaluation.

    Wang, Shaozhong; Dong, Yanmei; Wang, Xinyan; Hu, Xiaoyi; Liu, Jun O; Hu, Yuefei

    2005-03-01

    A novel three-step synthesis of 3-aryl beta-carbolin-1-ones from non-indole starting materials has been developed. The two nitrogen atoms in beta-carbolin-1-one were introduced efficiently by Michael addition of ethyl acetamidocyanoacetate to chalcone. The desired pyridone and indole rings were assembled by an intramolecular ketone-nitrile annulation mediated by aqueous HCl-HOAc and a Cu(I)-catalyzed intramolecular N-arylation of the amide, respectively. The target compounds were found to possess significant activity against tumor cell proliferation. PMID:15731878

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

    Yang Dong-Dong

    2012-06-01

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

  18. Design, synthesis and biological assessment of novel N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines and 3-substituted 2,6-dioxopiperidines for TNF-α inhibitory activity.

    Luo, Weiming; Yu, Qian-sheng; Salcedo, Isidro; Holloway, Harold W; Lahiri, Debomoy K; Brossi, Arnold; Tweedie, David; Greig, Nigel H

    2011-07-01

    Eight novel 2-(2,6-dioxopiperidin-3-yl)phthalimidine EM-12 dithiocarbamates 9 and 10, N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines 11-14 and 3-substituted 2,6-dioxopiperidines 16 and 18 were synthesized as tumor necrosis factor-α (TNF-α) synthesis inhibitors. Synthesis involved utilization of a novel condensation approach, a one-pot reaction involving addition, iminium rearrangement and elimination, to generate the phthalimidine ring required for the creation of compounds 9-14. Agents were, thereafter, quantitatively assessed for their ability to suppress the synthesis on TNF-α in a lipopolysaccharide (LPS)-challenged mouse macrophage-like cellular screen, utilizing cultured RAW 264.7 cells. Whereas compounds 9, 14 and 16 exhibited potent TNF-α lowering activity, reducing TNF-α by up to 48% at 30 μM, compounds 12, 17 and 18 presented moderate TNF-α inhibitory action. The TNF-α lowering properties of these analogs proved more potent than that of revlimid (3) and thalidomide (1). In particular, N-dithiophthalimidomethyl-3-(phthalimidin-2-yl)-2,6-dioxopiperidine 14 not only possessed the greatest potency of the analogs to reduce TNF-α synthesis, but achieved this with minor cellular toxicity at 30 μM. The pharmacological focus of the presented compounds is towards the development of well-tolerated agents to ameliorate the neuroinflammation, that is, commonly associated with neurodegenerative disorders, epitomized by Alzheimer's disease and Parkinson's disease. PMID:21658960

  19. Thermal Decomposition of Dicyclopentadienyltitanium(IV) Diaryl and Dibenzyl Compounds

    Boekel, C.P.; Teuben, J.H.; Liefde Meijer, H.J. de

    1974-01-01

    The thermal decomposition of compounds of the type Cp2TiR2 (Cp = cyclopentadienyl, R = aryl or benzyl) in the solid state and in various solvents has been studied. In the solid state and in aromatic and aliphatic hydrocarbon solvents the compounds decompose with quantitative formation of R-H and a T

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

    Agarwal Alka

    2013-03-01

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

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

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

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

    Volodymyr V. Tkachenko

    2014-12-01

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

  3. 2-aminopyrimidine-4,6-diol as an efficient ligand for solvent-free copper-catalyzed N-arylations of imidazoles with aryl and heteroaryl halides.

    Xie, Ye-Xiang; Pi, Shao-Feng; Wang, Jian; Yin, Du-Lin; Li, Jin-Heng

    2006-10-13

    Efficient and solvent-free copper-catalyzed N-arylations of imidazoles with aryl and heteroaryl halides have been demonstrated. In the presence of CuBr, 2-aminopyrimidine-4,6-diol, and TBAF (n-Bu4NF), a variety of imidazoles underwent the N-arylation reaction with aryl and heteroaryl halides smoothly in moderate to excellent yields. Noteworthy is that the reaction is conducted under solvent-free conditions. PMID:17025338

  4. SYNTHESIS AND BIOLOGICAL ACTIVITIES OF DERIVATIVES OF 3-ARYL/ARYLOXYMETHYL-6-ARYL-1,2,4-TRIAZOLO[3,4-B]-1,3,4-THIADIAZOLES%3-芳基/芳氧甲基-6-芳基-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑衍生物的合成及生物活性

    史海健; 王忠义; 史好新

    1999-01-01

    AIM: To synthesize a number of novel heterocyclic compounds and screen for their biological activities. Sixteen title compounds were prepared. METHODS: These novel compounds were prepared by the reaction of 3-aryl/aryloxymethyl-4-amino-5-mercapto-1,2,4-triazoles with aryl carboxylic acids in the presence of phosphorus oxychloride. The structures of these compounds were confirmed by elemental analysis, IR, 1HNMR and MS. The reaction conditions for the synthesis had been investigated. All the compounds were screened for antimicrobial activity against bacteria S.aureus, E.coli and B.subilis. The concentration of the test compounds was 0.002%. The antibacterial activities of the test compounds were compared with those of penicillin and gentamicin. RESULTS: The results display that some of them possess strong biological activities.CONCLUSION: Syntheses of these novel heterocyclic compounds and study on their biological activities are very important and valuable in medicine.

  5. Azo-hydrazone tautomerism of aryl azo pyridone dyes

    Mirković Jelena M.

    2013-01-01

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

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

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

    2016-04-01

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

  7. Heck Arylation of Acrylonitrile with Aryl Iodides Catalyzed by a Silica-bound Arsine Palladium(0) Complex

    Ming Zhong CAI; Hong ZHAO; Rong Li ZHANG

    2005-01-01

    Acrylonitrile reacts with aryl iodides in the presence of tri-n-butylamine and a catalytic amount of a silica-bound arsine palladium(0) complex to afford stereoselectively (E)-cinnamonitriles in high yields.

  8. Synthesis and anticonvulsant activity of some potent 5,6-bis aryl 1,2,4-triazines

    MALLIKARJUNA B.P.; SURESH KUMAR G.V.; SASTRY B.S.; NAGARAJ; MANOHARA K.P.

    2007-01-01

    In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a~5f were synthesized by condensation of various benzils 4a~4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies.Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectroscopic data.

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

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

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

    Ashok D, Sudershan K,Khalilullah M

    2011-10-01

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

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

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

    2013-08-01

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

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

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

    2016-05-25

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

  13. Microwave-Promoted Rapid Synthesis of 1-Aryl-1, 2, 3-Triazoles

    2001-01-01

    Aryl azides and a-keto phosphorus ylides were reacted within 4~10 minutes with silica gel support, under microwave irridiation to afford corresponding l-aryl-l, 2, 3-triazoles in moderate to good yields.

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

    Mehmet Emin Topaloglu

    2011-06-01

    Full Text Available The development of resistance to current antifungal therapeutics drives the search for new effective agents. The fact that several acetophenone-derived Mannich bases had shown remarkable antifungal activities in our previous studies led us to design and synthesize some acetophenone-derived Mannich bases, 1-8 and 2-acetylthiophene-derived Mannich base 9, 1-aryl-2-dimethylaminomethyl-2-propen-1-one hydrochloride, to evaluate their antifungal activities. The designed chemical structures have α,β-unsaturated ketone moieties, which are responsible for the bioactivities of the Mannich bases. The aryl part was C6H5 (1; 4-CH3C6H4 (2; 4-CH3OC6H4 (3; 4-ClC6H4 (4; 4-FC6H4 (5; 4-BrC6H4 (6; 4-HOC6H4 (7; 4-NO2C6H4 (8; and C4H3S(2-yl (9. In this study the designed compounds were synthesized by the conventional heating method and also by the microwave irradiation method to compare these methods in terms of reaction times and yields to find an optimum synthetic method, which can be applied for the synthesis of Mannich bases in further studies. Since there are limited number of studies reporting the synthesis of Mannich bases by microwave irradiation, this study may also contribute to the general literature on Mannich bases. Compound 7 was reported for the first time. Antifungal activities of all compounds and synthesis of the compounds by microwave irradiation were also reported for the first time by this study. Fungi (15 species were used for antifungal activity test. Amphotericin B was tested as an antifungal reference compound. In conclusion, compounds 1-6, and 9, which had more potent (2–16 times antifungal activity than the reference compound amphotericin B against some fungi, can be model compounds for further studies to develop new antifungal agents. In addition, microwave irradiation can be considered to reduce reaction period, while the conventional method can still be considered to obtain compounds with higher reaction yields in the synthesis of

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

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

    2016-05-01

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

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

    Deshpande, Shreenivas R.; Pai, K. Vasantakumar

    2010-01-01

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

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

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

    2015-01-01

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

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

    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.

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

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

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

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

    2010-01-15

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

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

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

    1980-10-01

    For treatment of chronic iron overload (as occurs in Cooley's anemia), ferric ion sequestering agents with specific properties are necessary. Two analogues of enterobactin [a microbial chelating agent with the greatest stability constant known for an Fe(III) complex] are reported which exhibit: i) hydrolytic stability; ii) water solubility; iii) N-substitution to block peptidase hydrolysis. The first compound, N,N',N"- trimethyl-N,N',N"-tris(2,3-dihydroxysulfobenzoyl)1,3,5-triaminomethyl- benzene, [Me{sub 3}MECAMS, 6] was prepared from the amide of trimesloyl chloride (1) and MeNH{sub 2}. The resulting amide was reduced to the triamine (3) and converted in three steps to the final product 6 in 6% overall yield. The proton-dependent formation constant (log K*) for the reaction: Fe{sup 3+} + H{sub 3}L{sup 6-} = FeL{sup 6-} + 3H{sup +} is 4.87, which gives an equilibrium concentration of [Fe{sup 3+}] at pH 7.4 of 2 x 10{sup -27} M for 10{sup -5} M L (6) and 10{sup -6} M total Fe{sup 3+}. The estimated formation constant (log {beta}{sub 110}) is 40. At low pH the FeL{sup 6-} complex undergoes a series of three, one-proton reactions which probably gives a tris-salicylate complex formed by the carbonyl and ortho-catechol oxygen of the 2,3~dihydroxybenzoyl units (the same reaction that occurs with ferric enterobactin). After six hours in the presence of 6 mM ascorbate, Me{sub 3}MECAMS (6.0 mM) removed 3.7% of the ferric ion initially sequestered by the iron storage protein, ferritin. The human iron transport protein transferrin goves up iron to Me{sub 3}MECAMS with a pseudo first-order rate constant of 1.9 x 10{sup -3}min{sup -1} (ligand concentration 2 X 10{sup -4} M). This rate is comparable to that of enterobactin and other catechoyl amide sequestering agents. and greatly exceeds that of desferrioxamine B (Desferal{reg-sign}). the current drug of choice in treating iron overload. Two related compounds have been prepared in which the catechol ring is

  2. Opioids and Efflux Transporters. 1. P-Glycoprotein Substrate Activity of N-Substituted Analogs of Meperidine.

    Mercer, Susan L.; Cunningham, Christopher W.; Hassan, Hazem; Eddington, Natalie D.; Coop, Andrew

    2006-01-01

    P-Glycoprotein (P-gp) is an efflux transporter which is up-regulated at the blood brain barrier in both morphine and oxycodone tolerant rats. Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-gp, suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of compounds, and show that a meperidine anal...

  3. Chan-Evans-Lam Amination of Boronic Acid Pinacol (BPin) Esters: Overcoming the Aryl Amine Problem.

    Vantourout, Julien C; Law, Robert P; Isidro-Llobet, Albert; Atkinson, Stephen J; Watson, Allan J B

    2016-05-01

    The Chan-Evans-Lam reaction is a valuable C-N bond forming process. However, aryl boronic acid pinacol (BPin) ester reagents can be difficult coupling partners that often deliver low yields, in particular in reactions with aryl amines. Herein, we report effective reaction conditions for the Chan-Evans-Lam amination of aryl BPin with alkyl and aryl amines. A mixed MeCN/EtOH solvent system was found to enable effective C-N bond formation using aryl amines while EtOH is not required for the coupling of alkyl amines. PMID:27045570

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

    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

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

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

    2012-01-01

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

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

    Nilotpal Barooah; Chandan Tamuly; Jubaraj B Baruah

    2005-03-01

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

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

    Brajesh Kumar; Kumari Smita; Brajendra Kumar; Luis Cumbal

    2014-11-01

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

  8. Aminocatalysis-Mediated on-Resin Ugi Reactions: Application in the Solid-Phase Synthesis of N-Substituted and Tetrazolo Lipopeptides and Peptidosteroids.

    Morales, Fidel E; Garay, Hilda E; Muñoz, Daniela F; Augusto, Yarelys E; Otero-González, Anselmo J; Reyes Acosta, Osvaldo; Rivera, Daniel G

    2015-06-01

    A new solid-phase protocol for the synthesis of N-substituted and tetrazolo peptides is described. The strategy relies on the combination of aminocatalysis-mediated on-resin Ugi reactions and peptide couplings for the N-alkylation of peptides at selected sites, including the N-terminal double lipidation, the simultaneous lipidation/biotinylation, and the steroid/lipid conjugation via tetrazole ring formation. The solid-phase Ugi four-component reactions were enabled by on-resin transimination steps prior to addition of the acid and isocyanide components. The strategy proved to be suitable for the feasible incorporation of complex N-substituents at both termini and at internal positions, which is not easily achievable by other solid-phase methods. PMID:25994574

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

    Rajendra Surasani

    2012-11-01

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

  10. Synthesis, Biological Evaluation and Molecular Docking Studies of 6-Aryl-2-Styrylquinazolin-4(3H)-Ones

    Emmanuel Ndubuisi Agbo; Tshepiso Jan Makhafola; Yee Siew Choong; Malose Jack Mphahlele; Ponnadurai Ramasami

    2015-01-01

    Suzuki-Miyaura cross-coupling of 6-bromo-2-styrylquinazolin-4(3H)-ones with arylboronic acids afforded a series of novel 6-aryl-2-styrylquinazolin-4(3H)-ones. These compounds were evaluated for potential anticancer properties against the human renal (TK-10), melanoma (UACC-62) and breast cancer (MCF-7) cell lines. Their antimicrobial properties were also evaluated against six Gram-positive and four Gram-negative bacteria, as well as two strains of fungi. Molecular docking studies (in silico) ...

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

    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.

  12. New Trends in Aryl Hydrocarbon Receptor Biology

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

    2016-01-01

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

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

    Jimit S. Patel

    2012-06-01

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

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

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

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

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

    1996-12-31

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

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

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

    2010-02-01

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

  17. Aryl-1,3,5-triazine derivatives as histamine H4 receptor ligands.

    Łażewska, Dorota; Więcek, Małgorzata; Ner, Joanna; Kamińska, Katarzyna; Kottke, Tim; Schwed, J Stephan; Zygmunt, Małgorzata; Karcz, Tadeusz; Olejarz, Agnieszka; Kuder, Kamil; Latacz, Gniewomir; Grosicki, Marek; Sapa, Jacek; Karolak-Wojciechowska, Janina; Stark, Holger; Kieć-Kononowicz, Katarzyna

    2014-08-18

    A series of novel 2-amino-4-(4-methylpiperazin-1-yl)-1,3,5-triazine derivatives with different aryl substituents in the 6-position was designed, synthesized and evaluated for histamine H4 receptor (H4R) affinity in Sf9 cells expressing human H4R co-expressed with G-protein subunits. Triazine derivative 8 with a 6-(p-chlorophenyl) substituent showed the highest affinity with hH4R Ki value of 203 nM and was classified as an antagonist in cAMP accumulation assay. This compound, identified as a new lead structure, demonstrated also anti-inflammatory properties in preliminary studies in mice (carrageenan-induced edema test) and neither possessed significant antiproliferative activity, nor modulated CYP3A4 activity up to concentration of 25 μM. In order to discuss structure-activity relationships molecular modeling and docking studies were undertaken. PMID:24996140

  18. Methanofullerene-Based Palladium Bis(amino)aryl Complexes and Applications in Lewis Acid Catalysis

    van Koten, G.; Meijer, M.D.; Ronde, N.; Vogt, D.; van Klink, G.P.M.

    2001-01-01

    Synthetic routes have been developed for the attachment of palladium(II) bis(amino)aryl (NCN or C6H2{CH2NMe2}2-2,6)- complexes to C60. Using diazo and Bingel addition reactions, various methanofullerene NCN-SiMe3 compounds (C60-L-NCN-SiMe3, L = C(Me), C(CO2Et)CO2CH2, and C(Me)C6H4CC) have been prepared and characterized. Electrophilic palladation of these ligands was achieved with Pd(OAc)2, leading to the corresponding C60-L-NCN·PdCl complexes. These were converted into active Lewis acid cata...

  19. Design, synthesis and biological evaluation of new aryl thiosemicarbazone as antichagasic candidates.

    Blau, Lorena; Menegon, Renato Farina; Trossini, Gustavo H G; Molino, João Vitor Dutra; Vital, Drielli Gomes; Cicarelli, Regina Maria Barretto; Passerini, Gabriela Duó; Bosquesi, Priscila Longhin; Chin, Chung Man

    2013-09-01

    The present work reports on the synthesis, biological assaying and docking studies of a series of 12 aryl thiosemicarbazones, which were planned to act over two main enzymes, cruzain and trypanothione reductase. These enzymes are used as targets of trypanocidal activity in Chagas disease control with a minimal mutagenic profile. Three p-nitroaromatic thiosemicarbazones showed high activity against Trypanosoma cruzi in in vitro assays (IC50 < 57 μM), and no mutagenic profile was observed in micronucleous tests. Although the in vitro inhibition test showed that 10-μM doses of eight compounds inhibited cruzain activity, no correlation was found between cruzain inhibition and trypanocidal activity. PMID:23851115

  20. Alkyl Aryl Ether Bond Formation with PhenoFluor**

    Shen, Xiao; Neumann, Constanze N.; Kleinlein, Claudia; Claudia, Nathaniel W.; Ritter, Tobias

    2015-01-01

    An alkyl aryl ether bond formation reaction between phenols and primary and secondary alcohols with PhenoFluor has been developed. The reaction features a broad substrate scope and tolerates many functional groups, and substrates that are challenging for more conventional ether bond forming processes may be coupled. A preliminary mechanistic study indicates reactivity distinct from conventional ether bond formation.

  1. Palladium-catalyzed arylation of simple arenes with iodonium salts.

    Storr, Thomas E; Greaney, Michael F

    2013-03-15

    The development of an arylation protocol for simple arenes with diaryliodonium salts using the Herrmann-Beller palladacycle catalyst is reported. The reaction takes simple aromatic feedstocks and creates valuable biaryls for use in all sectors of the chemical industry. PMID:23461706

  2. Kinetic Resolution of Aryl Alkenylcarbinols Catalyzed by Fc-PIP

    胡斌; 孟萌; 姜山山; 邓卫平

    2012-01-01

    An effective kinetic resolution of a variety of aryl alkenylcarbinols catalyzed by nonenzymatic acyl transfer catalyst Fe-PIP was developed, affording corresponding unreacted alcohols in good to excellent ee value up to 99% and with selectivity factors up to 24.

  3. Synthesis, antiviral activity and structure-activity relationship of 1-(1-aryl-4,5-dihydro-1H-imidazoline)-3-chlorosulfonylureas and products of their cyclization.

    Rządkowska, Marzena; Szacoń, Elżbieta; Kaczor, Agnieszka A; Rajtar, Barbara; Świątek, Łukasz; Polz-Dacewicz, Małgorzata; Matosiuk, Dariusz

    2016-10-01

    Novel 1-(1-aryl-4,5dihydro-1H-imidazoline)-3-chlorosulfonylourea derivatives 3a-3f were synthesized in the reaction of 1-aryl-4,5-dihydro-1H-imidazol-2-amines with chlorosulfonyl isocyanate. The second series of compounds 4a-4f was prepared from the respective 1-(1-aryl-4,5-dihydro-1H-imidazoline)-3-chlorsulfonylureas 3a-3f and 1,1'-carbonyldiimidazole (CDI). The selected compounds were tested for their activity against Herpes simplex virus and coxsackievirus B3 (CVB3). It was determined that three derivatives, i.e 3d, 4a and 4d are active against Herpes simplex virus (HSV-1). Compounds 3d and 4c are active against CVB3. Their favorable activity can be primarily attributed to their low lipophilicity values. Moreover, the lack of substituent in the phenyl moiety or 4-methoxy substitution can be considered as the most beneficial for the antiviral activity. PMID:26212601

  4. Characterization of natural aryl hydrocarbon receptor agonists from cassia seed and rosemary.

    Amakura, Yoshiaki; Yoshimura, Morio; Takaoka, Masashi; Toda, Haruka; Tsutsumi, Tomoaki; Matsuda, Rieko; Teshima, Reiko; Nakamura, Masafumi; Handa, Hiroshi; Yoshida, Takashi

    2014-01-01

    Many recent studies have suggested that activation of the aryl hydrocarbon receptor (AhR) reduces immune responses, thus suppressing allergies and autoimmune diseases. In our continuing study on natural AhR agonists in foods, we examined the influence of 37 health food materials on the AhR using a reporter gene assay, and found that aqueous ethanol extracts of cassia seed and rosemary had particularly high AhR activity. To characterize the AhR-activating substances in these samples, the chemical constituents of the respective extracts were identified. From an active ethyl acetate fraction of the cassia seed extract, eight aromatic compounds were isolated. Among these compounds, aurantio-obtusin, an anthraquinone, elicited marked AhR activation. Chromatographic separation of an active ethyl acetate fraction of the rosemary extract gave nine compounds. Among these compounds, cirsimaritin induced AhR activity at 10-10² μM, and nepitrin and homoplantagenin, which are flavone glucosides, showed marked AhR activation at 10-10³ μM. PMID:24747651

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

    Yoshiaki Amakura

    2014-04-01

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

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

    Muhammad Yaqub

    2011-07-01

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

  7. Synthesis, Biological Evaluation and Molecular Docking Studies of 6-Aryl-2-Styrylquinazolin-4(3H-Ones

    Emmanuel Ndubuisi Agbo

    2015-12-01

    Full Text Available Suzuki-Miyaura cross-coupling of 6-bromo-2-styrylquinazolin-4(3H-ones with arylboronic acids afforded a series of novel 6-aryl-2-styrylquinazolin-4(3H-ones. These compounds were evaluated for potential anticancer properties against the human renal (TK-10, melanoma (UACC-62 and breast cancer (MCF-7 cell lines. Their antimicrobial properties were also evaluated against six Gram-positive and four Gram-negative bacteria, as well as two strains of fungi. Molecular docking studies (in silico were conducted on compounds 5a, b, d and 6a, b, d–f to recognize the hypothetical binding motif of the title compounds within the active site of the dihydrofolate reductase and thymidylate synthase enzymes.

  8. Synthesis and bioactivity of 10 N-substituted amino coumarins%10种N-取代氨基香豆素的合成及生物活性

    张学良; 魏艳; 韦能春; 郝双红

    2013-01-01

    Under the guidance of substructure combination strategy, 10 iV-substituted amino coumarins were synthesized,their fungicidal and herbicidal activity was determined as well. 6-amino coumarin was prepared from reducing of 6-nitro coumarin by Fe/NH4Cl and condensed with different aldehyde to give the intermediate Schiff base,which was then reduced by sodium borohydride to give N-substituted amino coumarins. Nine of the compounds were not reported in the literature. The structures of the synthesized compounds were confirmed by IR,1H NMR and ESI-MS. All the synthesized compounds showed certain inhibition against Valsa mali, Coniothyrium diplodiella, Fusarium oxysporium and Citrusanthrax bacteria. Compound 4e indicated the most fungicidal activity with EC50 value of 7. 53 and 12. 93 mg/L against V. Mali and C. Bacteria respectively, and < 25 mg/L against the other 2 pathogens. The less antifungal compound was 4f with EC50 value of about 11 mg/L against V. Mali and C. Diplodiella. Furthermore, all the synthesized compounds except 4f have some herbicidal activity against the root and seedling development of Amaranthus retroflexus. The inhibitory rates of compound 4c against A . Retroflexus were 99% at 100 mg/L.%基于结构拼接思想,设计合成了10个N-取代氨基香豆素类化合物,并测定了其抑菌及除草活性.6-硝基香豆素经Fe/NH4Cl还原得6-氨基香豆素,再与不同醛缩合得Schiff碱,最后经硼氢化钠还原制得10个N-取代氨基香豆素类化合物(4a ~4J),其中9个未见文献报道,其结构均经红外光谱、核磁共振氢谱和质谱确认.抑菌活性测试结果表明,所有化合物对苹果腐烂病菌Valsamali、葡萄白腐病菌Coniothyrium diplodiella、棉花枯萎病菌Fusarium oxysporium和柑橘炭疽病菌Citrusanthrax bacteria均有一定抑制作用,其中4e的抑菌活性最强,对苹果腐烂病菌和柑橘炭疽病菌的EC50值分别为7.53和12.93 mg/L,对其余2种植物病原菌的EC50值均小于25 mg

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

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

    2012-01-01

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

  10. Synthesis, crystal Structures and aggregation-induced emission enhancement of aryl-substituted cyclopentadiene derivatives

    Zhang, Xiangdong [State Key Laboratory of Fine Chemicals and School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116012 (China); State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000 (China); Ye, Junwei, E-mail: junweiye@dlut.edu.cn [State Key Laboratory of Fine Chemicals and School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116012 (China); Xu, Lifeng; Yang, Lijian; Deng, Dai [State Key Laboratory of Fine Chemicals and School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116012 (China); Ning, Guiling, E-mail: ninggl@dlut.edu.cn [State Key Laboratory of Fine Chemicals and School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116012 (China)

    2013-07-15

    A series of cyclopentadiene derivates, namely, 1,2,4-triphenylcyclopenta-1,3-diene (1), 1,2-diphenyl-4-(p-methoxyphenyl)cyclopenta-1,3-diene (2) and 1,2-di(p-methoxyphenyl)-4-phenylcyclopenta-1,3-diene (3), were synthesized and their photoluminescence properties in solutions and aggregation state were investigated. Different photoluminescence properties of 1–3 were tuned by changing types and replace position of substituent groups. These cyclopentadiene derivates display solvent-dependent fluorescence emissions and typical aggregation-induced emission enhancement (AIEE) characteristics. The crystal structure analysis reveals that intermolecular C–H…π interactions and X-aggregation molecule stacking have a dramatic effect on the photoluminescent properties of 1–3. Additionally, the DFT calculations of these compounds were investigated. -- Graphical abstract: A series of aryl-substituted cyclopentadiene derivatives with AIEE properties were synthesized and their crystal structures and photoluminescence properties in solution and aggregation state were studied. Highlights: ► A series of cyclopentadiene derivates were synthesized via aldol condensation followed cyclizing and dehydrating reaction. ► The effect of solvents on fluorescence properties of these compounds were investigated in seven organic solvents. ► These compounds show typical aggregation-induced emission enhancement properties.

  11. Synthesis, crystal Structures and aggregation-induced emission enhancement of aryl-substituted cyclopentadiene derivatives

    A series of cyclopentadiene derivates, namely, 1,2,4-triphenylcyclopenta-1,3-diene (1), 1,2-diphenyl-4-(p-methoxyphenyl)cyclopenta-1,3-diene (2) and 1,2-di(p-methoxyphenyl)-4-phenylcyclopenta-1,3-diene (3), were synthesized and their photoluminescence properties in solutions and aggregation state were investigated. Different photoluminescence properties of 1–3 were tuned by changing types and replace position of substituent groups. These cyclopentadiene derivates display solvent-dependent fluorescence emissions and typical aggregation-induced emission enhancement (AIEE) characteristics. The crystal structure analysis reveals that intermolecular C–H…π interactions and X-aggregation molecule stacking have a dramatic effect on the photoluminescent properties of 1–3. Additionally, the DFT calculations of these compounds were investigated. -- Graphical abstract: A series of aryl-substituted cyclopentadiene derivatives with AIEE properties were synthesized and their crystal structures and photoluminescence properties in solution and aggregation state were studied. Highlights: ► A series of cyclopentadiene derivates were synthesized via aldol condensation followed cyclizing and dehydrating reaction. ► The effect of solvents on fluorescence properties of these compounds were investigated in seven organic solvents. ► These compounds show typical aggregation-induced emission enhancement properties

  12. Impregnated palladium on magnetite as catalyst for direct arylation of heterocycles

    Cano Monserrat, Rafael; Pérez Galera, Juana María; Ramón Dangla, Diego José; McGlacken, Gerard P.

    2016-01-01

    Palladium impregnated on magnetite is an efficient, cheap and easy to prepare catalyst for the direct arylation of heterocycles. Good yields are afforded under relatively mild conditions and a broad substrate scope is evident. The catalyst is regioselective in many cases, affording arylated products, at the C2- or C3-position (depending of the heterocycle used). The methodology can be extended to prepare chromenes through an intramolecular direct arylation reaction. Some evidence is provided ...

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

    Liu, Ning; Wang, Zhong-Xia

    2011-12-16

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

  14. Binding of polychlorinated biphenyls to the aryl hydrocarbon receptor.

    Kafafi, S A; Afeefy, H Y; A. H. Ali; Said, H K; Kafafi, A G

    1993-01-01

    A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that ...

  15. The electrochemistry of arylated anthraquinones in room temperature ionic liquids

    Gomis Berenguer, Alicia; Gómez Mingot, María; García Cruz, Leticia; Thiemann, Thies; Banks, Craig E.; Montiel Leguey, Vicente; Iniesta Valcárcel, Jesús

    2013-01-01

    Arylated anthraquinone derivatives of different sizes and different π-basicities have been prepared, and the electrochemical behaviour of these substances has been studied on screen printed graphite electrodes in the three room temperature ionic liquids (RTILs), 1-butyl-3-methylimidazolium hexafluorophosphate ([C4MIM][PF6]), 1-hexyl-3-methylimidazolium hexafluorophosphate ([C6MIM][PF6]) and 1-octyl-3-methylimidazolium hexafluorophosphate ([C8MIM][PF6]). Half redox potentials for the first and...

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

    Deshpande, Shreenivas R; Pai, K Vasantakumar

    2010-06-01

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

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

    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......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...

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

    Ramin Rezaei; Mohammadi, Mohammad K; Tahereh Ranjbar

    2011-01-01

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

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

    Ramaiyan Manikannan; Masilamani Shanmugaraja; Seetharaman Manojveer; Shanmugam Muthusubramanian

    2012-03-01

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

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

    Maria Gdaniec

    2010-02-01

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

  1. Expression, purification, crystallization and preliminary X-ray analysis of a novel N-substituted branched-chain l-amino-acid dioxygenase from Burkholderia ambifaria AMMD

    Diffraction data were collected to a limiting resolution of 2.4 Å from a crystal of selenomethionyl-labelled SadA, an l-amino-acid dioxygenase. Ferrous ion- and α-ketoglutarate-dependent dioxygenase from Burkholderia ambifaria AMMD (SadA) catalyzes the C3-hydroxylation of N-substituted branched-chain l-amino acids, especially N-succinyl-l-leucine, coupled to the conversion of α-ketoglutarate to succinate and CO2. SadA was expressed in Escherichia coli, purified and crystallized using the sitting-drop vapour-diffusion method at 293 K. Crystals of selenomethionine-substituted SadA were obtained using a reservoir solution containing PEG 3000 as the precipitant at pH 9.5 and diffracted X-rays to 2.4 Å resolution. The crystal belonged to space group P212121, with unit-cell parameters a = 49.3, b = 70.9, c = 148.2 Å. The calculated Matthews coefficient (VM = 2.1 Å3 Da−1, 41% solvent content) suggested that the crystal contains two molecules per asymmetric unit

  2. Synthesis, Characterization, and Biological Studies of Binuclear Copper(II Complexes of (2E-2-(2-Hydroxy-3-Methoxybenzylidene-4N-Substituted Hydrazinecarbothioamides

    P. Murali Krishna

    2013-01-01

    Full Text Available Four novel binuclear copper(II complexes [1–4] of (2E-2-(2-hydroxy-3-methoxybenzylidene-4N-substituted hydrazinecarbothioamides, (OH(OCH3C6H4CH=NNHC(SNHR, where R = H (L1, Me (L2, Et (L3, or Ph (L4, have been synthesized and characterized. The FT-IR spectral data suggested the attachment of copper(II ion to ligand moiety through the azomethine nitrogen, thioketonic sulphur, and phenolic-O. The spectroscopic characterization indicates the dissociation of dimeric complex into mononuclear [Cu(LCl] units in polar solvents like DMSO, where L is monoanionic thiosemicarbazone. The DNA binding properties of the complexes with calf thymus (CT DNA were studied by spectroscopic titration. The complexes show binding affinity to CT DNA with binding constant (Kb values in the order of 106 M−1. The ligands and their metal complexes were tested for antibacterial and antifungal activities by agar disc diffusion method. Except for complex 4, all complexes showed considerable activity almost equal to the activity of ciprofloxacin. These complexes did not show any effect on Gram-negative bacteria, whereas they showed moderate activity for Gram-positive strains.

  3. Ligand-Free, Cu- and Fe-Catalyzed Selective Ring-Opening Arylations of Benzoxazoles with Aryl Iodides.

    He, Yue; Mao, Jincheng; Rong, Guangwei; Yan, Hong; Zhang, Guoqi

    2016-06-01

    Cu- or Fe-based catalyst systems have been reported to selectively catalyze the N,N-diarylation or N-monoarylation of benzoxazoles ring-opening with aryl iodides in the absence of additional added ligand in polyethylene glycol under an inert atmosphere. Two types of coupling products (triphenylamines and diphenylamines) have been examined and the reaction routes can be simply controlled by changing the metal salts (Cu or Fe) as catalyst. A range of substrates have been investigated for the diverse reactions, and the corresponding arylation products were achieved in good to high yields. This selective, low-cost, and environmentally friendly protocol displays great potential for replacing existing methodologies as well as extending the synthetic applications of benzoxazoles. PMID:27037845

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

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

    2015-09-18

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

  5. 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

    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.

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

    Mustafa M. El-Abadelah

    2009-07-01

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

  7. Anthocyans fail to suppress transformation of aryl hydrocarbon receptor induced by dioxin.

    Mukai, Rie; Fukuda, Itsuko; Hosokawa, Keizo; Nishiumi, Shin; Kaneko, Atsushi; Ashida, Hitoshi

    2005-05-01

    Dioxins induce adverse effects through transformation of the cytosolic aryl hydrocarbon receptor (AhR). Our previous study found that flavones and flavonols at dietary levels suppress AhR transformation. In the present study, we investigated whether 20 anthocyans dissolved in trifluoroacetic acid (TFA)-MeOH suppressed AhR transformation in a cell-free system and in Hepa-1c1c7 cells. Although four compounds at 50 muM suppressed 0.1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AhR transformation and their effects were dose-dependent in the cell-free system, they were ineffective at 0.5 muM, which is close to physiological concentration. Moreover, no anthocyan at 50 muM tested here suppressed 0.1 nM TCDD-induced AhR transformation in Hepa-1c1c7 cells. We also confirmed that protocatechuic acid and related compounds, which are possible metabolites of anthocyans, did not affect the transformation in the cell-free system. It is concluded that anthocyans are not suitable candidates for protection from dioxin toxicity. PMID:15914907

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

    Rita M. Borik

    2007-08-01

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

  9. Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents

    Cavit Kazaz

    2007-12-01

    Full Text Available 1-Aryl-3-phenethylamino-1-propanone hydrochlorides 1-10, which are potentialpotent cytotoxic agents, were synthesized via Mannich reactions using paraformaldehyde,phenethylamine hydrochloride as the amine component and acetophenone, 4’-methyl-, 4’-methoxy-, 4’-chloro-, 4’-fluoro-, 4’-bromo-, 2’,4’-dichloro-, 4’-nitro-, 4’-hydroxyacetophenone or 2-acetylthiophene as the ketone component. Yields were in the87-98 % range. Of the compounds synthesized, compounds 2, 6-8 and 10 were new. Theoptimum reaction conditions were investigated by changing the mol ratios of the reactants,the solvents and the acidity levels using 1 and 10 as representative targets. It was observedthat the best mol ratio of the ketone, paraformaldehyde and phenethylamine hydrochloridewas 1:1.2:1 (compared with a 2:2.1 ratio, and the most suitable reaction medium wasethanol containing concentrated hydrochloric acid (compared with only ethanol or nosolvent. This study may serve as a guide for the conditions of the reactions to synthesizecompounds having similar chemical structures.

  10. Synthesis, structures, spectroscopy and antimicrobial properties of complexes of copper(II) with salicylaldehyde N-substituted thiosemicarbazones and 2,2'-bipyridine or 1,10-phenanthroline.

    Lobana, Tarlok S; Indoria, Shikha; Jassal, Amanpreet Kaur; Kaur, Harpreet; Arora, Daljit S; Jasinski, Jerry P

    2014-04-01

    Among the biometals (Cu, Co, Ni-cofactors in many enzymes), copper derivatives of O, N, S-donor salicylaldehyde thiosemicarbazones have received considerable attention owing to their potential biological applications. Eight new complexes of salicylaldehyde-N-substituted thiosemicarbazones [5-MeO-2-HO-C₆H₄-C(2)(H)N(3)-N(2)H-C(1)(S)-N(1)HR; R = Me, H2L(1); Et, H₂L(1), Ph, H₂L(3), H, H₂L(4)] with copper(II), namely, [Cu(κ(3)-O,N,S-L)( κ(2)-N,N-L')] {(L)(2-) = (L(1))(2-), L' = bipy, 1, phen, 2; (L)(2-) = (L(2))(2-), L' = bipy, 3, phen, 4; (L)(2-) = (L(3))(2-), L' = bipy, 5, phen, 6; (L)(2-) = (L(4))(2-), L' = bipy, 7, phen, 8} have been isolated. Complexes have slightly distorted square pyramidal geometry around the metal center (τ parameter = 0.243-0.357) and display weak to intense fluorescence in the region, 375-475 nm. These copper complexes have shown significant growth inhibitory activity (antimicrobial activity) against Staphylococcus aureus (MTCC740), methicillin resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae 1 (MTCC109), Shigella flexneri (MTCC1457), Pseudomonas aeruginosa (MTCC741) and Candida albicans (MTCC227). The activity against MRSA is an interesting observation as the commercially available gentamycin is found to be inactive against this bacterial strain. Specifically complex 5 formed by 5-methoxysalicylaldehyde-N-phenylthiosemicatbazone has shown novel antimicrobial activity against various bacteria and yeast investigated. PMID:24583354

  11. Influence of the structure of bidentate organophosphorus compounds and their extraction capacity

    This paper studies the variation of the extraction capacity within a broad series of didentate organophosphorus compounds, from diphosphine dioxides to carbamoylphosphine oxides and phosphonates. The authors consider the disputed questions of the coordination of the actinides when carbamoyl compounds are used and they consider whether an effect of anomalous aryl strenghening exists in these systems. The compounds used are presented. The extraction of microquantities of americium and other actinides was performed from nitric acid media

  12. Radical C-H arylations of (hetero)arenes catalysed by gallic acid.

    Perretti, Marcelle D; Monzón, Diego M; Crisóstomo, Fernando P; Martín, Víctor S; Carrillo, Romen

    2016-07-12

    Gallic acid efficiently catalyses radical arylations in water-acetone at room temperature. This methodology proved to be versatile and scalable. Therefore, it constitutes a greener alternative to arylation. Moreover, considering that gallic acid is an abundant vegetable tannin, this work also unleashes an alternative method for the reutilisation of bio-wastes. PMID:26804947

  13. Copper-Catalyzed Diastereoselective Arylation of Tryptophan Derivatives: Total Synthesis of (+)-Naseseazines A and B

    Kieffer, Madeleine E.; Chuang, Kangway V.; Reisman, Sarah E.

    2013-01-01

    A copper-catalyzed arylation of tryptophan derivatives is reported. The reaction proceeds with high site- and diastereoselectivity to provide aryl pyrroloindoline products in one step from simple starting materials. The utility of this transformation is highlighted in the five-step syntheses of the natural products (+)-naseseazine A and B.

  14. p-Toluenesulphonic acid-promoted, I2-catalysed sulphenylation of pyrazolones with aryl sulphonyl hydrazides.

    Zhao, Xia; Zhang, Lipeng; Li, Tianjiao; Liu, Guiyan; Wang, Haomeng; Lu, Kui

    2014-11-01

    Aryl pyrazolone thioethers were synthesized via the I2-catalysed cross-coupling of pyrazolones with aryl sulphonyl hydrazides in the presence of p-toluenesulphonic acid, which has been proposed to promote the reaction by facilitating the decomposition of sulphonyl hydrazides. PMID:25225659

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

    Ahlquist, Mårten Sten Gösta; Norrby, Per-Ola

    2007-01-01

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

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

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

    2015-12-21

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

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

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

    2012-04-16

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

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

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

    2016-03-01

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

  19. Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum.

    Thillainayagam, Mahalakshmi; Anbarasu, Anand; Ramaiah, Sudha

    2016-08-21

    The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds. PMID:27185536

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

    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.

  1. Synthesis of 5-arylidine amino-1,3,4-thiadiazol-2-[(N-substituted benzyol)]sulphonamides endowed with potent antioxidants and anticancer activity induces growth inhibition in HEK293, BT474 and NCI-H226 cells

    Chhajed, Mahavir; Shrivastava, Anil Kumar; Taile, Vijay

    2013-01-01

    Abstract A series of imines 5-amino-1,3,4-thiadiazol-2-[(N-substituted benzyol)]sulphonamide derivatives were synthesized from various aromatic aldehydes and substituted with benzoyl acetazolamides under different reaction conditions and were evaluated for their antioxidant and free radical scavenging, antimitotic activity by Allium cepa meristem root model and cytotoxicity activity against HEK 293 (human epidermal kidney cell line), BT474 (breast cancer cell line) and NCI-H226 (lung cancer c...

  2. Role of the Aryl Hydrocarbon Receptor in Colon Neoplasia

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

    2015-07-31

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

  3. Synthesis of (18) F-Difluoromethylarenes from Aryl (Pseudo) Halides.

    Shi, Hang; Braun, Augustin; Wang, Lu; Liang, Steven H; Vasdev, Neil; Ritter, Tobias

    2016-08-26

    A general method for the synthesis of [(18) F]difluoromethylarenes from [(18) F]fluoride for radiopharmaceutical discovery is reported. The method is practical, operationally simple, tolerates a wide scope of functional groups, and enables the labeling of a variety of arenes and heteroarenes with radiochemical yields (RCYs, not decay-corrected) from 10 to 60 %. The (18) F-fluorination precursors are readily prepared from aryl chlorides, bromides, iodides, and triflates. Seven (18) F-difluoromethylarene drug analogues and radiopharmaceuticals including Claritin, fluoxetine (Prozac), and [(18) F]DAA1106 were synthesized to show the potential of the method for applications in PET radiopharmaceutical design. PMID:27491349

  4. Highly Efficient N-Monomethylation of Primary Aryl Amines

    PENG, Yiyuan; LIU, Hanliang; TANG, Min; CAI, Lisheng; PIKE, Victor

    2009-01-01

    A highly efficient method for specific synthesis of N-monomethylarylamines is presented. Anilines were treated with acetic anhydride and triethylamine in dry CH2Cl2 to give the corresponding acetamides. The subsequent N-monomethylation of acetyl aryl amines with methyl iodide and Nail in THF introduced methyl group. Acid hy- drolysis of the N-methyl acetanilides in ethylene glycol generated the corresponding N-methyl-N-aryi amines in high yields. This method was also used to synthesize (E)-2-bromo-5-(4-methylaminostyryl)pyridine that may be useful as an amyloid imaging agent for Alzheimer's disease.

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

    Burke, Anthony J

    2014-01-01

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

  6. Role of the Aryl Hydrocarbon Receptor in Colon Neoplasia

    Guofeng Xie

    2015-07-01

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

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

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

    2011-03-29

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

  8. Synthetic studies towards putative yuremamine using an iterative C(sp(3))-H arylation strategy.

    Calvert, Matthew B; Sperry, Jonathan

    2016-06-28

    An overview of an iterative, 8-aminoquinoline (AQ)-directed C(sp(3))-H arylation strategy towards the pyrroloindole structure initially assigned to the alkaloid yuremamine is described. During initial efforts using a model indane system, it was discovered that the iodoresorcinol unit was not a viable C(sp(3))-H arylation partner when masked as its dimethyl ether but upon switching to a MOM group, the ether oxygen served to stabilise the high valent Pd intermediate during the reaction, thus promoting reductive elimination and leading to acceptable yields of the C(sp(3))-H arylation product. The second C(sp(3))-H arylation with an iodopyrogallol gave a 1,3-diarylated model yuremamine system possessing the desired 1,3-cis relationship. When the successful model studies were applied to a pyrroloindole system in pursuit of yuremamine, it became apparent that C9 underwent competing C(sp(2))-H arylation if left vacant, but installing a tryptamine side chain at this site prevented the desired C(sp(3))-H arylation from occurring altogether. However, a C9-methyl pyrroloindole underwent iterative C(sp(3))-H arylation at C1 with an iodoresorcinol followed by C3 with an iodopyrogallol to give a diarylated product with the aryl groups in the undesired 1,3-trans-relationship, arising from epimerisation at C1 during the second C(sp(3))-H arylation event. Although the synthesis of putative yuremamine was not accomplished, several findings are disclosed that will serve as useful additions to the burgeoning field of directed C(sp(3))-H arylations and related C-H functionalization reactions. PMID:26891188

  9. Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

    Andrea Caporale

    2014-02-01

    Full Text Available Two efficient protocols for the palladium-catalyzed synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides in the absence of copper were developed. A simple catalytic system consisting of Pd(OAc2 and P(p-tol3 using DBU as the base and THF as the solvent was found to be highly effective for the coupling reaction of 2-methyl-3-butyn-2-ol (4 with a wide range of aryl bromides in good to excellent yields. Analogously, the synthesis of aryl-2-methyl-3-butyn-2-ols was performed also through the decarboxylative coupling reaction of 4-hydroxy-4-methyl-2-pentynoic acid with aryl bromides, using a catalyst containing Pd(OAc2 in combination with SPhos or XPhos in the presence of tetra-n-butylammonium fluoride (TBAF as the base and THF as the solvent. Therefore, new efficient approaches to the synthesis of terminal acetylenes from widely available aryl bromides rather than expensive iodides and using 4 or propiolic acid rather than TMS-acetylene as inexpensive alkyne sources are described.

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

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

    2016-03-01

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

  11. RETINOID METABOLISM IN FISH EMBRYOS FROM SENSITIVE AND RESISTANT POPULATIONS EXPOSED TO DIOXIN-LIKE COMPOUNDS

    Early developmental stages of fish are extremely sensitive to a class of toxic and persistent environmental contaminants known as dioxin-like compounds (DLCs). Most of the toxicological actions of DLCs are mediated via the Aryl hydrocarbon Receptor (AhR) that regulates transcript...

  12. Ring closing and opening reactions leading to aza-polycyclic aromatic compounds

    Kethe, Anila; Li, Ang; Klumpp, Douglas A.

    2012-01-01

    A series of functionalized aza-polycyclic aromatic compounds were prepared by a superacid-promoted ring closing and opening reaction cascade. A reaction mechanism is proposed, which involves reactive dicationic intermediates. A key step in the conversions involves ipso protonation of an aryl group and elimination of an alkyl phenyl group.

  13. Pd-Catalyzed and Copper Assisted Regioselective Sequential C2 and C7 Arylation of Thiazolo[5,4-f]quinazolin-9(8H)-one with Aryl Halides.

    Harari, Marine; Couly, Florence; Fruit, Corinne; Besson, Thierry

    2016-07-01

    A selective functionalization of thiazolo[5,4-f]quinazolin-9(8H)-one has been developed through sequential activation of C-H bonds to furnish diarylated compounds. This strategy allows the regioselective C2 and C7 arylation by a judicious choice of coupling partners and bases, requiring no additional ligands or directing groups. Differently substituted N(8)-benzylated-2,7-diaryl-thiazoloquinazolin-9(8H)-ones were thereby obtained in a facile manner. A one-pot procedure was also performed. These protocols provide a synthetically useful route for late-stage functionalization of this highly valuable scaffold, required in drug discovery. PMID:27314437

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

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

    2016-01-01

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

  15. High-resolution laser spectroscopy and magnetic effect of the B~2E′←X~2A2′ transition of the 15N substituted nitrate radical

    Rotationally resolved high-resolution fluorescence excitation spectra of the 0–0 band of the B~2E′←X~2A2′ 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~2A2′ (υ″ = 0, k″ = 0, N″ = 1, J″ = 0.5 and 1.5) to the 2E3/2′ (J′ = 1.5), 2E1/2′ (J′ = 0.5), and 2E1/2′ (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~2E′ (υ = 0) state and surrounding dark vibronic states. Some series of rotational lines other than those from the X~2A2′ (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~2E1/2′ (υ = 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 2E1/2′ and 2E3/2′ spin-orbit components were identified, and the spin-orbit interaction constant of the B~2E′ (υ = 0) state was estimated to be −12 cm−1 as the lower limit

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

    Paul Knochel

    2011-09-01

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

  17. Phase Transfer Catalyzed Synthesis under Ultrasonic Irradiation and Bioactivity of N'-(4,6-Disubstituted-pyrimidin-2-yl)-N-(5-aryl-2-furoyl) Thiourea Derivatives

    KE,Shao-Yong; WEI,Tai-Bao; XUE,Si-Jia; DUAN,Li-Ping; GUO,Yan-Ling

    2004-01-01

    @@ Acylthiourea derivatives are useful as pesticides, herbicides, fungicides and regulator for plant growth, and also as important intermediates in the organic synthesis. In recent years, phase transfer catalysis reaction technique has been widely recognized as an efficient synthetic tool and attracted much attention. In view of these observations, a series of 5-aryl-2-furoyl thioureas containing substituted pyrimidine ring were synthesized using PEG-400 as solid-liquid phase transfer catalyst under ultrasonic irradiation. All of the new compounds have been exactly determined by IR, 1H NMRand elemental analysis.

  18. Identification and biological characterization of 6-aryl-7-isopropylquinazolinones as novel TRPV1 antagonists that are effective in models of chronic pain.

    Culshaw, Andrew J; Bevan, Stuart; Christiansen, Martin; Copp, Prafula; Davis, Andrew; Davis, Clare; Dyson, Alex; Dziadulewicz, Edward K; Edwards, Lee; Eggelte, Hendrikus; Fox, Alyson; Gentry, Clive; Groarke, Alex; Hallett, Allan; Hart, Terance W; Hughes, Glyn A; Knights, Sally; Kotsonis, Peter; Lee, Wai; Lyothier, Isabelle; McBryde, Andrew; McIntyre, Peter; Paloumbis, George; Panesar, Moh; Patel, Sadhana; Seiler, Max-Peter; Yaqoob, Mohammed; Zimmermann, Kaspar

    2006-01-26

    Vanilloid receptor 1 (VR1, TRPV1) is a cation-selective ion channel that is expressed on primary afferent neurons and is upregulated following inflammation and nerve damage. Blockers of this channel may have utility in the treatment of chronic nociceptive and neuropathic pain. Here, we describe the optimization from a high throughput screening hit, of a series of 6-aryl-7-isopropylquinazolinones that are TRPV1 antagonists in vitro. We also demonstrate that one compound is active in vivo against capsaicin-induced hyperalgesia and in models of neuropathic and nociceptive pain in the rat. PMID:16420034

  19. Efficient One-pot Synthesis of 12-Aryl-8, 9, 10, 12-tetrahydrobenzo[a]xanthen-11-ones Under Solvent-free Conditions

    JIA Xu-dong; HAN Song-yang; DUAN Hai-feng; LIN Ying-jie; CAO Jun-gang; LIANG Da-peng; WU Mao-cheng

    2013-01-01

    Multi-component condensation of 2-naphthol,aromatic aldehydes,and cyclic 1,3-dicarbonyl compounds catalyzed by ionic liquid [NSPTEA][HSO4] was accomplished for the synthesis of a series of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-1 l-ones under solvent-flee conditions.High yields,ease recovery,short reaction time and reusability of catalyst are significant advantages.ZrOCl2·8H2O was also found to act as an effective catalyst towards this transformation.

  20. Palladium-catalyzed C(sp(3))-H Arylation of N-Boc benzylalkylamines via a deprotonative cross-coupling process.

    Hussain, Nusrah; Kim, Byeong-Seon; Walsh, Patrick J

    2015-07-27

    Diarylmethylamines are key intermediates and products in the pharmaceutical industry. Herein we disclose a novel method toward the synthesis of these important compounds via CH functionalization. Presented is a reversible deprotonation of N-Boc benzylalkylamines at the benzylic CH with in situ arylation by a NiXantPhos-based palladium catalyst (50-93 % yield, 29 examples). The method is also successful with N-Boc-tetrahydroisoquinolines. The advantages of this method are it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling. PMID:26129922

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

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

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

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

    2015-01-01

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

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

    Jiménez-Cruz, Federico; Ríos-Olivares, Hector; García-Gutiérrez, José Luis; Mar, Lubanski Fragoza

    2015-12-01

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

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

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

    2016-03-01

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

  5. A Microplate Format Assay for Real-Time Screening for New Aldolases that Accept Aryl-Substituted Acceptor Substrates.

    Ma, Huan; Enugala, Thilak Reddy; Widersten, Mikael

    2015-12-01

    Aldolases are potentially important biocatalysts for asymmetric synthesis of polyhydroxylated compounds. Fructose 6-phosphate aldolase (FSA) is of particular interest by virtue of its unusually relaxed dependency on phosphorylated substrates. FSA has been reported to be a promising catalyst of aldol addition involving aryl-substituted acceptors such as phenylacetaldehyde that can react with donor ketones such as hydroxyacetone. Improvement of the low intrinsic activity with bulky acceptor substrates of this type is of great interest but has been hampered by the lack of powerful screening protocols applicable in directed evolution strategies. Here we present a new screen allowing for direct spectrophotometric recording of retro-aldol cleavage. The assay utilizes an aldehyde reductase produced in vitro by directed evolution; it reduces the aldehyde product formed after cleavage of the aldol by FSA. The assay is suitable both for steady-state enzyme kinetics and for real-time activity screening in a 96-well format. PMID:26449620

  6. One-Pot Synthesis and Evaluation of Antileishmanial Activities of Functionalized S-Alkyl/Aryl Benzothiazole-2-carbothioate Scaffold.

    Dar, Ajaz A; Shadab, M; Khan, Suman; Ali, Nahid; Khan, Abu T

    2016-04-15

    The synthesis of hitherto unreported S-alkyl/aryl benzothiazole-2-carbothioate is reported from thiols, oxalyl chloride, and 2-aminothiophenols using 10 mol % n-tetrabutylammonium iodide (TBAI) as catalyst in acetonitrile through multicomponent reaction (MCR) strategy. The present protocol favored formation of benzothiazoles and thioesters via simultaneous formation of C-N and C-S bonds in good yields with a wide range of substrates. A few of the synthesized derivatives were evaluated for their antimicrobial activity against the protozoan parasite Leishmania donovani, a causative agent of visceral leishmaniasis (VL). Further, these compounds displayed no toxicity toward macrophage RAW 264.7 cells and are therefore nontoxic and effective antileishmanial leads. In silico docking studies were performed to understand the possible binding site interaction with trypanothione reductase (TryR). PMID:26999637

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

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

    2009-11-01

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

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

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

    2016-07-01

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

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

    M. Rocas

    2011-11-01

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

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

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

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

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

    2009-08-13

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

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

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

    2012-12-01

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

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

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

    2015-04-01

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

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

    Rocas, M; Jakubauskiene, E; Kanopka, A

    2011-11-01

    Polychlorinated dibenzo-p-dioxins (PCDDs) and related halogenated aromatic hydrocarbons (e.g., PCDFs), often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are among the most toxic synthetic compounds known. The biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR). Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene-coding transactivation domain region (exon 10, intron 10, exon 11 region), previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age). We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA. PMID:22052373

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

    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.

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

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

    2016-06-01

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

  17. Mild Palladium-Catalyzed Cyanation of (Hetero)aryl Halides and Triflates in Aqueous Media

    Cohen, Daniel T.; Buchwald, Stephen L.

    2015-01-01

    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 reve...

  18. Aryl-aldehyde formation in fungal polyketides: Discovery and characterization of a distinct biosynthetic mechanism

    Wang, Meng; Beissner, Mirko; Zhao, Huimin

    2014-01-01

    Aryl-aldehydes are a common feature in fungal polyketides, which are considered to be exclusively generated by the R domain of non-reducing polyketide synthases (NR-PKSs). However, by cloning and heterologous expression of two cryptic NR-PKS and non-ribosomal peptide synthase (NRPS)-like genes from Aspergillus terreus in Saccharomyces cerevisiae, we discovered a distinct mechanism for aryl-aldehyde formation in which a NRPS-like protein activates and reduces an aryl-acid produced by the accom...

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

    Ambrogio, I.; Fabrizi, G.; Cacchi, S.;

    2008-01-01

    tolerates a variety of functional groups, including ether, amide, alcohol, aldehyde, ketone, ester, cyano, carboxylic acid, and nitro groups. Ortho-substituted arylating agents afforded moderate yields in some cases, though good to high yields were obtained with o-iodotoluene, iodovanillin, and 1......The Heck reaction of aryl iodides and bromides with allyl ethers has been investigated. Using phosphinefree Pd(OAc)(2) in DNIF at 90 degrees C in the presence of Bu4NOAc, the reaction gave cinnamyl derivatives, usually in good to high yields, with a wide range of aryl halides. The reaction...

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

    Huang, Ronglu

    2015-03-17

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

  1. Mechanistic Considerations in the Synthesis of 2-Aryl-Indole Analogues under Bischler-Mohlau Conditions

    MacDonough, Matthew T.; Shi, Zhe; Pinney, Kevin G.

    2015-01-01

    Mechanistic insight into the pathway of the Bischler-Mohlau indole formation reaction is provided by isotopic labeling utilizing judicious incorporation of a 13C atom within the α-bromoacetophenone analogue reactant. The resulting rearranged 2-aryl indole, isolated as the major product, located the 13C isotope label at the methine carbon of the fused five-membered heterocyclic ring, which suggested that the mechanistic pathway of cyclization, in this specific example, required two equivalents of the aniline analogue reactant partner and proceeded through an imine intermediate rather than by direct formation of the corresponding 3-aryl indole accompanied by a concomitant 1,2-aryl shift rearrangement. PMID:26973358

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

    Zhao, Yang; Weix, Daniel J

    2015-03-11

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

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

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

    2016-06-01

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

  4. Oxazolidinones as novel human CCR8 antagonists.

    Jin, Jian; Wang, Yonghui; Wang, Feng; Kerns, Jeffery K; Vinader, Victoria M; Hancock, Ashley P; Lindon, Matthew J; Stevenson, Graeme I; Morrow, Dwight M; Rao, Parvathi; Nguyen, Cuc; Barrett, Victoria J; Browning, Chris; Hartmann, Guido; Andrew, David P; Sarau, Henry M; Foley, James J; Jurewicz, Anthony J; Fornwald, James A; Harker, Andy J; Moore, Michael L; Rivero, Ralph A; Belmonte, Kristen E; Connor, Helen E

    2007-03-15

    High-throughput screening of the corporate compound collection led to the discovery of a novel series of N-substituted-5-aryl-oxazolidinones as potent human CCR8 antagonists. The synthesis, structure-activity relationships, and optimization of the series that led to the identification of SB-649701 (1a), are described. PMID:17267215

  5. [11C]Carbon Monoxide in Palladium- / Selenium-Promoted Carbonylation Reactions : Synthesis of 11C-Imides, Hydrazides, Amides, Carboxylic Acids, Carboxylic Esters, Carbothioates, Ketones and Carbamoyl Compounds

    Karimi, Farhad

    2002-01-01

    [11C]Carbon monoxide in low concentrations has been used in palladium- or seleniummediated carbonylation reactions such as the synthesis of 11C-imides, hydrazides, amides, carboxylic acids, esters, carbothioates, ketones and carbamoyl compounds. In these reactions aryl iodides have been used in most cases. However, less reactive aryl triflate, chloride and bromides were activated using tetrabutylammonium iodide. The reactivities of nucleophiles may have influence on the radiochemical yield of...

  6. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  7. Chain-extended poly(aryl ether ketones)

    Robeson, L.M.; Winslow, P.A.; Matzner, M.; Harris, J.E.; Maresca, L.M.

    1992-06-09

    This patent describes a process for preparing a poly(aryl ether ketone) polymer. It comprises reacting (n) moles of HAr H with (n + 1) moles of YCOAr{sub 1}COY under Friedel-Crafts polymerization conditions; reacting the product obtained with 2XAR{sub 2}H under Friedel-Crafts polymerization conditions; reacting the product obtained with HOAr{sub 3}OH in the presence of a base and an aprotic solvent; wherein Ar and Ar{sub 1} are divalent aromatic groups, Ar{sub 2} is a divalent aromatic group wherein the substituents X and CO are in para or ortho position relative to each other, Ar{sub 3} is a residue of a dihydric phenol, X and Y are halogen, n is an integer of 1 to 50 and X is one or greater.

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

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

    2015-01-01

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

  9. Aryl hydrocarbon receptor ligands in cancer: friend and foe.

    Murray, Iain A; Patterson, Andrew D; Perdew, Gary H

    2014-12-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is best known for mediating the toxicity and tumour-promoting properties of the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as ‘dioxin’. AHR influences the major stages of tumorigenesis — initiation, promotion, progression and metastasis — and physiologically relevant AHR ligands are often formed during disease states or during heightened innate and adaptive immune responses. Interestingly, ligand specificity and affinity vary between rodents and humans. Studies of aggressive tumours and tumour cell lines show increased levels of AHR and constitutive localization of this receptor in the nucleus. This suggests that the AHR is chronically activated in tumours, thus facilitating tumour progression. This Review discusses the role of AHR in tumorigenesis and the potential for therapeutic modulation of its activity in tumours. PMID:25568920

  10. Recent Developments of C-Aryl Glucoside SGLT2 Inhibitors.

    Zhang, Yang; Liu, Zhao-Peng

    2016-03-16

    Sodium-glucose cotransporter 2 (SGLT2) is almost exclusively expressed in the proximal renal tubules. It is responsible for about 90% of the glucose reabsorption from tubular fluid. Selective inhibition of SGLT2 is expected to favor in the normalization of plasma glucose levels in T2DM patients through the prevention of renal glucose reabsorption and the promotion of glucose excretion from urine. Selective SGLT2 inhibitors have the merits to minimize the gastrointestinal side effects associated with SGLT1 inhibition, and selective SGLT2 inhibition may have a low risk of hypoglycemia. Since the C-aryl glucosides are metabolically more stable than the O-glucosides, numerous efforts have been made in the development of potent and selective C-aryl glucoside SGLT2 inhibitors, and a number of them are now used as anti-diabetes drugs in clinic or at various stages of clinical developments. Based on their structural features, in this review, these SGLT2 inhibitors are classified as three types: the phenyl/arylmethylphenyl C-glucosides, with an emphasis on the modifications on the proximal and/or the distal phenyl ring, and the spacer; the heteroarylmethylphenyl Cglucosides, with a replacement of the distal phenyl ring by a heterocycle like pyridazine, pyrimidine, thiophene and benzothiophene, thiazole, 1,3,4-thiadiazole, and triazolopyridinone; and the glucose-modified Caryl glucosides, including the glucose C-1 derived O-spiroketals, C-4 gem-difluoro analogues, C-5 and C-6 modified derivatives, dioxa-bicyclo[3.2.1]octane bridged ketals, the thioglucosides, and carbasugars. The structure-activity relationships (SARs) of each type along with their inhibitory potency against human SGLT2 and selectivity over human SGLT1 are discussed. PMID:26861002

  11. Room Temperature N-Arylation of 1,2,4-Triazoles under Ligand-Free Condition

    Nikhil V. Suramwar

    2012-01-01

    Full Text Available A simple and efficient method for N-arylation of 1,2,4-triazole at room temperature was described by the use of predominant (111 facet CuO nanoparticles as a catalyst in ligand-free condition. The catalyst was recyclable, and a variety of substrates give N-arylation product in high yield with short period of reaction time. The wide scope of this catalyst led us to investigate transformations involving less-reactive nitrogen nucleophiles, such as imidazole and pyrazoles. We were pleased to find that various derivatives of azoles were effectively coupled with aryl iodide to afford the desired N-arylated product in excellent yield.

  12. Microwave activated synthesis of 2-aryl-quinazolin-4(3H)ones

    2007-01-01

    A highly efficient synthesis of 2-aryl-quinazolin-4(3H)ones was performed by one-pot oxidative heterocyclization of 2-aminobenzamide with aldehydes in the presence of potassium permanganate in dimethylacetamide under microwave irradiation.

  13. Synthesis of 1-Benzoyl-3-aryl-4-hydroxy-4-phenylimidazolidin-2-thiones

    曾润生; 邹建平; 穆学军; 沈琪

    2003-01-01

    l-Benzoyl-3-aryl-4-hydroxy-4-phenylimidazolidin-2-thiones can be synthesized readily from the cyclization of 1-benzoyl-3-arylthioureas with bromine-acetophenone in the presence of excess triethylamiqe.

  14. An air-stable copper reagent for nucleophilic trifluoromethylthiolation of aryl halides

    Weng, Zhiqiang

    2012-12-12

    A series of copper(I) trifluoromethyl thiolate complexes have been synthesized from the reaction of CuF2 with Me3SiCF 3 and S8 (see scheme; Cu red, F green, N blue, S yellow). These air-stable complexes serve as reagents for the efficient conversion of a wide range of aryl halides into the corresponding aryl trifluoromethyl thioethers in excellent yields. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Enantioselective CuH-Catalyzed Reductive Coupling of Aryl Alkenes and Activated Carboxylic Acids.

    Bandar, Jeffrey S; Ascic, Erhad; Buchwald, Stephen L

    2016-05-11

    A new method for the enantioselective reductive coupling of aryl alkenes with activated carboxylic acid derivatives via copper hydride catalysis is described. Dual catalytic cycles are proposed, with a relatively fast enantioselective hydroacylation cycle followed by a slower diastereoselective ketone reduction cycle. Symmetrical aryl carboxyclic anhydrides provide access to enantioenriched α-substituted ketones or alcohols with excellent stereoselectivity and functional group tolerance. PMID:27121395

  16. Modular Isoquinoline Synthesis Using Catalytic Enolate Arylation and in Situ Functionalization

    Pilgrim, Ben S.; Gatland, Alice E; McTernan, Charlie T.; Procopiou, Panayiotis A; Donohoe, Timothy J

    2013-01-01

    A methyl ketone, an aryl bromide, an electrophile, and ammonium chloride were combined in a four-component, three-step, and one-pot coupling procedure to furnish substituted isoquinolines in overall yields of up to 80%. This protocol utilizes the palladium catalyzed α-arylation reaction of an enolate, followed by in situ trapping with an electrophile, and aromatization with ammonium chloride. tert-Butyl cyanoacetate participated in a similar protocol; after functionalization and decarboxylati...

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

    Zhao, Yang; Weix, Daniel J.

    2015-01-01

    The first enantioselective cross-electrophile coupling of aryl bromides with meso-epoxides to form trans-β-arylcycloalkanols is presented. The reaction is catalyzed by a combination of (bpy)NiCl2 and a chiral titanocene under reducing conditions. Yields range from 57 to 99% with 78–95% enantiomeric excess. The 30 examples include a variety of functional groups (ether, ester, ketone, nitrile, ketal, trifluoromethyl, sulfonamide, sulfonate ester), both aryl and vinyl halides, and five- to seven...

  18. Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties.

    Noreen, Mnaza; Rasool, Nasir; Gull, Yasmeen; Zubair, Muhammad; Mahmood, Tariq; Ayub, Khurshid; Nasim, Faiz-Ul-Hassan; Yaqoob, Asma; Zia-Ul-Haq, Muhammad; de Feo, Vincenzo

    2015-01-01

    A variety of novel 5-aryl thiophenes 4a-g containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT) studies were performed using the B3LYP/6-31G (d, p) basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs) analysis of all compounds 4a-g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP) mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response) were simulated at the B3LYP/6-31G (d, p) level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenyl)thiophen-2-yl)sulfonyl) acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 ± 0.11 at 15 µg/mL with IC50 17.1 µg/mL. Moreover, some other compounds 4a-f also exhibited very good inhibition against urease enzyme. PMID:26556326

  19. Synthesis, Density Functional Theory (DFT, Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties

    Mnaza Noreen

    2015-11-01

    Full Text Available A variety of novel 5-aryl thiophenes 4a–g containing sulphonylacetamide (sulfacetamide groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT studies were performed using the B3LYP/6-31G (d, p basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs analysis of all compounds 4a–g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response were simulated at the B3LYP/6-31G (d, p level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenylthiophen-2-ylsulfonyl acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 ± 0.11 at 15 µg/mL with IC50 17.1 µg/mL. Moreover, some other compounds 4a–f also exhibited very good inhibition against urease enzyme.

  20. Design, Synthesis and Pregnancy-Terminating Activity of 2-Aryl Imidazo[2,1-a]isoquinolines

    SHANG, Zhi-Cai(商志才); HU, Gui-Xiang(胡桂香); WU, Tian-Xing(吴天星); FANG, Yui-Ying(方瑞英); YU, Qing-Sen(俞庆森)

    2004-01-01

    In order to clarify the structural requirement of pregnancy-terminating drugs, the quantitative structure-activity relationship (QSAR) of 2-aryl imidazo[2,1-a]isoquinolines was studied on the basis of quantum mechanical calculation and multiple regression analysis. A Good correlation equation was obtained (r2=0.925, q2=0.871). Some new compounds were designed according to the equation. Two of them, compounds 21 and 22, were synthesized and evaluated in NIH mice. The results showed that the difference of activity between 21 (median effective dose ED50=0.943 mg/kg/day) and 22 (ED50=1.099 mg/kg/day) was small and both of them were potent. It is also agreed with the computational results. Compared with L14105 which is the most potent pregnancy-terminating agent, these two compounds possess high activity. The evaluation of the anti-implanting activity showed that they were 100% effective at tested dosage 50.0, 25.0, 12.5 mg/kg/day×3 days in oral administration, which proved the both of them had anti-implanting activity and low first-pass effects.

  1. Selective C-Arylation of 2,5-Dibromo-3-hexylthiophene via Suzuki Cross Coupling Reaction and Their Pharmacological Aspects

    Hafiz Mansoor Ikram

    2015-03-01

    Full Text Available The present study reports the synthesis of various new derivatives based on 5-aryl-2-bromo-3-hexylthiophene with moderate-to-good yields via a palladium-catalyzed Suzuki cross-coupling reaction. This coupling method involved the reaction of 2,5-dibromo-3-hexylthiophene with several arylboronic acids in order to synthesize corresponding thiophene derivatives under controlled and optimal reaction conditions. The different substituents (CH3, OCH3, Cl, F etc. present on arylboronic acids are found to have significant electronic effects on the overall properties of new products. The synthesized thiophene molecules were studied for their haemolytic, biofilm inhibition and anti-thrombolytic activities, and almost all products showed potentially good properties. The compound 2-bromo-5-(3-chloro-4-fluorophenyl-3-hexylthiophenein particular exhibited the highest values for haemolytic and bio-film inhibition activities among all newly synthesized derivatives. In addition, the compound 2-bromo-3-hexyl-5-(4-iodophenylthiophene also showed high anti-thrombolytic activity, suggesting the potential medicinal applications of these newly synthesized compounds.

  2. ULTRASOUND ASSISTED EFFICIENT AND GREENER ONE POT SYNTHESIS OF ARYL-14-H-DIBENZO [a,j]XANTHENE DERIVATIVES Ultraschall unterstützt effizientere und umweltfreundlichere ONE Eintopfsynthese ARYL-14-H-dibenzo [a, j] Xanthenderivate

    Saurabh Puri, Balbir Kaur, Anupama Parmar and Harish Kumar

    2011-07-01

    Full Text Available Aryl-14-H-dibenzo[a,j]xanthenes have been synthesized in high yields from the condensation of aryl aldehydes and 2-napthol in presence of copper perchlorate hexahydrate as catalyst at room temperature gives aryl-14-H-dibenzo[a,j]xanthenes with excellent yields under ultrasound irradiation (35 kHz. This method has the advantages of high yield, simple methodology, greener and one pot procedure.

  3. Nickel-catalyzed cross-coupling reactions of o-carboranyl with aryl iodides: facile synthesis of 1-aryl-o-carboranes and 1,2-diaryl-o-carboranes.

    Tang, Cen; Xie, Zuowei

    2015-06-22

    A nickel-catalyzed arylation at the carbon center of o-carborane cages has been developed, thus leading to the preparation of a series of 1-aryl-o-carboranes and 1,2-diaryl-o-carboranes in high yields upon isolation. This method represents the first example of transition metal catalyzed C,C'-diarylation by cross-coupling reactions of o-carboranyl with aryl iodides. PMID:25959849

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

    Lee, Insook; Jeoung, Eun Ji; Lee, Chang Kiu [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2013-03-15

    Series of (E)-1-aryl-3-(2-pyrrolyl)-2-propenones, that were aldol condensation products between pyrrole-2-carbaldehyde and m- and p-substituted acetophenones, were prepared and their {sup 1}H and {sup 13}C NMR spectra were examined to obtain the information on the conformation of the enone system. Similar studies were carried out with (E)-3-aryl-1-(2-pyrrolyl)-2-propenones that were prepared from 2-acetylpyrrole and m- and p-substituted benzaldehydes. The substituent chemical shifts were studied by applying the Hammett relationship.

  5. Short Synthesis of Sulfur Analogues of Polyaromatic Hydrocarbons through Three Palladium-Catalyzed C-H Bond Arylations.

    Hagui, Wided; Besbes, Néji; Srasra, Ezzeddine; Roisnel, Thierry; Soulé, Jean-François; Doucet, Henri

    2016-09-01

    An expeditious synthesis of a wide range of phenanthro[9,10-b]thiophene derivatives, which are a class of polyaromatic hydrocarbon (PAH) containing a sulfur atom, is reported. The synthetic scheme involves only two operations from commercially available thiophenes, 2-bromobenzenesulfonyl chlorides and aryl bromides. In the first step, palladium-catalyzed desulfitative arylation using 2-bromobenzenesulfonyl chlorides allows the synthesis of thiophene derivatives, which are substituted at the C4 position by an aryl group containing an ortho-bromo substituent. Then, a palladium-catalyzed one-pot cascade intermolecular C5-arylation of thiophene using aryl bromides followed by intramolecular arylation led to the corresponding phenanthro[9,10-b]thiophenes in a single operation. In addition, PAHs containing two or three sulfur atoms, as well as both sulfur and nitrogen atoms, were also designed by this strategy. PMID:27550151

  6. Synthesis of aryl b-N-acetylglucosamine desmodified at C-6 as potential antimicrobial agents; Sintese de b-N-acetilglicosaminideos de arila modificados em C-6 como potenciais agentes antimicrobianos

    Manfrini, Rozangela Magalhaes; Souza Filho, Jose Dias de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Exatas; Figueireido, Rute Cunha; D' Angelis, Allison Fabiano; Prado, Maria Auxiliadora Fontes; Nunan, Elziria de Aguiar; Martins, Gabriela Aires; Alves, Ricardo Jose [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Dept. de Produtos Farmaceuticos]. E-mail: ricardodylan@farmacia.ufmg.br

    2008-07-01

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

  7. 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

    Sproviero, Michael; Verwey, Anne M.R.; Rankin, Katherine M.; Witham, Aaron A.; Soldatov, Dmitriy V.; Richard A. Manderville; Fekry, Mostafa I.; Sturla, Shana J.; Sharma, Purshotam; Wetmore, Stacey D.

    2014-01-01

    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 auth...

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

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

    2009-01-01

    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 palladiu...

  9. Boryl (Hetero)aryne Precursors as Versatile Arylation Reagents: Synthesis through C–H Activation and Orthogonal Reactivity

    Demory, Emilien; Devaraj, Karthik; Orthaber, Andreas; Gates, Paul J; Pilarski, Lukasz T

    2015-01-01

    (Pinacolato)boryl ortho-silyl(hetero)aryl triflates are presented as a new class of building blocks for arylation. They demonstrate unique versatility by delivering boronate or (hetero)aryne reactivity chemoselectively in a broad range of transformations. This approach enables the unprecedented postfunctionalization of fluoride-activated (hetero)aryne precursors, for example, as substrates in transition-metal catalysis, and offers valuable new possibilities for aryl boronate postfunctionalization without the use of specialized protecting groups. PMID:26270451

  10. Nickel-catalyzed vinylation of aryl chlorides and bromides with vinyl ZnBr.MgBrCl.

    Yamamoto, Tetsuya; Yamakawa, Tetsu

    2009-05-01

    The Ni-catalyzed cross-coupling of aryl halides and vinylzinc bromide for the synthesis of styrene derivatives was investigated. Of the catalysts surveyed, the combination of Ni(acac)(2) and Xantphos was found to be the most effective for this cross-coupling. This catalyst could be used in reactions with various aryl bromides and chlorides, including electron-rich aryl chlorides such as chloroanisoles. PMID:19354270

  11. Design and synthesis of a C7-aryl piperlongumine derivative with potent antimicrotubule and mutant p53-reactivating properties.

    Punganuru, Surendra R; Madala, Hanumantha Rao; Venugopal, Sanjay N; Samala, Ramakrishna; Mikelis, Constantinos; Srivenugopal, Kalkunte S

    2016-01-01

    Small molecules that can restore biological function to the p53 mutants found in human cancers have been highly sought to increase the anticancer efficacy. In efforts to generate hybrid anticancer drugs that can impact two or more targets simultaneously, we designed and developed piperlongumine (PL) derivatives with an aryl group inserted at the C-7 position. This insertion bestowed a combretastatin A4 (CA4, an established microtubule disruptor) like structure while retaining the piperlongumine configuration. The new compounds exhibited potent antiproliferative activities against eight cancer cell lines, in particular, were more cytotoxic against the SKBR-3 breast cancer cells which harbor a R175H mutation in p53 suppressor. KSS-9, a representative aryl PL chosen for further studies induced abundant ROS generation and protein glutathionylation. KSS-9 strongly disrupted the tubulin polymerization in vitro, destabilized the microtubules in cells and induced a potent G2/M cell cycle block. More interestingly, KSS-9 showed the ability to reactivate the p53 mutation and restore biological activity to the R175H mutant protein present in SKBR3 cells. Several procedures, including immunocytochemistry using conformation-specific antibodies for p53, immunoprecipitation combined with western blotting, electrophoretic shift mobility shift assays showed a reciprocal loss of mutant protein and generation of wild-type like protein. p53 reactivation was accompanied by the induction of the target genes, MDM2, p21cip1 and PUMA. Mechanistically, the redox-perturbation in cancer cells by the hybrid drug appears to underlie the p53 reactivation process. This anticancer drug approach merits further development. PMID:26599530

  12. Novel Combretastatin-2-aminoimidazole Analogues as Potent Tubulin Assembly Inhibitors: Exploration of Unique Pharmacophoric Impact of Bridging Skeleton and Aryl Moiety.

    Chaudhary, Vikas; Venghateri, Jubina B; Dhaked, Hemendra P S; Bhoyar, Anil S; Guchhait, Sankar K; Panda, Dulal

    2016-04-14

    Combretastatin A-4 (CA-4) in phosphate and serine pro-drug forms is under phase II clinical trials. With our interest of discovering CA-4 inspired new chemical entities, a novel series of 4,5-diaryl-2-aminoimidazole analogues of the compound was designed and synthesized by an efficient and diversity feasible route involving atom economical arene C-H bond arylation. Interestingly, four compounds showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, compound 12 inhibited the proliferation of several types of cancer cells much more efficiently than CA-4. It depolymerized microtubules, induced spindle defects, and stalled mitosis in cells. Compound 12 bound to tubulin and inhibited the polymerization of tubulin in vitro. In addition, podophyllotoxin and CA-4 inhibited the binding of compound 12 to tubulin. The distinctive pharmacophoric features of the bridging motif as well as quinoline nucleus were explored. We noted also a valuable quality of compound 12 as a potential probe in characterizing new CA-4 analogues. PMID:26938120

  13. Amidines for Versatile Cobalt(III)-Catalyzed Synthesis of Isoquinolines through C-H Functionalization with Diazo Compounds.

    Li, Jie; Tang, Mengyao; Zang, Lei; Zhang, Xiaolei; Zhang, Zhao; Ackermann, Lutz

    2016-06-01

    A cobalt(III)-catalyzed C-H/N-H bond functionalization for the synthesis of 1-aminoisoquinolines from aryl amidines and diazo compounds has been developed. The reaction proceeds under mild reaction conditions, obviates the need for oxidants, produces only N2 and H2O as the byproducts, and features a broad substrate scope. PMID:27219713

  14. Iron-Catalyzed, Highly Regioselective Synthesis of alpha-Aryl Carboxylic Acids from Styrene Derivatives and CO2

    Greenhalgh, Mark D.; Thomas, Stephen P.

    2012-01-01

    The iron-catalyzed hydrocarboxylation of aryl alkenes has been developed using a highly active bench-stable iron(II) precatalyst to give alpha-aryl carboxylic acids in excellent yields and with near-perfect regioselectivity. Using just 1 mol % FeCl2, bis(imino)pyridine 6 (1 mol %), CO2 (atmospheric pressure), and a hydride source (EtMgBr, 1.2 equiv), a range of sterically and electronically differentiated aryl alkenes were transformed to the corresponding alpha-aryl carboxylic acids (up to 96...

  15. Efficient Negishi coupling reactions of aryl chlorides catalyzed by binuclear and mononuclear nickel-N-heterocyclic carbene complexes.

    Xi, Zhenxing; Zhou, Yongbo; Chen, Wanzhi

    2008-11-01

    We describe the first nickel-N-heterocyclic carbene catalyzed Negishi cross-coupling reaction of a variety of unactivated aryl chlorides, heterocyclic chlorides, aryl dichlorides, and vinyl chloride. The mononuclear and binuclear nickel-NHC complexes supported by heteroarene-functionalized NHC ligands are found to be highly efficient for the coupling of unactivated aryl chlorides and organozinc reagents, leading to biaryls and terphenyls in good to excellent yields under mild conditions. For all aryl chlorides, the binuclear nickel catalysts show activities higher than those of mononuclear nickel complexes because of possible bimetallic cooperative effect. PMID:18841915

  16. Neptunium and plutonium solvent extraction by bi- and polydentate organic phosphorus compounds

    Extraction of neptunium(4) and plutonium(4) by six bidentate organic phosphorus compounds (diphosphines, carbamoylphosphoryl compounds) and two tridentate compounds has been investigated. It is shown that from tetraalkyl to tetraaryl dioxide of methylenediphosphine a visible aryl strengthening of the complexes is observed: Np(4) and Pu(4) distribution coefficients increase, and extraction constants decrease. A similar phenomenon is observed in the process of Np(4) extraction in the series octylphenyl-ditolyl carbamoylphosphinoxide. In case of investigated tridentate extractants, when phenyl is substituted for methyl substituent, a true anomalous aryl strengthening is observed (both distribution coefficients and extraction constants increase). In the series carbamoylmethylphosphonate-phosphinate-phosphinoxide neptunium(4) and plutonium(4) extraction increases. Quantitative characteristics of equilibria are found

  17. Extraction of neptunium and plutonium by bi- and polydentate organophosphorus compounds

    The extraction of neptunium(IV) and plutonium(IV) by six bidentate organophosphorus compounds (diphosphine dioxides, carbamoylphosphoryl compounds) and two tridentate compounds was studied. It was shown that on transition from tetraalkyl- to tetraarylmethylenediphosphine dioxide, an apparent aryl strengthening of the complexes is observed: The distribution coefficients of Np(IV) and Pu(IV) increase, and the extraction constants decrease. A similar phenomenon is observed during the extraction of Np(IV) in the series of octylphenyl-ditolyl-carbamoyl-phosphine oxide. For the tridentate extractants studied, an inherent anomalous aryl strengthening is observed when the methyl substituent is replaced by phenyl (both the distribution coefficients and the extraction constants increase). The extraction of neptunium(IV) and plutonium(IV) increases in the series of carbamoylmethyl phosphonate-phosphinate-phosphine oxide. The quantitative characteristics of the equilibria were found

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

    Mechanistic toxicology has predominantly been focused on adverse effects that are caused by reactive metabolites or by reactive oxygen species. However, many important xenobiotics exert their toxicity, not by generating reactive products, but rather by altering expression of specific genes. In particular, some environmental contaminants target nuclear receptors that function as regulators of transcription. For example, binding of xenobiotic chemicals to steroid receptors is a principle mechanism of endocrine disruption. The aryl hydrocarbon receptor (AHR) mediates toxicity of dioxin-like compounds. In mice, a polymorphism in the AHR ligand-binding domain reduces binding affinity by about 10-fold in the DBA/2 strain compared with the C57BL/6 strain; consequently, dose-response curves for numerous biochemical and toxic effects are shifted about one log to the right in DBA/2 mice. In the Han/Wistar (Kuopio) (H/W) rat strain, a polymorphism causes a deletion of 38 or 43 amino acids from the AHR transactivation domain. This deletion is associated with a greater than 1000-fold resistance to lethality from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Genes in the conventional AH gene battery (e.g. CYP1A1, CYP1A2, CYP1B1, ALDH3A1, NQO1 and UGT1A1) remain responsive to TCDD in H/W rats despite the large deletion. However, the deletion may selectively alter the receptor's ability to dysregulate specific genes that are key to dioxin toxicity. We are identifying these genes using an expression array approach in dioxin-sensitive vs. dioxin-resistant rat strains and lines. Polymorphisms exist in the human AH receptor, but thus far they have not been shown to have any substantial effect on human responses to AHR-ligands

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

    Harman is a common compound in several foods, plants and beverages. Numerous studies have demonstrated its mutagenic, co-mutagenic and carcinogenic effects; however, the exact mechanism has not been fully identified. Aryl hydrocarbon receptor (AhR) is a transcription factor regulating the expression of the carcinogen-activating enzyme; cytochrome P450 1A1 (CYP1A1). In the present study, we examined the ability of harman to induce AhR-mediated signal transduction in human and rat hepatoma cells; HepG2 and H4IIE cells. Our results showed that harman significantly induced CYP1A1 mRNA in a time- and concentration-dependent manner. Similarly, harman significantly induced CYP1A1 at protein and activity levels in a concentration-dependent manner. Moreover, the AhR antagonist, resveratrol, inhibited the increase in CYP1A1 activity by harman. The RNA polymerase inhibitor, actinomycin D, completely abolished the CYP1A1 mRNA induction by harman, indicating a transcriptional activation. The role of AhR in CYP1A1 induction by harman was confirmed by using siRNA specific for human AhR. The ability of harman to induce CYP1A1 was strongly correlated with its ability to stimulate AhR-dependent luciferase activity and electrophoretic mobility shift assay. At post-transcriptional and post-translational levels, harman did not affect the stability of CYP1A1 at the mRNA and the protein levels, excluding other mechanisms participating in the obtained effects. We concluded that harman can directly induce CYP1A1 gene expression in an AhR-dependent manner and may represent a novel mechanism by which harman promotes mutagenicity, co-mutagenicity and carcinogenicity.

  20. Molecular Cage Impregnated Palladium Nanoparticles: Efficient, Additive-Free Heterogeneous Catalysts for Cyanation of Aryl Halides.

    Mondal, Bijnaneswar; Acharyya, Koushik; Howlader, Prodip; Mukherjee, Partha Sarathi

    2016-02-10

    Two shape-persistent covalent cages (CC1(r) and CC2(r)) have been devised from triphenyl amine-based trialdehydes and cyclohexane diamine building blocks utilizing the dynamic imine chemistry followed by imine bond reduction. The cage compounds have been characterized by several spectroscopic techniques which suggest that CC1(r) and CC2(r) are [2+3] and [8+12] self-assembled architectures, respectively. These state-of-the-art molecules have a porous interior and stable aromatic backbone with multiple palladium binding sites to engineer the controlled synthesis and stabilization of ultrafine palladium nanoparticles (PdNPs). As-synthesized cage-embedded PdNPs have been characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD). Inductively coupled plasma optical emission spectrometry reveals that Pd@CC1(r) and Pd@CC2(r) have 40 and 25 wt% palladium loading, respectively. On the basis of TEM analysis, it has been estimated that as small as ∼1.8 nm PdNPs could be stabilized inside the CC1(r), while larger CC2(r) could stabilize ∼3.7 nm NPs. In contrast, reduction of palladium salts in the absence of the cages form structure less agglomerates. The well-dispersed cage-embedded NPs exhibit efficient catalytic performance in the cyanation of aryl halides under heterogeneous, additive-free condition. Moreover, these materials have excellent stability and recyclability without any agglomeration of PdNPs after several cycles. PMID:26771385

  1. What Are the Potential Sites of Protein Arylation by N-Acetyl-p-benzoquinone Imine (NAPQI)?

    Leeming, Michael G; Gamon, Luke F; Wille, Uta; Donald, William A; O'Hair, Richard A J

    2015-11-16

    Acetaminophen (paracetamol, APAP) is a safe and widely used analgesic medication when taken at therapeutic doses. However, APAP can cause potentially fatal hepatotoxicity when taken in overdose or in patients with metabolic irregularities. The production of the electrophilic and putatively toxic compound N-acetyl-p-benzoquinone imine (NAPQI), which cannot be efficiently detoxicated at high doses, is implicated in APAP toxicity. Numerous studies have identified that excess NAPQI can form covalent linkages to the thiol side chains of cysteine residues in proteins; however, the reactivity of NAPQI toward other amino acid side chains is largely unexplored. Here, we report a survey of the reactivity of NAPQI toward 11 N-acetyl amino acid methyl esters and four peptides. (1)H NMR analysis reveals that NAPQI forms covalent bonds to the side-chain functional groups of cysteine, methionine, tyrosine, and tryptophan residues. Analogous reaction products were observed when NAPQI was reacted with synthetic model peptides GAIL-X-GAILR for X = Cys, Met, Tyr, and Trp. Tandem mass spectrometry peptide sequencing showed that the NAPQI modification sites are located on the "X" residue in each case. However, when APAP and the GAIL-X-GAILR peptide were incubated with rat liver microsomes that contain many metabolic enzymes, NAPQI formed by oxidative metabolism reacted with GAIL-C-GAILR exclusively. For the peptides where X = Met, Tyr, and Trp, competing reactions between NAPQI and alternative nucleophiles precluded arylation of the target peptide by NAPQI. Although Cys residues are favorably targeted under these conditions, these data suggest that NAPQI can, in principle, also damage proteins at Met, Tyr, and Trp residues. PMID:26523953

  2. Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer

    Brokken, Leon J. S.; Lundberg-Giwercman, Yvonne; Meyts, Ewa Rajpert-De; Eberhard, Jakob; Ståhl, Olof; Cohn-Cedermark, Gabriella; Daugaard, Gedske; Arver, Stefan; Giwercman, Aleksander

    2013-01-01

    In the Western world, testicular germ cell cancer (TGCC) is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing incidence of TGCC in some countries. Additionally, there is a strong genetic component that affects susceptibility. However, genetic polymorphisms that have been identified so far only partially explain the risk of TGCC. Many of the persistent environmental pollutants act through the aryl hydrocarbon receptor (AHR). AHR signaling pathway is known to interfere with reproductive hormone signaling, which is supposed to play a role in the pathogenesis and invasive progression of TGCC. The aim of the present study was to identify whether AHR-related polymorphisms were associated with risk as well as histological and clinical features of TGCC in 367 patients and 537 controls. Haplotype-tagging single-nucleotide polymorphisms (SNPs) were genotyped in genes encoding AHR and AHR repressor (AHRR). Binary logistic regression was used to calculate the risk of TGCC, non-seminoma versus seminoma, and metastasis versus localized disease. Four SNPs in AHRR demonstrated a significant allele association with risk to develop metastases (rs2466287: OR = 0.43, 95% CI 0.21–0.90; rs2672725: OR = 0.49, 95% CI: 0.25–0.94; rs6879758: OR = 0.27, 95% CI: 0.08–0.92; rs6896163: OR = 0.34, 95% CI: 0.12–0.98). This finding supports the hypothesis that compounds acting through AHR may play a role in the invasive progression of TGCC, either directly or through modification of reproductive hormone action. PMID:23420531

  3. Aryl hydrocarbon receptor downregulates MYCN expression and promotes cell differentiation of neuroblastoma.

    Pei-Yi Wu

    Full Text Available Neuroblastoma (NB is the most common malignant disease of infancy. MYCN amplification is a prognostic factor for NB and is a sign of highly malignant disease and poor patient prognosis. In this study, we aimed to investigate novel MYCN-related genes and assess how they affect NB cell behavior. The different gene expression found in 10 MYCN amplification NB tumors and 10 tumors with normal MYCN copy number were analyzed using tissue oligonucleotide microarrays. Ingenuity Pathway Analysis was subsequently performed to identify the potential genes involved in MYCN regulation pathways. Aryl hydrocarbon receptor (AHR, a receptor for dioxin-like compounds, was found to be inversely correlated with MYCN expression in NB tissues. This correlation was confirmed in a further 14 human NB samples. Moreover, AHR expression in NB tumors was found to correlate highly with histological grade of differentiation. In vitro studies revealed that AHR overexpression in NB cells induced spontaneous cell differentiation. In addition, it was found that ectopic expression of AHR suppressed MYCN promoter activity resulting in downregulation of MYCN expression. The suppression effect of AHR on the transcription of MYCN was compensated for by E2F1 overexpression, indicating that E2F1 is involved in the AHR-regulating MYCN pathway. Furthermore, AHR shRNA promotes the expression of E2F1 and MYCN in NB cells. These findings suggest that AHR is one of the upstream regulators of MYCN. Through the modulation of E2F1, AHR regulates MYCN gene expression, which may in turn affect NB differentiation.

  4. Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer

    Leon J. S. Brokken

    2013-02-01

    Full Text Available In the Western world, testicular germ cell cancer (TGCC is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing incidence of TGCC in some countries. Additionally, there is a strong genetic component that affects susceptibility. However, genetic polymorphisms that have been identified so far only partially explain the risk of TGCC. Many of the persistent environmental pollutants act through the aryl hydrocarbon receptor (AHR. AHR signalling pathway is known to interfere with reproductive hormone signalling, which is supposed to play a role in the pathogenesis and invasive progression of TGCC. The aim of the present study was to identify whether AHR-related polymorphisms were associated with risk as well as histological and clinical features of TGCC in 367 patients and 537 controls. Haplotype-tagging single nucleotide polymorphisms (SNPs were genotyped in genes encoding AHR and AHR repressor (AHRR. Binary logistic regression was used to calculate the risk of TGCC, nonseminoma versus seminoma, and metastasis versus localised disease.Four SNPs in AHRR demonstrated a significant allele association with risk to develop metastases (rs2466287: OR = 0.43, 95% CI 0.21-0.90; rs2672725: OR = 0.49, 95% CI: 0.25-0.94; rs6879758: OR = 0.27, 95% CI: 0.08-0.92; rs6896163: OR = 0.34, 95% CI: 0.12-0.98.This finding supports the hypothesis that compounds acting through AHR may play a role in the invasive progression of TGCC, either directly or through modification of reproductive hormone action.

  5. Are styrene oligomers in coastal sediments of an industrial area aryl hydrocarbon-receptor agonists?

    Hong, Seongjin; Lee, Junghyun; Lee, Changkeun; Yoon, Seo Joon; Jeon, Seungyeon; Kwon, Bong-Oh; Lee, Jong-Hyeon; Giesy, John P; Khim, Jong Seong

    2016-06-01

    Effect-directed analysis (EDA) was performed to identify the major aryl hydrocarbon receptor (AhR) agonists in sediments collected from a highly industrialized area (Lake Shihwa, Korea). Great AhR-mediated potencies were found in fractions containing aromatic compounds with log Kow values of 5-8, and relatively great concentrations of styrene oligomers (SOs) and polycyclic aromatic hydrocarbons (PAHs) were detected in those fractions. Until now, there was little information on occurrences and toxic relative potencies (RePs) of SOs in coastal environments. In the present study; i) distributions and compositions, ii) AhR binding affinities, and iii) contributions of SOs to total AhR-mediated potencies were determined in coastal sediments. Elevated concentrations of 10 SOs were detected in sediments of inland creeks ranging from 61 to 740 ng g(-1) dry mass (dm), while lesser concentrations were found in inner (mean = 33 ng g(-1) dm) and outer regions (mean = 25 ng g(-1) dm) of the lake. Concentrations of PAHs in sediments were comparable to those of SOs. 2,4-diphenyl-1-butene (SD3) was the predominant SO analogue in sediments. SOs and PAHs were accumulated in sediments near sources, and could not be transported to remote regions due to their hydrophobicity. RePs of 3 SOs could be derived, which were 1000- to 10,000-fold less than that of one representative potent AhR active PAH, benzo[a]pyrene. Although concentrations of SOs in sediments were comparable to those of PAHs, the collective contribution of SOs to total AhR-mediated potencies were rather small (plastic in the coastal environment. PMID:27043777

  6. Aryl Hydrocarbon Receptor-Dependent Pathways in Immune Regulation.

    Gargaro, M; Pirro, M; Romani, R; Zelante, T; Fallarino, F

    2016-08-01

    The idea of possible involvement of the aryl hydrocarbon receptor (AhR) in transplant tolerance can be traced back >30 years, when very low doses of dioxin-the most potent AhR ligand-were found to markedly reduce the generation of cytotoxic T lymphocytes in response to alloantigen challenge in vivo. AhR is a ligand-activated transcription factor that is activated by dioxins and other environmental pollutants. We now know that AhR can bind a broad variety of activating ligands that are disparate in nature, including endogenous molecules and those formed in the gut from food and bacterial products. Consequently, in addition to its classical role as a toxicological signal mediator, AhR is emerging as a transcription factor involved in the regulation of both innate and adaptive immune responses in various immune cell types, including lymphocytes and antigen-presenting cells (APCs). Allograft rejection is mostly a T cell-mediated alloimmune response initiated by the recognition of alloantigens presented by donor and recipient APCs to recipient CD4(+) and CD8(+) T cells. Based on those findings, AhR may function as a critical sensor of outside and inside environments, leading to changes in the immune system that may have relevance in transplantation. PMID:26751261

  7. Evodiamine as a novel antagonist of aryl hydrocarbon receptor

    Yu, Hui [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Department of Laboratory Medicine, The Affiliated Tenth People' s Hospital, Tongji University, Shanghai 200072 (China); Tu, Yongjiu; Zhang, Chun; Fan, Xia; Wang, Xi [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Wang, Zhanli [College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014 (China); Liang, Huaping, E-mail: huaping_liang@yahoo.com.cn [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China)

    2010-11-05

    Research highlights: {yields} Evodiamine interacted with the AhR. {yields} Evodiamine inhibited the specific binding of [{sup 3}H]-TCDD to the AhR. {yields} Evodiamine acts as an antagonist of the AhR. -- Abstract: Evodiamine, the major bioactive alkaloid isolated from Wu-Chu-Yu, has been shown to interact with a wide variety of proteins and modify their expression and activities. In this study, we investigated the interaction between evodiamine and the aryl hydrocarbon receptor (AhR). Molecular modeling results revealed that evodiamine directly interacted with the AhR. Cytosolic receptor binding assay also provided the evidence that evodiamine could interact with the AhR with the K{sub i} value of 28.4 {+-} 4.9 nM. In addition, we observed that evodiamine suppressed the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nuclear translocation of the AhR and the expression of CYP1A1 dose-dependently. These results suggested that evodiamine was able to bind to the AhR as ligand and exhibit antagonistic effects.

  8. A novel aryl acylamidase from Nocardia farcinica hydrolyses polyamide.

    Heumann, Sonja; Eberl, Anita; Fischer-Colbrie, Gudrun; Pobeheim, Herbert; Kaufmann, Franz; Ribitsch, Doris; Cavaco-Paulo, Artur; Guebitz, Georg M

    2009-03-01

    An alkali stable polyamidase was isolated from a new strain of Nocardia farcinica. The enzyme consists of four subunits with a total molecular weight of 190 kDa. The polyamidase cleaved amide and ester bonds of water insoluble model substrates like adipic acid bishexylamide and bis(benzoyloxyethyl)terephthalate and hydrolyzed different soluble amides to the corresponding acid. Treatment of polyamide 6 with this amidase led to an increased hydrophilicity based on rising height and tensiometry measurements and evidence of surface hydrolysis of polyamide 6 is shown. In addition to amidase activity, the enzyme showed activity on p-nitrophenylbutyrate. On hexanoamide the amidase exhibited a K(m) value of 5.5 mM compared to 0.07 mM for p-nitroacetanilide. The polyamidase belongs to the amidase signature family and is closely related to aryl acylamidases from different strains/species of Nocardia and to the 6-aminohexanoate-cyclic dimer hydrolase (EI) from Arthrobacter sp. KI72. PMID:18942140

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

    Mohagheghi MA

    2009-09-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: 4-Aryl-4H-chromenes are novel anticancer agents which induce apoptosis in cancer cells. These compounds were found to induce apoptosis by targeting the tubulin/microtubule system in cell proliferation process. The aim of this study was to report cyototoxic and apoptosis inducing activities of a new series of synthesized 4-aryl-4H-chromenes compounds."n"n Methods: The in vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated against a paned of human cancer cell lines including MCF-7 (breast carcinoma, A549 (lung carcinoma, HEPG-2 (liver carcinoma, SW-480 (colon adenocarcinoma, U87-MG (glioblastoma, 1321N1 (astrocytoma, and DAOY (medulloblastoma. The percentage of growth inhibitory activity was evaluated using MTT colorimetric assay versus controls not treated with test derivatives. The data for etoposide, a well known anticancer drug, was included for comparison. For each compound, the 50% inhibitory concentration (IC50 were determined. Apoptosis inducing activity were assessed by DAPI staining."n"n Results: Preliminary screening showed that those chromenes analogs bearing phenyl-isoxazole-3-yl substitution or the derivatives containing methoxyphenyl in chromene ring exhibited

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

    The metabolism of tritiated 2,6-dimethylnapthalene (2,6-DMN) was studied in sea urchins (Strongylocentrotus droebachiensis) feeding on marine algae (Fucus distichus). The Fucus accumulated this hydrocarbon from sea water without converting it to metabolites. Most of the tritium accumulated by the sea urchins (e.g., 70.8% after 3 days) from feeding on 2,6-DMN-exposed Fucus was present in the exoskeleton (shell and spines). Moreover, after 3 days feeding, about 90% of the tritium in the total metabolite fraction of the gonads and digestive tract of the sea urchin was present as sulfate derivatives. These metabolites were identified through hydrolysis with aryl sulfatase, followed by thin-layer chromatography of the products. After 14 days of feeding, the tritium associated with the sulfate derivatives decreased in the gonads and digestive tract to 61 and 65%, respectively, of the total metabolite fraction. Hydroxy compounds from sulfatase hydrolysis were chromatographed using multiple elutions with toluene. The hydroxy isomers were separated and the R/sub f/ values were compared to those of pure reference compounds. The data indicated that 80% of the 2,6-dimethylnaphtyl sulfate contained the sulfate on the 1 and/or 3 position of the aromatic ring. Moreover, 6-methyl-2-naphthalenemethanol was not detected, which implies that sea urchins, unlike fish, metabolize alkyl-substituted aromatic hydrocarbons primarily through aromatic ring oxidations

  11. Computational Study on the Acid Catalyzed Reactions of Fluorine-Containing 2,4-Dialkoxy-3,4-dihydro-2H-pyrans with Aromatic Compounds

    Norio Ota

    2012-02-01

    Full Text Available The reaction of 2,4-diethoxy-6-trifluoromethyl-3,4-dihydro-2H-pyran (1 with aromatic compounds in refluxing acetonitrile in the presence of p-toluenesulfonic acid gave the mixture of 4-aryl-2-trifluoromethyl-4H-pyrans (3 and 6-aryl-1,1,1-trifluorohexa-3,5-dien-2-ones (4. In contrast, the same reaction carried out in trifluoroacetic acid at ambient temperature afforded 4-aryl-2-ethoxy-6-trifluoromethyl-3,4-dihydro-2H-pyrans (2 selectively. These two types of reactions giving quite different products under each condition were studied on the basis of DFT calculations. Moreover, the proposed mechanism for the reaction of 5-trifluoroacetyl-6-trifluoromethyl-3,4-dihydro-2H-pyran (5 with aromatic compounds affording butadiene derivatives (6 exclusively was also discussed based on the calculations and comparison with the reactivity of pyrylium intermediate (7.

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

    Hernández, Karel; Parella, Teodor; Joglar, Jesús; Bujons, Jordi; Pohl, Martina; Clapés, Pere

    2015-02-16

    The introduction of aromatic residues connected by a C-C bond into the non-reducing end of carbohydrates is highly significant for the development of innovative structures with improved binding affinity and selectivity (e.g., C-aril-sLex). In this work, an expedient asymmetric "de novo" synthetic route to new aryl carbohydrate derivatives based on two sequential stereoselectively biocatalytic carboligation reactions is presented. First, the benzoin reaction of aromatic aldehydes to dimethoxyacetaldehyde is conducted, catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I. Then, the α-hydroxyketones formed are reduced by using NaBH4 yielding the anti diol. After acetal hydrolysis, the aldol addition of dihydroxyacetone, hydroxyacetone, or glycolaldehyde catalyzed by the stereocomplementary D-fructose-6-phosphate aldolase and L-rhamnulose-1-phosphate aldolase is performed. Both aldolases accept unphosphorylated donor substrates, avoiding the need of handling the phosphate group that the dihydroxyacetone phosphate-dependent aldolases require. In this way, 6-C-aryl-L-sorbose, 6-C-aryl-L-fructose, 6-C-aryl-L-tagatose, and 5-C-aryl-L-xylose derivatives are prepared by using this methodology. PMID:25640727

  13. Enhanced interfacial properties of carbon fiber composites via aryl diazonium reaction “on water”

    Highlights: • Carbon fibers are grafted with phenyl amine group via aryl diazonium reaction. • Interfacial shear strength of the carbon fibers increases by 73%. • Tensile strength of the carbon fibers does not decrease distinctly. • Using water as the reaction medium can avoid pollution from organic solvents. • Grafting via aryl diazonium reaction in one step can improve modification efficiency. - Abstract: Polyacrylonitrile-based carbon fibers were functionalized with phenyl amine group via aryl diazonium reaction “on water” to improve their interfacial bonding with resin matrix. Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy were employed to characterize ordered degree, functional groups, chemical states and morphology of carbon fiber surface, respectively. The results showed that phenyl amine groups were grafted on the fiber surface successfully. Mechanical property test results indicated that the aryl diazonium reaction in this paper could improve the interfacial shear strength by 73%, while the tensile strength was down very slightly. Hence aryl diazonium reaction “on water” could be a facile green platform to functionalize carbon fibers for many interesting applications

  14. Synthesis and evaluation of 2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)-N-(3-(trifluoromethyl)phenyl)acetamides and N-(4-chloro-3-fluorophenyl)-2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)acetamides as antimicrobial agents

    Kalpesh Parikh; Deepkumar Joshi

    2014-05-01

    A series of 2-mercapto-5-phenyl-1,3,4-oxadiazole derivatives have been condensed with different phenyl acetamide derivatives possessing fluorine atom at meta position; resulting in the formation of 2-(5-aryl- 1,3,4-oxadiazol-2-ylthio)-N-(3-(trifluoromethyl)phenyl)acetamide (5a-j) and N-(4-chloro-3-fluorophenyl)-2-(5-aryl-1,3,4-oxadiazol-2-ylthio)acetamide (5k-t) derivatives. The antimicrobial properties of the synthesized entities (5a-t) measured as their MIC (Minimum Inhibitory Concentration) values were evaluated by using the broth dilution method against Gram-positive bacteria (S. aureus and E. faecalis), Gram-negative bacteria (E. coli and P. aeruginosa) and fungi (C. albicans and A. niger). The results of antimicrobial activities (in g/ml) revealed the fact that the compounds 5a and g bearing a maximum number of fluorine atoms showed the highest potency among the synthesized compounds against the broad panel of bacterial and fungal strains. The presence of fluorine atom at the meta position in the phenyl ring of final derivatives (5a-t) brought about an enhancement of their antimicrobial properties to a notable extent.

  15. Structure-activity relationships of N-substituted 4-(trifluoromethoxy)benzamidines with affinity for GluN2B-containing NMDA receptors.

    Beinat, Corinne; Banister, Samuel D; Hoban, Jane; Tsanaktsidis, John; Metaxas, Athanasios; Windhorst, Albert D; Kassiou, Michael

    2014-02-01

    GluN2B subtype-selective NMDA antagonists represent promising therapeutic targets for the symptomatic treatment of multiple CNS pathologies. A series of N-benzyl substituted benzamidines were synthesised and the benzyl ring was further replaced with various polycyclic moieties. Compounds were evaluated for activity at GluN2B containing NMDA receptors where analogues 9, 12, 16 and 18 were the most potent of the series, replacement of the benzyl ring with polycycles resulted in a complete loss of activity. PMID:24412068

  16. 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.

    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

  17. Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

    Filipe Vilela; Skabara, Peter J; Mason, Christopher R.; Thomas D. J. Westgate; Asun Luquin; Coles, Simon J.; Hursthouse, Michael B.

    2010-01-01

    We present a series of compounds by exploiting the unusual 1,4-aryl shift observed for electron-rich 1,3-dithiole-2-thione and tetrathiafulvalene (TTF) derivatives in the presence of perchloric acid. The mechanistic features of this rearrangement are discussed since this synthetic strategy provides an alternative route for the synthesis and functionalisation of sulfur rich compounds including redox active compounds of TTFs, and a Ni dithiolene.

  18. Dramatic Substituent Effect on the CCL-catalyzed Kinetic Resolution of 1-Aryl-2,3-allenols

    XU, Dai-Wang(徐代旺); LI, Zu-Yi(李祖义); MA, Sheng-Ming(麻生明)

    2004-01-01

    Optically active 1-aryl-2,3-allenols were obtained via CCL-mediated kinetic resolution of the racemic allenols. The substitution pattern of the aromatic ring, regarding to both the type of the substituent and its position on the aromatic ring, was found to be critical for the kinetic resolution of 1-aryl-2,3-allenols.

  19. Homocoupling of aryl halides in flow: Space integration of lithiation and FeCl3 promoted homocoupling

    Aiichiro Nagaki; Yuki Uesugi; Yutaka Tomida; Jun-ichi Yoshida

    2011-01-01

    The use of FeCl3 resulted in a fast homocoupling of aryllithiums, and this enabled its integration with the halogen–lithium exchange reaction of aryl halides in a flow microreactor. This system allows the homocoupling of two aryl halides bearing electrophilic functional groups, such as CN and NO2, in under a minute.

  20. Homocoupling of aryl halides in flow: Space integration of lithiation and FeCl3 promoted homocoupling

    Nagaki, Aiichiro; Uesugi, Yuki; Tomida, Yutaka; Yoshida, Jun-ichi

    2011-01-01

    The use of FeCl3 resulted in a fast homocoupling of aryllithiums, and this enabled its integration with the halogen–lithium exchange reaction of aryl halides in a flow microreactor. This system allows the homocoupling of two aryl halides bearing electrophilic functional groups, such as CN and NO2, in under a minute.

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

    Dong-Sheng Ma

    2010-03-01

    Full Text Available (S-N-methylpyrrolidine-2-carboxylate, a derivative of natural L-proline, was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides with aryl halides under mild conditions. A variety of N-arylamides were synthesized in good to high yields.

  2. Dithiocarbamate promoted practical synthesis of N-Aryl-2-aminobenzazoles: Synthesis of novel Aurora-A kinase inhibitor

    Naresh Kumar Katari; M Venkatanarayana; Kummari Srinivas

    2015-03-01

    Various N-aryl-2-aminobenzoxazoles and N-aryl-2-aminobenzothiazoles were synthesized from o-aminophenol and o-aminothiophenol, respectively, mediated by dithiocarbamate in one step. The salient features of this method include mild reaction condition, high yield and large scale synthesis. Application of this methodology has been demonstrated by synthesizing potent Aurora kinase-A inhibitors.

  3. C-N Coupling of nitrogen nucleophiles with aryl and heteroaryl bromides using aminoarenethiolato-copper(I) (pre-)catalyst

    Sperotto, Elena; Klink, Gerard P.M. van; Vries, Johannes G. de; Koten, Gerard van

    2010-01-01

    The activity of a library of 2-aminoarenethiolato-copper(I) (CuSAr) (pre-)catalyst was explored in the arylation reaction of amines and N-containing heterocycles with aryl and heteroaryl bromides, respectively. These CuSAr pre-catalysts are thermally stable, are soluble in common organic solvents an

  4. Homocoupling of aryl halides in flow: Space integration of lithiation and FeCl3 promoted homocoupling

    Aiichiro Nagaki

    2011-08-01

    Full Text Available The use of FeCl3 resulted in a fast homocoupling of aryllithiums, and this enabled its integration with the halogen–lithium exchange reaction of aryl halides in a flow microreactor. This system allows the homocoupling of two aryl halides bearing electrophilic functional groups, such as CN and NO2, in under a minute.

  5. Nickel-catalyzed Kumada cross-coupling reactions of tertiary alkylmagnesium halides and aryl bromides/triflates.

    Joshi-Pangu, Amruta; Wang, Chao-Yuan; Biscoe, Mark R

    2011-06-01

    We report a Ni-catalyzed process for the cross-coupling of tertiary alkyl nucleophiles and aryl bromides. This process is extremely general for a wide range of electrophiles and generally occurs with a ratio of retention to isomerization >30:1. The same procedure also accommodates the use of aryl triflates, vinyl chlorides, and vinyl bromides as the electrophilic component. PMID:21553878

  6. Synthesis, crystal structure and characterization of new biologically active Cu(II) complexes with ligand derived from N-substituted sulfonamide

    ADRIANA CORINA HANGAN; ALEXANDRU TURZA; ROXANA LIANA STAN; BOGDAN SEVASTRE; EMÖKE PÁLL; SÎNZIANA CETEAN; LUMINI¸TA SIMONA OPREAN

    2016-05-01

    A new N-sulfonamide ligand (HL1= N-(5-(4-methoxyphenyl)-[1,3,4]–thiadiazole–2-yl)-toluenesulfonamide)and two Cu(II) complexes, $[Cu(L1)­_{2}(py)_{2}]$ (C1) and $[Cu(L2)_{2}(py)_{2}(H_{2}O)]$ (C2) (HL2 = N-(5-(4-methylphenyl)-[1,3,4]–thiadiazole–2-yl)-benzenesulfonamide) were synthesized. The X-ray crystal structuresof the complexes were determined. In the complex C1, the Cu(II) ion is four-coordinated, forming a $CuN_{4}$ chromophore and in the complex C2, the Cu(II) ion is five-coordinated, forming a $CuN_{4}O$ chromophore. Theligand acts as monodentate, coordinating the Cu(II) ion through a single $N_{thiadiazole}$ atom. The molecules fromthe reaction medium (pyridine and water) are also involved in the coordination of the Cu(II) ion. The complexesC1 and C2 are square-planar and a slightly distorted square pyramidal, respectively. The compounds werecharacterized by FT-IR, electronic, EPR spectroscopic and magnetic methods. The nuclease binding activitystudies of the synthesized complexes confirm their capacity to cleave the DNA molecule. The cytotoxicitystudies were carried out on melanoma cell line WM35 which confirm that both compounds inhibit the growthof these cells. They have a higher activity compared to a platinum drug, carboplatin.

  7. Regioselective Multi-component Synthesis of 7-Aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-diones Catalyzed by n-Propylsulfonated γ-Al{sub 2}O{sub 3}

    Li, Weilin; Tian, Shuanbao; Wu, Liqiang [Xinxiang Medical Univ., Xinxiang (China)

    2013-09-15

    We have developed a straightforward method for the synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b] quinazoline-5,6-dione derivatives by nano n-propylsulfonated γ-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.

  8. N-aryl pyrrolo-tetrathiafulvalene based ligands: synthesis and metal coordination.

    Balandier, Jean-Yves; Chas, Marcos; Dron, Paul I; Goeb, Sébastien; Canevet, David; Belyasmine, Ahmed; Allain, Magali; Sallé, Marc

    2010-03-01

    A straightforward general synthetic access to N-aryl-1,3-dithiolo[4,5-c]pyrrole-2-thione derivatives 6 from acetylenedicarbaldehyde monoacetal is depicted. In addition to their potentiality as precursors to dithioalkyl-pyrrole derivatives, thiones 6 are key building blocks to N-aryl monopyrrolo-tetrathiafulvalene (MPTTF) derivatives 10. X-ray structures of four of these thiones intermediates, reminiscent of the corresponding MPTTF derivatives, are provided. When the aryl group is a binding pyridyl unit, the MPTTF derivative 10a can coordinate M(II) salts (M = Pt, Pd). The first examples of metal-directed orthogonal MPTTF-based dimers 11-14, obtained through coordination of 10a to cis-blocked square planar Pt or Pd complexes are described. Studies on the parameters influencing the dimer construction are presented, as well as first recognition properties of the resulting electron-rich clip for C(60). PMID:20143799

  9. Preparation and synthetic applications of aryl tetraflates (ArOSO2CF2CF2H).

    Rostovtsev, Vsevolod V; Bryman, Lois M; Junk, Christopher P; Harmer, Mark A; Carcani, Liane G

    2008-01-18

    We have recently developed an improved synthetic route to 1,1,2,2-tetrafluoroethanesulfonic acid (HCF2CF2SO3H, TFESA) and explored the applications of this newly available superacid in catalysis. Low volatility, ease of handling, and a convenient 1H NMR handle make this acid an attractive alternative to triflic acid. TFESA can also be converted to several of its derivatives: anhydride, sulfonyl chloride, and sulfonyl fluoride, which provide a good entry point for the synthesis of aryl sulfonates. We prepared several aryl esters of 1,1,2,2-tetrafluoroethanesulfonic acid (aryl tetraflates) and showed that they can be used in a number of palladium-catalyzed coupling reactions (Suzuki, Heck, and Buchwald-Hartwig couplings). While the reactivity of tetraflates lies between that of triflates and chlorides, tetraflates appear to be more thermally stable. Additionally, the presence of a hydrogen atom in the tetraflate group facilitates monitoring of reactions and characterization of derivatives. PMID:18085791

  10. A General Palladium-Catalyzed Hiyama Cross-Coupling Reaction of Aryl and Heteroaryl Chlorides.

    Yuen, On Ying; So, Chau Ming; Man, Ho Wing; Kwong, Fuk Yee

    2016-05-01

    A general palladium-catalyzed Hiyama cross-coupling reaction of aryl and heteroaryl chlorides with aryl and heteroaryl trialkoxysilanes by a Pd(OAc)2 /L2 catalytic system is presented. A newly developed water addition protocol can dramatically improve the product yields. The conjugation of the Pd/L2 system and the water addition protocol can efficiently catalyze a broad range of electron-rich, -neutral, -deficient, and sterically hindered aryl chlorides and heteroaryl chlorides with excellent yields within three hours and the catalyst loading can be down to 0.05 mol % Pd for the first time. Hiyama coupling of heteroaryl chlorides with heteroaryl silanes is also reported for the first time. The reaction can be easily scaled up 200 times (100 mmol) without any degasification and purification of reactants; this facilitates the practical application in routine synthesis. PMID:26998586

  11. Oculomotor deficits in aryl hydrocarbon receptor null mouse.

    Aline Chevallier

    Full Text Available The Aryl hydrocarbon Receptor or AhR, a ligand-activated transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD. Recent studies in Caenorhabditis elegans and Drosophila melanogaster show that the orthologs of the AhR are expressed exclusively in certain types of neurons and are implicated in the development and the homeostasis of the central nervous system. While physiological roles of the AhR were demonstrated in the mammalian heart, liver and gametogenesis, its ontogenic expression and putative neural functions remain elusive. Here, we report that the constitutive absence of the AhR in adult mice (AhR-/- leads to abnormal eye movements in the form of a spontaneous pendular horizontal nystagmus. To determine if the nystagmus is of vestibular, visual, or cerebellar origin, gaze stabilizing reflexes, namely vestibulo-ocular and optokinetic reflexes (VOR and OKR, were investigated. The OKR is less effective in the AhR-/- mice suggesting a deficit in the visuo-motor circuitry, while the VOR is mildly affected. Furthermore, the AhR is expressed in the retinal ganglion cells during the development, however electroretinograms revealed no impairment of retinal cell function. The structure of the cerebellum of the AhR-/- mice is normal which is compatible with the preserved VOR adaptation, a plastic process dependent on cerebellar integrity. Finally, intoxication with TCDD of control adults did not lead to any abnormality of the oculomotor control. These results demonstrate that the absence of the AhR leads to acquired central nervous system deficits in the adults. Given the many common features between both AhR mouse and human infantile nystagmus syndromes, the AhR-/- mice might give insights into the developmental mechanisms which lead to congenital eye disorders.

  12. Hepatic Aryl Hydrocarbon Receptor Attenuates Fibroblast Growth Factor 21 Expression.

    Girer, Nathaniel G; Murray, Iain A; Omiecinski, Curtis J; Perdew, Gary H

    2016-07-15

    The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in many physiological processes. Several studies indicate that AHR is also involved in energy homeostasis. Fibroblast growth factor 21 (FGF21) is an important regulator of the fasting and feeding responses. When administered to various genetic and diet-induced mouse models of obesity, FGF21 can attenuate obesity-associated morbidities. Here, we explore the role of AHR in hepatic Fgf21 expression through the use of a conditional, hepatocyte-targeted AHR knock-out mouse model (Cre(Alb)Ahr(Fx/Fx)). Compared with the congenic parental strain (Ahr(Fx/Fx)), non-fasted Cre(Alb)Ahr(Fx/Fx) mice exhibit a 4-fold increase in hepatic Fgf21 expression, as well as elevated expression of the FGF21-target gene Igfbp1 Furthermore, in vivo agonist activation of AHR reduces hepatic Fgf21 expression during a fast. The Fgf21 promoter contains several putative dioxin response elements (DREs). Using EMSA, we demonstrate that the AHR-ARNT heterodimer binds to a specific DRE that overlaps binding sequences for peroxisome proliferator-activated receptor α (PPARα), carbohydrate response element-binding protein (ChREBP), and cAMP response element-binding protein, hepatocyte specific (CREBH). In addition, we reveal that agonist-activated AHR impairs PPARα-, ChREBP-, and CREBH-mediated promoter activity in Hepa-1 cells. Accordingly, agonist treatment in Hepa-1 cells ablates potent ER stress-driven Fgf21 expression, and pre-treatment with AHR antagonist blocks this effect. Finally, we show that pre-treatment of primary human hepatocytes with AHR agonist diminishes PPARα-, glucose-, and ER stress-driven induction of FGF21 expression, indicating the effect is not mouse-specific. Together, our data show that AHR contributes to hepatic energy homeostasis, partly through the regulation of FGF21 expression and signaling. PMID:27226639

  13. Enantiospecific effects of ketoconazole on aryl hydrocarbon receptor.

    Aneta Novotna

    Full Text Available Azole antifungal ketoconazole (KET was demonstrated to activate aryl hydrocarbon receptor (AhR. Since clinically used KET is a racemic mixture of two cis-enantiomers (2R,4S-(+-KET and (2S,4R-(--KET, we examined the effects of KET enantiomers on AhR signaling pathway. (+-KET dose-dependently activated AhR in human gene reporter cell line AZ-AHR, and displayed 5-20× higher agonist activity (efficacy, as compared to (--KET; both enantiomers were AhR antagonists with equal potency (IC50. Consistently, (+-KET strongly induced CYP1A1 mRNA and protein in human HepG2 cells, while (--KET exerted less than 10% of (+-KET activity. In primary human hepatocytes, both enantiomers preferentially induced CYP1A2 over CYP1A1 mRNA and protein, and the potency of (+-KET was slightly higher as compared to (--KET. Ligand binding assay with guinea pig liver cytosols revealed that both (+-KET and (--KET are weak ligands of AhR that displaced [3H]-TCDD with comparable potency. Similarly, both enantiomers weakly transformed AhR to DNA-binding form with similar potency, as showed by EMSA, in guinea pig liver cytosolic extracts and nuclear extracts from mouse Hepa-1 cells. We also examined effects of KET on glucocorticoid receptor (GR, a regulator of AhR activity. Both KET enantiomers antagonized GR with similar potency, as revealed by gene reporter assay in AZ-GR cell line and down-regulation of tyrosine aminotransferase mRNA in human hepatocytes. Finally, we demonstrate enantiospecific antifungal activities of KET enantiomers in six Candida spp. strains. In conclusion, the significance of current study is providing the first evidence of enatiospecific effects of cis-enantiomers of ketoconazole on AhR-CYP1A pathway.

  14. Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

    Akahoshi Eiichi

    2009-06-01

    Full Text Available Abstract Background Dioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (AhR. This study focused on the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD exposure on the regulation of TH, a rate-limiting enzyme of dopamine synthesis, gene expression by AhR. Methods N2a-Rβ cells were established by transfecting murine neuroblastoma Neuro2a with the rat AhR cDNA. TH expression induced by TCDD was assessed by RT-PCR and Western blotting. Participation of AhR in TCDD-induced TH gene expression was confirmed by suppressing AhR expression using the siRNA method. Catecholamines including dopamine were measured by high-performance liquid chromatography. A reporter gene assay was used to identify regulatory motifs in the promoter region of TH gene. Binding of AhR with the regulatory motif was confirmed by an electrophoretic mobility shift assay (EMSA. Results Induction of TH by TCDD through AhR activation was detected at mRNA and protein levels. Induced TH protein was functional and its expression increased dopamine synthesis. The reporter gene assay and EMSA indicated that AhR directly regulated TH gene expression. Regulatory sequence called aryl hydrocarbon receptor responsive element III (AHRE-III was identified upstream of the TH gene from -285 bp to -167 bp. Under TCDD exposure, an AhR complex was bound to AHRE-III as well as the xenobiotic response element (XRE, though AHRE-III was not identical to XRE, the conventional AhR-binding motif. Conclusion Our results suggest TCDD directly regulate the dopamine system by TH gene

  15. Synthesis and antimicrobial activity of some new 2-(3-(4-Aryl-1-phenyl-1H-pyrazol-4-yl chroman-4-ones

    O Prakash

    2011-01-01

    Full Text Available Seven new 2-(3-(4-aryl-1-phenyl-1H-pyrazol-4-yl chroman-4-ones (4a-4g have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of 1 HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole.

  16. Modular isoquinoline synthesis using catalytic enolate arylation and in situ functionalization.

    Pilgrim, Ben S; Gatland, Alice E; McTernan, Charlie T; Procopiou, Panayiotis A; Donohoe, Timothy J

    2013-12-20

    A methyl ketone, an aryl bromide, an electrophile, and ammonium chloride were combined in a four-component, three-step, and one-pot coupling procedure to furnish substituted isoquinolines in overall yields of up to 80%. This protocol utilizes the palladium catalyzed α-arylation reaction of an enolate, followed by in situ trapping with an electrophile, and aromatization with ammonium chloride. tert-Butyl cyanoacetate participated in a similar protocol; after functionalization and decarboxylation, 3-amino-4-alkyl isoquinolines were prepared in high yield. PMID:24251885

  17. Efficient Stille cross-coupling reaction using aryl chlorides or bromides in water.

    Wolf, Christian; Lerebours, Rachel

    2003-09-19

    An efficient Stille cross-coupling reaction using a variety of aryl halides in neat water has been developed. Employing palladium-phosphinous acid catalyst [(t-Bu)(2)P(OH)](2)PdCl(2) allows formation of biaryls from aryl chlorides and bromides in good to high yields. Functional groups such as ketones and nitriles are tolerated, and organic cosolvents are not required. The air stability and solubility in water of the palladium complexes used in this study facilitate operation of the coupling reaction and product isolation. The feasibility of catalyst recycling has also been demonstrated. PMID:12968920

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

    Elizabeth P. Jones

    2011-11-01

    Full Text Available A method was developed for the synthesis of α-alkyl, α-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.

  19. Replacing Conventional Carbon Nucleophiles with Electrophiles: Nickel-Catalyzed Reductive Alkylation of Aryl Bromides and Chlorides

    Everson, Daniel A.; Jones, Brittany A.; Weix, Daniel J.

    2012-01-01

    A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (−OH, −NHTs, −OAc, −OTs, −OTf, −COMe, −NHBoc, −NHCbz, −CN, −SO2Me), and the reactions are assem...

  20. In vivo activity of aryl ozonides against Schistosoma species.

    Keiser, Jennifer; Ingram, Katrin; Vargas, Mireille; Chollet, Jacques; Wang, Xiaofang; Dong, Yuxiang; Vennerstrom, Jonathan L

    2012-02-01

    We evaluated the in vivo antischistosomal activities of 11 structurally diverse synthetic peroxides. Of all compounds tested, ozonide (1,2,4-trioxolane) OZ418 had the highest activity against adult Schistosoma mansoni, with total and female worm burden reductions of 80 and 90% (P < 0.05), respectively. Furthermore, treatment of S. haematobium-infected mice with OZ418 reduced the total worm burden by 86%. In conclusion, OZ418 is a promising antischistosomal lead compound. PMID:22106214

  1. In Vivo Activity of Aryl Ozonides against Schistosoma Species

    Keiser, Jennifer; Ingram, Katrin; Vargas, Mireille; Chollet, Jacques; Wang, Xiaofang; Dong, Yuxiang; Vennerstrom, Jonathan L.

    2012-01-01

    We evaluated the in vivo antischistosomal activities of 11 structurally diverse synthetic peroxides. Of all compounds tested, ozonide (1,2,4-trioxolane) OZ418 had the highest activity against adult Schistosoma mansoni, with total and female worm burden reductions of 80 and 90% (P < 0.05), respectively. Furthermore, treatment of S. haematobium-infected mice with OZ418 reduced the total worm burden by 86%. In conclusion, OZ418 is a promising antischistosomal lead compound.

  2. Aromatic fluorine compounds. VII. Replacement of aromatic -Cl and -NO2 groups by -F

    Finger, G.C.; Kruse, C.W.

    1956-01-01

    Replacement of -Cl by -F in aryl chlorides with potassium fluoride has been extended from 2,4-dinitrochlorobenzene to less activated halides by the use of non-aqueous solvents, especially dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). Also replacement of -NO2 by -F in substituted nitrobenzenes was studied in DMF. As a direct result of this study, many aromatic fluorine compounds can now be obtained by a relatively simple synthetic route.

  3. O-methylation of natural phenolic compounds based on green chemistry using dimethyl carbonate

    Prakoso, N. I.; Pangestu, P. H.; Wahyuningsih, T. D.

    2016-02-01

    The alkyl aryl ether compounds, of which methyl eugenol and veratraldehyde are the simplest intermediates can be synthesized by reacting eugenol and vanillin with the green reagent dimethyl carbonate (DMC). The reaction was carried out under mild of temperature and pressure. Excellent yields and selective products were obtained (95-96%) after a few hours. In the end of the reaction, the catalysts (base and Phase Transfer Catalyst) can be recovered and regenerated.

  4. 1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR2 tyrosine kinase inhibitors: synthesis, docking studies, enzymatic and cellular assays

    Queiroz, Maria João R. P.; Peixoto, Daniela; Soares, Pedro; Abreu, Rui M. V.; Froufe, Hugo J. C.; Ricardo C. Calhelha; Ferreira, Isabel C. F. R.; Costa, Raquel; Soares, Raquel

    2012-01-01

    A number of thienopyrimidines derivatives have shown potent vascular endothelial growth factor receptor 2 (VEGFR2) inhibition activity. Here, we present the synthesis of new 1-aryl-3-[4-(thieno[3,2-d) pyrimidin-4-yloxy)phenyl]ureas by promoting t he regioselective attack of the hydroxy group of the 4-aminophenol in the chlorine nucleophilic displacement on two 4-chlorinated thieno[3,2-d]pyrimidines, obtaining compounds la and 1b which were reacted with arylisocyanates to give t he corre...

  5. Synthesis and electrochemical properties of 2,6-bis(6-aryl-[1,2,4]-triazolo[3,4-b] [1,3,4]-thiadiazole-3-yl)pyridines

    Chun Xia Tan; Ruo Fei Feng; Xiao Xia Peng

    2007-01-01

    By the condensation of 2,6-bis(4-amino-5-mercapto-[1,2,4]-triazoles-2)pyridine with aromatic acid in the presence of phosphorus oxychloride. Compounds of 2,6-bis(6-aryl-[1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazole-3-yl)pyridines were synthesized.Their structures were confirmed by IR, 1H NMR spectroscopies and elemental analysis. Their electrochemical behavior and cyclic voltammogram also were be studied. The results showed that they have high ionization potentials and good affinity.

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

    Over least 15 years the complex [[99mTc](H20)3(CO)3]+ has been used as an intermediary to obtain technetium radiopharmaceuticals for applications in cardiology, neurology and oncology. Two important characteristics of this molecule are: the facility for obtaining that compound from aqueous solutions and the easiness of substituting H2O molecules by atoms of other ligand molecules. In this project we prepared new complexes [[99mTc](CMNS001-3)(H2O)(CO)3]+, where (CMNS001) = N-[(4-methoxy) benzyl]-1,2-diaminoethane, (CMNS003) = N,N'-bis-[(4-methoxy)benzyl]-1,2-diaminoethane, and assessed the uptake of these complexes in murine melanoma cancer cell B16F10 and breast cells MCF-7 and MDA-MD-231, and compared with [[99m](MIBI)6]+ uptake. In vitro uptake for both new technetium complex reached values close to 5%, for all cell lines, whereas the [[99mTc](MIBI)6]+ uptake was close to 1 %. The assessment of subcellular distribution showed high accumulation of the new complex in the membrane fraction, for MDAMB-231, while for B16F10 accumulation occurred both in membrane and cytoplasm; the concentration of [[99mTc](MIBI)6]+ was mainly in the cytoplasm portion. Biodistribution study in mice allowed to observe the capture of up to 1.6% of the administered dose per gram of tumor tissue for the complex [[99mTc](CMNS001)(H2O)(CO)3]+, whereas other organs such as heart, lung and muscle, showed uptake of about 5.6%, 6.4% and 2%, respectively. The complexes in this work showed a high rate of uptake in vitro, but was not reproduced in vivo model, which can be related to low concentration of the complexes inside the cells and reduced vascularity of tumor tissue, with lower intake of complex through the blood system. (author)

  7. ANTIMICROBIAL ACTIVITY OF DIFFERENT THIOSEMICARBAZONE COMPOUNDS AGAINST MICROBIAL PATHOGENS

    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.

  8. The slow dissociation rate of K-1602 contributes to the enhanced inhibitory activity of this novel alkyl-aryl-bearing fluoroketolide.

    Krokidis, Marios; Bougas, Anthony; Stavropoulou, Maria; Kalpaxis, Dimitrios; Dinos, George P

    2016-04-01

    Ketolides belong to the latest generation of macrolides and are not only effective against macrolide susceptible bacterial strains but also against some macrolide resistant strains. Here we present data providing insights into the mechanism of action of K-1602, a novel alkyl-aryl-bearing fluoroketolide. According to our data, the K-1602 interacts with the ribosome as a one-step slow binding inhibitor, displaying an association rate constant equal to 0.28 × 10(4 )M(-1) s(-1) and a dissociation rate constant equal to 0.0025 min(-1). Both constants contribute to produce an overall inhibition constant Ki equal to 1.49 × 10(-8 )M, which correlates very well with the superior activity of this compound when compared with many other ketolides or fluoroketolides. PMID:25807301

  9. Synthesis of 4-aryl-4,5-dihydro-1-indeno[1,2-]pyrimidines by Biginelli condensation and their antibacterial activities

    Ramandeep Kaur; Monika Bansal; Balbir Kaur; Tulika Mishra; Aruna Bhatia

    2011-07-01

    A simple and efficient method has been developed for the synthesis of series of 4-aryl-1,3,4,5-tetrahydro-2-indeno[1,2-]pyrimidine-2-thiones through Biginelli’s one-pot multicomponent condensation reaction via microwave irradiations. Then, these thiones were converted to their S-alkylated/aralkylated derivatives. The prepared heterocyclic products were structurally confirmed by analytical and spectral data and evaluated for their antibacterial activities. The results showed that this skeletal framework exhibited marked potency as antibacterial agents. The compound 2-(Ethylthio)-4-(4-Hydroxy-3-methoxyphenyl)-4,5-dihydro-1-indeno[1,2-]pyrimidines 4b have shown antibacterial activity towards all the seven clinical isolates used.

  10. Design, synthesis, and characterization of (1-(4-aryl)- 1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis.

    Venugopala, Katharigatta N; Dharma Rao, G B; Bhandary, Subhrajyoti; Pillay, Melendhran; Chopra, Deepak; Aldhubiab, Bandar E; Attimarad, Mahesh; Alwassil, Osama Ibrahim; Harsha, Sree; Mlisana, Koleka

    2016-01-01

    The novel (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives were synthesized by the click reaction of the dihydropyrimidinones, bearing a terminal alkynyl group, with various substituted aryl azides at room temperature using a catalytic amount of Cu(OAc)2 and sodium ascorbate in a 1:2 ratio of acetone and water as a solvent. The newly synthesized compounds were characterized by a number of spectroscopic techniques, such as infrared, liquid chromatography-mass spectrometry, (1)H, and (13)C nuclear magnetic resonance along with single crystal X-ray diffraction. The current procedure for the synthesis of 1,2,3-triazole hybrids with dihydropyrimidinones is appropriate for the synthesis of a library of analogs 7a-l and the method accessible here is operationally simple and has excellent yields. The title compounds 7a-l were evaluated for their in vitro antitubercular activity against H37RV and multidrug-resistant strains of Mycobacterium tuberculosis by resazurin microplate assay plate method and it was found that compound 7d was promising against H37RV and multidrug-resistant strains of M. tuberculosis at 10 and 15 μg/mL, respectively. PMID:27601885

  11. Magnetic Silica Supported Copper: A Modular Approach to Aqueous Ullmann-type Amination of Aryl Halides

    One-pot synthesis of magnetic silica supported copper catalyst has been described via in situ generated magnetic silica (Fe3O4@SiO2); the catalyst can be used for the efficacious amination of aryl halides in aqueous medium under microwave irradiation.

  12. Efficient and Simple Synthesis of 6-Aryl-1,4-dimethyl-9H-carbazoles

    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.

  13. Amination of Aryl Halides and Esters Using Intensified Continuous Flow Processing

    Thomas M. Kohl; Christian H. Hornung; John Tsanaktsidis

    2015-01-01

    Significant process intensification of the amination reactions of aryl halides and esters has been demonstrated using continuous flow processing. Using this technology traditionally difficult amination reactions have been performed safely at elevated temperatures. These reactions were successfully conducted on laboratory scale coil reactor modules with 1 mm internal diameter (ID) and on a preparatory scale tubular reactor with 6 mm ID containing static mixers.

  14. Iron-Catalyzed Acylation of Polyfunctionalized Aryl- and Benzylzinc Halides with Acid Chlorides.

    Benischke, Andreas D; Leroux, Marcel; Knoll, Irina; Knochel, Paul

    2016-08-01

    FeCl2 (5 mol %) catalyzes a smooth and convenient acylation of functionalized arylzinc halides at 50 °C (2-4 h) and benzylic zinc chlorides at 25 °C (0.5-4 h) with a variety of acid chlorides leading to polyfunctionalized diaryl and aryl heteroaryl ketones. PMID:27457108

  15. Microwave-Enhanced Cross-Coupling Reactions Involving Alkynyltrifluoroborates with Aryl Bromides

    George W. Kabalka

    2013-01-01

    Full Text Available Palladium-catalyzed alkynylation has emerged as one of the most reliable methods for the synthesis of alkynes which are often used in natural product syntheses and material science. An efficient method for coupling alkynyltrifluoroborates with various aryl bromides in the presence of a palladium catalyst has been developed using microwave irradiation. The microwave reactions are rapid and efficient.

  16. An effective synthesis of β-aryl substituted isotetronic acids via Suzuki coupling

    Huan Sheng Chen; Xia Ping Ma; Zhi Ming Li; Quan Rui Wang; Feng Gang Tao

    2008-01-01

    lsotetronic acids are of great agricultural and pharmacological relevance and occur in a number of natural products.A convenient synthetic pathway to β-aryl substituted isotetronic acid derivatives was developed via Suzuki cross-coupling of the corresponding β-bromo substituted isotetronic acid derivatives with arylboronic acids under palladium acetate catalysis.Good to excellent yields have been achieved.

  17. Covalent Functionalization and Passivation of Exfoliated Black Phosphorus via Aryl Diazonium Chemistry

    Ryder, Christopher R.; Wood, Joshua D.; Wells, Spencer A.; Yang, Yang; Jariwala, Deep; Marks, Tobin J.; Schatz, George C.; Hersam, Mark C.

    2016-01-01

    Functionalization of atomically thin nanomaterials enables the tailoring of their chemical, optical, and electronic properties. Exfoliated black phosphorus, a layered two-dimensional semiconductor exhibiting favorable charge carrier mobility, tunable bandgap, and highly anisotropic properties, is chemically reactive and degrades rapidly in ambient conditions. In contrast, here we show that covalent aryl diazonium functionalization suppresses the chemical degradation of exfoliated black phosph...

  18. Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis

    Zuo, Zhiwei; Cong, Huan; Li, Wei; Choi, Junwon; Fu, Gregory C.; MacMillan, David W. C.

    2016-01-01

    An asymmetric decarboxylative Csp3–Csp2 cross-coupling has been achieved via the synergistic merger of photoredox and nickel catalysis. This mild, operationally simple protocol transforms a wide variety of naturally abundant α-amino acids and readily available aryl halides into valuable chiral benzylic amines in high enantiomeric excess, thereby producing motifs found in pharmacologically active agents. PMID:26849354

  19. Palladium-catalyzed Coupling between Aryl Halides and Trimethylsilylacetylene Assisted by Dimethylaminotrimethyltin

    Cai Liangzhen; Yang Dujuan; Sun Zhonghua; Tao Xiaochun; Cai Lisheng; Pike Victor W

    2011-01-01

    Palladium-catalyzed coupling between aryl halides, especially less reactive ones or N-heteroaryls, and trimethylsilylacetylene in the presence of dimethylaminotrimethyltin generated the coupled products in high yields. The reaction does not need CuI and base as auxiliary agents.

  20. Brominated thiophenes as precursors in the preparation of brominated and arylated anthraquinones.

    Thiemann, Thies; Tanaka, Yasuko; Iniesta, Jesus

    2009-01-01

    Brominated anthraquinones can be synthesized directly from bromothiophenes when these are reacted with 1,4-naphthoquinones in the presence of meta-chloroperoxybenzoic acid. The bromoanthraquinones are versatile building blocks in the preparation of arylated anthraquinones and of extended pi-systems with interspersed anthraquinone units. PMID:19305356

  1. Brominated Thiophenes as Precursors in the Preparation of Brominated and Arylated Anthraquinones

    Thies Thiemann

    2009-03-01

    Full Text Available Brominated anthraquinones can be synthesized directly from bromothiophenes when these are reacted with 1,4-naphthoquinones in the presence of meta-chloroperoxybenzoic acid. The bromoanthraquinones are versatile building blocks in the preparation of arylated anthraquinones and of extended π-systems with interspersed anthraquinone units.

  2. Brominated Thiophenes as Precursors in the Preparation of Brominated and Arylated Anthraquinones

    Thies Thiemann; Jesus Iniesta; Yasuko Tanaka

    2009-01-01

    Brominated anthraquinones can be synthesized directly from bromothiophenes when these are reacted with 1,4-naphthoquinones in the presence of meta-chloroperoxybenzoic acid. The bromoanthraquinones are versatile building blocks in the preparation of arylated anthraquinones and of extended π-systems with interspersed anthraquinone units.

  3. Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

    Farhan R. Bou-Hamdan

    2011-08-01

    Full Text Available Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.

  4. Palladium-catalyzed carbonylative sonogashira coupling of aryl bromides using near stoichiometric carbon monoxide

    Neumann, Karoline T.; Laursen, Simon R.; Lindhardt, Anders T.;

    2014-01-01

    A general procedure for the palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides is reported, using near stoichiometric amounts of carbon monoxide. The method allows a broad substrate scope in moderate to excellent yields. The formed alkynone motive serves as a platform for...

  5. Iron-Catalyzed Arylation of Heterocycles via Directed C–H Bond Activation

    Sirois, John J.; Davis, Riley; DeBoef, Brenton

    2014-01-01

    The iron-catalyzed arylation of aromatic heterocycles, such as pyridines, thiophenes, and furans, has been achieved. The use of an imine directing group allowed for the ortho functionalization of these heterocycles with complete conversion in 15 min at 0 °C. Yields up to 88% were observed in the synthesis of 15 heterocyclic biaryls.

  6. Magnetic silica supported palladium catalyst: synthesis of allyl aryl ethers in water

    A simple and benign procedure for the synthesis of aryl allyl ethers has been developed using phenols, allyl acetates and magnetically recyclable silica supported palladium catalyst in water; performance of reaction in air and easy separation of the catalyst using an external mag...

  7. Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

    Shinichiro Fuse

    2013-11-01

    Full Text Available Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers.

  8. Iridium(iii)-catalyzed regioselective direct arylation of sp(2) C-H bonds with diaryliodonium salts.

    Gao, Pan; Liu, Li; Shi, Zhuangzhi; Yuan, Yu

    2016-08-01

    A regioselective direct arylation of arenes and olefins at the ortho position is reported. The key to the high selectivity is the appropriate choice of diaryliodonium salts as the arylating reagent in the presence of a cationic iridium(iii) catalyst. The coordination of the metal with an oxygen atom or a nitrogen atom and subsequent C-H activation allows for direct arylation with coupling partners. This reaction proceeds under mild reaction conditions and with a high tolerance of various functional groups including many halide functional groups. PMID:27381238

  9. Pd(OAc)2/DPPF-catalysed microwave-assisted cyanide-free synthesis of aryl nitriles

    Dinesh N Sawant; Bhalchandra M Bhanage

    2014-03-01

    This study reports microwave-assisted cyanide-free synthesis of aryl nitriles from aryl halides using palladium acetate/1,1-bis(diphenylphosphino)ferrocene as a new catalyst system. Reported protocol is a rapid, cyanide-free, single step reaction, wherein formamide acts as a solvent as well as a source of cyanide. The use of microwave increases the rate of reaction substantially and it was observed that aryl nitriles can be synthesised in 50 min of microwave irradiation compared to conventional thermal heating protocol which requires 48 h.

  10. Multipurpose Compound

    1983-01-01

    Specially formulated derivatives of an unusual basic compound known as Alcide may be the answer to effective treatment and prevention of the disease bovine mastitis, a bacterial inflammation of a cow's mammary gland that results in loss of milk production and in extreme cases, death. Manufactured by Alcide Corporation the Alcide compound has killed all tested bacteria, virus and fungi, shortly after contact, with minimal toxic effects on humans or animals. Alcide Corporation credits the existence of the mastitis treatment/prevention products to assistance provided the company by NERAC, Inc.

  11. Aryl(silyl)amino group stabilized hydridosilanediols: synthesis and characterization and use for preparation of alumino(hydrido)siloxanes.

    Wang, Xiaoping; Li, Jiancheng; Chen, Shimin; Liu, Weiping; Ye, Qingsong; Zhu, Hongping

    2016-04-12

    Aryl(silyl)amino group stabilized hydridosilanediols RSiH(OH)2 (R = N(SiMe2Ph)-2,6-iPr2C6H3 (), N(SiMe3)-2,6-iPr2C6H3 (), and N(SiMe2Ph)-2,4,6-Me3C6H2 ()) were prepared from the controlled hydrolysis of the related RSiHCl2 () each in the presence of aniline as the HCl acceptor. Reactions of with AlMe3, AliBu3, AlH(iBu)2, and AlH3·NMe3, respectively, yielded alumino(hydrido)siloxanes [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAlMe(THF)]2 (), [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAliBu(THF)]2 (), [2,6-iPr2C6H3N(SiMe2Ph)Si(H)O2]3[Al(THF)]2 (), and [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAlH(THF)]2 (). The reaction of with AlMe3 gave [2,6-iPr2C6H3N(SiMe3)Si(H)OAlMe(THF)]2 (), a compound similar to . Compounds are characterized by NMR ((1)H, (13)C, and (29)Si) and IR spectroscopy and CHN elemental analysis, of which and are further studied by X-ray crystallography. Compounds and feature cyclic structures all with the skeleton core of Si2O4Al2 while compound exhibits a bicyclic structure having a core of Si3O6Al2. Melting point measurements indicated that are thermally stable bearing the geminal SiH and SiOH groups. Compounds and are thermally stable as well with the O atom-bridged SiH and AlR (R = Me, iBu, or H) groups. PMID:26975000

  12. Allium Discoloration: Color Compounds Formed during Pinking of Onion and Leek.

    Kubec, Roman; Urajová, Petra; Lacina, Ondřej; Hajšlová, Jana; Kuzma, Marek; Zápal, Jakub

    2015-11-25

    Structures and formation pathways of compounds responsible for pink discoloration of onion and leek were studied. A procedure was developed for the isolation and purification of the color compounds from various model systems and their identification by HPLC-DAD-MS/MS. In total, structures of 15 major color compounds were tentatively determined. It was found that the pigment is a complex mixture of highly conjugated species composed of two N-substituted 3,4-dimethylpyrrole-derived rings linked by either a methine or a propenylidine bridge. These two-ring units are further modified by various C1- and C3-side chains. Experiments with isotope-labeled thiosulfinates revealed that the methine bridge and C1-side chains originate from the methyl group of methiin, whereas the C3 units are derived from the propenyl group of isoalliin. PMID:26548475

  13. PCB 126 and other dioxin-like PCBs specifically suppress hepatic PEPCK expression via the aryl hydrocarbon receptor.

    Wenshuo Zhang

    Full Text Available 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 20(th century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was evaluated with respect to its direct effects on hepatic glucose metabolism using primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed forskolin-stimulated gluconeogenesis from lactate. These effects were independent of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor affect lipid metabolism or total intracellular ATP. Interestingly, provision of cells with glycerol instead of lactate as the carbon source completely restored hepatic glucose production, indicating specific impairment in the distal arm of gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK mRNA levels without affecting glucose-6-phosphatase expression. Myricetin, a putative competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB 126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK expression in parallel with their ability to activate AhR. It therefore appears that AhR activation mediates the suppression of PEPCK expression by dioxin-like PCBs, suggesting a role for these pollutants as disruptors of energy metabolism.

  14. Direct Arylation of Pyrroles via Indirect Electroreductive C-H Functionalization Using Perylene Bisimide as an Electron-Transfer Mediator.

    Sun, Guoquan; Ren, Shuya; Zhu, Xinhai; Huang, Manna; Wan, Yiqian

    2016-02-01

    The indirect electroreductive coupling of aryl halides and pyrroles was successfully conducted using a catalytic amount of perylene bisimide as a mediator in 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide ([EMIM]NTf2)/DMSO. PMID:26800089

  15. Cooperative effect of silver in copper-catalyzed trifluoromethylation of aryl iodides using Me3SiCF3

    Weng, Zhiqiang

    2011-06-13

    An effective model of cooperative effect of silver for the coppercatalyzed trifluoromethylation of activated and unactivated aryl iodides to trifluoromethylated arenes using Me3SiCF3 was achieved with a broad substrate scope. © 2011 American Chemical Society.

  16. A Simple and Highly Efficient Preparation of Structurally Diverse Aryl β-diketoacids as HIV-1 Integrase Inhibitors

    JIANG Xiao-Hua姜晓华; LONG Ya-Qiu龙亚秋

    2004-01-01

    In order to provide a facile and practical access to structurally diverse aryl β-diketoacids, An improved and highly efficient oxalylation method was developed which employed commercially available and cheap reagents.The oxalylation of aryl methyl ketones, the key step to construct the pharmacophore of aryl β-diketoacids, was considerably facilitated by a new combination of dimethyl oxalate as an oxalic source and sodium tert-butoxide as a base. A wide variety of aryl β-diketoacids bearing different functional groups can be prepared rapidly in high yields at room t. emperature with this method, which has significant advantages over the previously reported procedures in a wider application range, much less amount of reagents, pretty higher yields and quite shorter reaction time. The bis-aryldiketoacids 3k and 31, readily prepared by this method, displayed interesting and promising inhibitory activities against HIV-1 integrase and HIV-1 replication in cells.

  17. C-H arylation of azaheterocycles: a direct ligand-free and Cu-catalyzed approach using diaryliodonium salts.

    Kumar, Dalip; Pilania, Meenakshi; Arun, V; Pooniya, Savita

    2014-09-01

    An efficient and high yielding Cu-catalyzed direct C-H arylation of azaheterocycles including oxadiazoles, thiadiazoles, benzoxazoles and benzothiazoles has been achieved by employing easily accessible diaryliodonium salts. PMID:25017573

  18. X-ray crystal structure investigation of an N-substituted ciprofloxacin:1-cyclopropyl-6-fluoro-1,4-dihydro-7-[4-(1-isovaleramido- 1-trifluoromethyl-2,2,2-trifluoroethyl)-1-piperazinyl]-4-oxoquinoline- 3-carboxylic acid

    The x-ray crystal and molecular structure of an N-substituted ciprofloxacinC25H27F7N4O4(I) was determined: sp. gr. P21/c; a=9.870(1); b=28.443(3), and c=9.534(1) A; β=99.09(1) deg., Z=4; and R=0.046 [automated CAD-4 diffractometer,λCuKα; 2687 unique reflections with I≥2σ]. Molecule I contains a flattened bicyclic 1,4-dihydro-4-oxoquinoline skeleton and a COOH group coplanar to it, which forms a strong intramolecular hydrogen bond with the 4-oxo group. The piperazine ring in I has a chair conformation, and the plane through its four C atoms forms an angle of 37 deg. with the plane through the adjacent benzene ring. Two unusual intramolecular hydrogen bonds are observed in the structure: C(sp3)-H···F-C(ar) and N(sp2)-H···F-C(sp3). In the crystal, molecules I are connected by the intermolecular hydrogen bonds ···O=C-N-H···O=C-N-H···etc., into infinite chains running along the z-axis

  19. Mechanism and Selectivity in Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Halides with Alkyl Halides

    Biswas, Soumik; Weix, Daniel J.

    2013-01-01

    The direct cross-coupling of two different electrophiles, such as an aryl halide with an alkyl halide, offers many advantages over conventional cross-coupling methods that require a carbon nucleophile. Despite its promise as a versatile synthetic strategy, a limited understanding of the mechanism and origin of cross selectivity has hindered progress in reaction development and design. Herein, we shed light on the mechanism for the nickel-catalyzed cross-electrophile coupling of aryl halides w...

  20. Palladium-Catalyzed Hydroxylation of Aryl and Heteroaryl Halides Enabled by the Use of a Palladacycle Precatalyst

    Cheung, Chi Wai; Buchwald, Stephen L.

    2014-01-01

    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.

  1. A unified approach for the synthesis of symmetrical and unsymmetrical dibenzyl ethers from aryl aldehydes through reductive etherification

    J. Sembian Ruso

    2016-05-01

    Full Text Available In this paper, we describe a simple and convenient conversion of aryl aldehydes to symmetrical dibenzyl ethers through reductive etherification. Similarly, unsymmetrical dibenzyl ether was obtained from aryl aldehyde and TES-protected benzyl alcohol. Triethyl silane with catalytic amount of InCl3 was found to be an efficient condition for the reductive etherification. Moreover, it exhibits remarkable functional group compatibility with yield ranging from good to excellent.

  2. Oxidative phosphonylation of aromatic compounds

    Effenberger, Franz; Kottmann, Hariolf

    1985-01-01

    Aryl phosphonates can be prepared in good yield from the respective arenes and tri- or dialkyphosphites by either chemical or anodic oxidation. The anodic oxidation proceeds either via phosphinium radical cations, which then attack the arenes electrophilically, or via arene radical cations, which add the trialkylphosphite as nucleophile. Aryl phosphonates are also obtained in good yield by chemical oxidation with peroxodisulfate/AgNO3 in acetonitrile/water or glacial acetic acid. The diethylp...

  3. Activation of Aryl Halides by Nickel(I) Pincer Complexes: Reaction Pathways of Stoichiometric and Catalytic Dehalogenations.

    Rettenmeier, Christoph A; Wenz, Jan; Wadepohl, Hubert; Gade, Lutz H

    2016-08-15

    Homolytic C-X bond cleavage of organohalides by the T-shaped nickel(I) complexes [LigNi(I)] 1 bearing the iso-PyrrMeBox ligand had been found previously to be the crucial activation step in the asymmetric hydrodehalogenation of geminal dihalides. Here, this mechanistic investigation is extended to aryl halides, which allowed a systematic study of the activation process by a combination of experimental data and density functional theory modeling. While the activation of both aryl chlorides and geminal dichlorides appears to proceed via an analogous transition state, the generation of a highly stabile nickel(II)aryl species in the reaction of the aryl chlorides for the former represents a major difference in the reactive behavior. This difference was found to have a crucial impact on the activity of these nickel pincer systems as catalysts in the dehalogenation of aryl chlorides compared to geminal dichlorides and highlights the importance of the regulatory pathways controlling the nickel(I) concentration throughout the catalysis. These results along with the identification and characterization of novel nickel(II)aryl species are presented. PMID:27483018

  4. N-Alkyl/aryl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbothioamide as dual-action vaginal microbicides with reverse transcriptase inhibition.

    Bala, Veenu; Mandalapu, Dhanaraju; Gupta, Sonal; Jangir, Santosh; Kushwaha, Bhavana; Chhonker, Yashpal S; Chandasana, Hardik; Krishna, Shagun; Rawat, Kavita; Krishna, Atul; Singh, Mala; Sankhwar, Satya N; Shukla, Praveen K; Maikhuri, Jagdamba P; Bhatta, Rabi S; Siddiqi, Mohammad I; Tripathi, Rajkamal; Gupta, Gopal; Sharma, Vishnu L

    2015-08-28

    The growing population and health-care burden (due to STIs and HIV) imposes a particular economic crisis over resource-poor countries. Thus a novel approach as vaginal microbicides emerges as integrated tool to control both population and anti-STIs/HIV. Our continued efforts in this field led to the synthesis of fifteen N-alkyl/aryl-4-(3-substituted-3-phenylpropyl) piperazine-1-carbothioamide (12-26) derivatives as topical vaginal microbicides which were evaluated for anti-Trichomonas, spermicidal, antifungal and reverse transcriptase (RT) inhibitory activities. All compounds were also tested for preliminary safety through cytotoxicity assays against human cervical cell line (HeLa) and the vaginal flora, Lactobacillus. Docking studies were performed to gain an insight into the binding mode and interactions of the most promising compound 12 [oxo derivative], comprising of reverse transcriptase (RT) inhibitory (72.30%), spermicidal (MEC 0.01%), anti-Trichomonas (MIC 46.72 μM) and antifungal (MIC 9.34-74.8 μM) activities, along with its hydroxyl (17) and O-alkylated 4-trifluoromethylphenoxy (22) derivative, with similar activities. The stability of compound 12 in simulated vaginal fluid (SVF) and its preliminary in vivo pharmacokinetics performed in female NZ-rabbits signifies its clinical safety in comparison to marketed spermicide Nonoxynol-9. PMID:26209833

  5. Compound odontoma

    Monica Yadav

    2012-01-01

    Full Text Available Odontomas have been extensively reported in the dental literature, and the term refers to tumors of odontogenic origin. Though the exact etiology is still unknown, the postulated causes include: local trauma, infection, inheritance and genetic mutation. The majority of the lesions are asymptomatic; however, may be accompanied with pain and swelling as secondary complaints in some cases. Here, we report a case of a compound odontome in a 14 year old patient.

  6. Magnesium compounds

    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.

  7. Microwave assisted synthesis and antimicrobial activity of novel 1-[1/2-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy-naphthalen-2/1-yl]-3-(1-phenyl-3-aryl-1H-pyrazol-4-yl-propenones

    Dongamanti Ashok

    2015-06-01

    Full Text Available A series of novel 1-[1/2-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy-naphthalen-2/1-yl]-3-(1-phenyl-3-aryl-1H-pyrazol-4-yl-propenones were design and synthesized by Click reaction followed by Claisen-Schmidt condensation under microwave irradiation and conventional heating methods. The structures of newly synthesized compounds have been established on the basis of elemental analysis, IR, 1H & 13C NMR and mass spectral data. All the compounds were screened for their antimicrobial activity.

  8. Synthesis of enyne and aryl vinyl sulfoxides: functionalization via Pummerer rearrangement.

    Souza, Frederico B; Shamim, Anwar; Argomedo, Luiz M Z; Pimenta, Daniel C; Stefani, Hélio A

    2015-11-01

    An efficient methodology for the synthesis of aryl-substituted vinyl sulfoxides through direct substitution of aryl-substituted alkynyl grignard reagents on menthyl-p-toluenesulfinate followed by Suzuki-Miyaura cross-coupling reaction has been developed. It has also been described that the reaction of alkyl-substituted and cycloalkyl-substituted alkynyl grignard reagents with menthyl-p-toluenesulfinate led to two products, i.e., alkynyl sulfoxide derivatives, as a result of substitution, and enyne sulfoxide derivatives, which resulted from substitution followed by Michael type addition. It was possible to selectively synthesize the enyne sulfoxide derivatives by changing the concentration of the grignard reagent. These alkenyl sulfoxides were transformed into the corresponding [Formula: see text]-thio aldehydes in high yields via additive Pummerer rearrangement. PMID:26232026

  9. Covalent functionalization and passivation of exfoliated black phosphorus via aryl diazonium chemistry

    Ryder, Christopher R.; Wood, Joshua D.; Wells, Spencer A.; Yang, Yang; Jariwala, Deep; Marks, Tobin J.; Schatz, George C.; Hersam, Mark C.

    2016-06-01

    Functionalization of atomically thin nanomaterials enables the tailoring of their chemical, optical and electronic properties. Exfoliated black phosphorus (BP)—a layered two-dimensional semiconductor—exhibits favourable charge-carrier mobility, tunable bandgap and highly anisotropic properties, but it is chemically reactive and degrades rapidly in ambient conditions. Here we show that covalent aryl diazonium functionalization suppresses the chemical degradation of exfoliated BP even after three weeks of ambient exposure. This chemical modification scheme spontaneously forms phosphorus–carbon bonds, has a reaction rate sensitive to the aryl diazonium substituent and alters the electronic properties of exfoliated BP, ultimately yielding a strong, tunable p-type doping that simultaneously improves the field-effect transistor mobility and on/off current ratio. This chemical functionalization pathway controllably modifies the properties of exfoliated BP, and thus improves its prospects for nanoelectronic applications.

  10. The convenient preparation of stable aryl-coated zerovalent iron nanoparticles.

    Guselnikova, Olga A; Galanov, Andrey I; Gutakovskii, Anton K; Postnikov, Pavel S

    2015-01-01

    A novel approach for the in situ synthesis of zerovalent aryl-coated iron nanoparticles (NPs) based on diazonium salt chemistry is proposed. Surface-modified zerovalent iron NPs (ZVI NPs) were prepared by simple chemical reduction of iron(III) chloride aqueous solution followed by in situ modification using water soluble arenediazonium tosylate. The resulting NPs, with average iron core diameter of 21 nm, were coated with a 10 nm thick organic layer to provide long-term protection in air for the highly reactive zerovalent iron core up to 180 °C. The surface-modified iron NPs possess a high grafting density of the aryl group on the NPs surface of 1.23 mmol/g. FTIR spectroscopy, XRD, HRTEM, TGA/DTA, and elemental analysis were performed in order to characterize the resulting material. PMID:26171295

  11. Pyridylidene ligand facilitates gold-catalyzed oxidative C–H arylation of heterocycles

    Hata, Kazuhiro; Ito, Hideto

    2015-01-01

    Summary Triaryl-2-pyridylidene effectively facilitates the gold-catalyzed oxidative C–H arylation of heteroarenes with arylsilanes as a unique electron-donating ligand on gold. The employment of the 2-pyridylidene ligand, which is one of the strongest electron-donating N-heterocyclic carbenes, resulted in the rate acceleration of the C–H arylation reaction of heterocycles over conventional ligands such as triphenylphosphine and a classical N-heterocyclic carbene. In situ observation and isolation of the 2-pyridylidene-gold(III) species, as well as a DFT study, indicated unusual stability of gold(III) species stabilized by strong electron donation from the 2-pyridylidene ligand. Thus, the gold(I)-to-gold(III) oxidation process is thought to be facilitated by the highly electron-donating 2-pyridylidene ligand. PMID:26877796

  12. Antioxidant and DNA damage inhibition activities of 4-Aryl-N-(4-arylthiazol-2-yl)-5,6-dihydro-4H-1,3,4-oxadiazine-2-carboxamides

    K Shubakara; K B Umesha; N Srikantamurthy; J Chethan

    2014-11-01

    A series of 4-aryl--(4-pheny-thiazol-2-yl)-5,6-dihydro-4-1,3,4-oxadiazine-2-carboxamides were synthesized by condensing 4-aryl-5,6-dihydro-4-1,3,4-oxadiazine-2-carboxylic acid with 2-amino-4-aryl-thiazole derivatives. The newly synthesized molecules were characterized by spectral analysis and subjected to antioxidant and DNA damage inhibition studies.

  13. Soluble N-Substituted Organosilane Polybenzimidazoles

    Klaehn, J. R.; Luther, T. A.; Orme, C. J.; Jones, M. G.; Wertsching, A. K.; Peterson, E. S.

    2007-10-01

    Six organosilane derivatives were synthesized, and are more soluble in common organic solvents (tetrahydrofuran and chloroform) than the parent polybenzimidazole. Our polymer modification pathway provides a straightforward synthesis that can be carried out at room temperature and give reasonable yields. Solution 1H NMR spectra of both the parent and deprotonated polybenzimidazoles are reported. Based upon the NMR analysis in CDCl3, nearly all of the benzimidazole N-H positions are substituted by the organosilane moieties. Some of the modified polymers have similar thermal properties compared to the parent polymer, and the average molecular weights are higher for the substituted polybenzimidazoles than the parent PBI.

  14. CuO hollow nanosphere-catalyzed cross-coupling of aryl iodides with thiols

    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.

  15. The Aryl Hydrocarbon Receptor Affects Distinct Tissue Compartments during Ontogeny of the Immune System

    Hogaboam, Jason P.; Moore, Amanda J.; Lawrence, B. Paige

    2007-01-01

    There is growing evidence that prenatal and early postnatal environmental factors influence the development and programming of the immune system, causing long-lasting negative health consequences. The aryl hydrocarbon receptor (AhR) is an important modulator of the development and function of the immune system; however, the mechanism is poorly understood. Exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin throughout gestation and during lactation yields adult offspring with persi...

  16. Dioxouranium (VI) complexes of N4- substituted aryl thiosemicarbazones derived from 2,6- diacetylpyridine

    Some seven-coordinated dioxouranium(VI) complexes of 4N-aryl substituted thiosemicarbazones derived from 2,6-diacetylpyridine were prepared in non-aqueous solvent. All the complexes were characterised by infrared, electronic and 1H NMR spectra. In all the cases the ligands behave as di basic quinquedentate (N3S2) ligands. The complexes may have distorted pentagonal bipyramidal geometry. (author)

  17. Highly Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram.

    Huang, Linwei; Zhu, Jinbin; Jiao, Guangjun; Wang, Zheng; Yu, Xingxin; Deng, Wei-Ping; Tang, Wenjun

    2016-03-24

    Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)-WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram. PMID:26933831

  18. In vivo evaluation of A-56619 (difloxacin) and A-56620: new aryl-fluoroquinolones.

    Fernandes, P B; Chu, D T; Bower, R R; Jarvis, K. P.; Ramer, N R; Shipkowitz, N

    1986-01-01

    A-56619 and A-56620 are two new aryl-fluoroquinolones which are as potent as or more potent than norfloxacin when administered orally and subcutaneously in mouse protection tests against Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. A-56619 and A-56620 were more potent than norfloxacin when administered orally against Escherichia coli, Proteus mirabilis, Serratia marcescens, and Pseudomonas aeruginosa. A-56620 was as potent or two- to threefold more potent than ...

  19. In vitro susceptibilities of mycoplasmas and ureaplasmas to new macrolides and aryl-fluoroquinolones.

    Waites, K B; Cassell, G. H.; Canupp, K C; Fernandes, P B

    1988-01-01

    In vitro activities of the new macrolides clarithromycin, previously designated A-56268 (TE-031), and A-63075 and of the aryl-fluoroquinolones difloxacin (A-56619) and temafloxacin (A-62254) against 14 strains of Mycoplasma pneumoniae, 20 strains of Mycoplasma hominis, and 28 strains of Ureaplasma urealyticum were compared with that of erythromycin. All three macrolides inhibited growth of M. pneumoniae at less than 0.125 micrograms/ml. No macrolide was active against M. hominis. For five str...

  20. Cu-catalyzed trifluoromethylation of aryl iodides with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide

    Yuzo Nakamura; Motohiro Fujiu; Tatsuya Murase; Yoshimitsu Itoh; Hiroki Serizawa; Kohsuke Aikawa; Koichi Mikami

    2013-01-01

    The trifluoromethylation of aryl iodides catalyzed by copper(I) salt with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide and Zn dust was accomplished. The catalytic reactions proceeded under mild reaction conditions, providing the corresponding aromatic trifluoromethylated products in moderate to high yields. The advantage of this method is that additives such as metal fluoride (MF), which are indispensable to activate silyl groups for transmetallation in the corresp...

  1. Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

    Rao, A Veera Bhadra

    2016-01-01

    Summary A facile and modular synthesis of triarylmethanes was achieved in good yield via a two-step sequence in which the final step is the copper(II)-catalyzed arylation of diarylmethanols with arylboronic acids. By using this protocol a variety of symmetrical and unsymmetrical triarylmethanes were synthesized. As an application of the newly developed methodology, we demonstrate a high-yielding synthesis of the triarylmethane intermediate towards an anti-breast-cancer drug candidate. PMID:27340442

  2. A mild and simple synthesis of N-aryl substituted toluenesulfamides under solvent-free conditions

    ZHAO Na; WANG Yu-lu

    2004-01-01

    N- aryl substituted benzenesulfamides are often used as heating-sensitive recording material1, thermal printing material2, sensitizer3 and developer4. Moreover, some of the benzenesulfamides have antifungal activities5. Many methods have been described for preparation of sulfamides. They are used to carry out in solvent8 or in solid phase condition9. These methods required solvent or solid support and even required heating or cooling. At the same time, the process of these methods is complex. Now we have developed a new method to prepare N-aryl substituted toluenesulfamides under solvent-free conditions.In recent years, solvent-free technology has gained popularity in organic synthesis. For instance,solidstate reaction and microwave reaction have received considerable attention. Solvent-free synthesis of amides has been reported10-11. This technology has many advantages such as high efficiency and selectivity, easy separation and environmental acceptability. All these merits are in accord with green chemistry's requirements of energy-saving, high efficiency and environmental benefits.In our paper, we used a simple and efficient method for preparing N-aryl substituted toluenesulfamides under solvent-free conditions, as a replacement for classic solvent, which gives many environmental benefits.All reactions were completed at room temperature by co-grinding in an agate mortar for 3-20min and the results are shown in Table 1.In conclusion, we have developed an efficient and convenient method of preparation N-aryl substituted toluenesulfamides in high yields. It symbols an improvement for synthesis of benzenesulfamides.

  3. Dichotomy in regioselectivity of Pd-catalyzed direct C-H arylation of protected uracils

    Čerňová, Miroslava; Hocek, Michal

    Praha : Institute of Organic Chemistry and Biochemistry AS CR, v. v. i., 2011 - (Hocek, M.), s. 314-316 ISBN 978-80-86241-37-1. - (Collection Symposium Series. 12). [ Chemistry of Nucleic Acid Components /15./. Český Krumlov (CZ), 05.06.2011-10.06.2011] R&D Projects: GA MŠk(CZ) LC06077 Institutional research plan: CEZ:AV0Z40550506 Keywords : direct C-H arylation * uracils * pyrimidines * palladium Subject RIV: CC - Organic Chemistry

  4. Palladium(II) Aryl-amido Complexes of Diphosphinoazines in Unsymmetrical PNP' Pincer-type Configuration

    Storch, Jan; Čermák, Jan; Pošta, Martin; Sýkora, Jan; Císařová, I.

    2008-01-01

    Roč. 693, č. 18 (2008), s. 3029-3034. ISSN 0022-328X R&D Projects: GA ČR GA203/01/0554; GA ČR GA203/06/0738; GA MŠk(CZ) LC06070 Institutional research plan: CEZ:AV0Z40720504 Keywords : diphosphinoazines * pincer complexes * aryl-amido complexes Subject RIV: CC - Organic Chemistry Impact factor: 1.866, year: 2008

  5. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles

    Hubbard, Troy D.; Murray, Iain A.; Bisson, William H.; Lahoti, Tejas S.; Krishne Gowda; Amin, Shantu G.; Patterson, Andrew D.; Perdew, Gary H.

    2015-01-01

    Ligand activation of the aryl hydrocarbon (AHR) has profound effects upon the immunological status of the gastrointestinal tract, establishing and maintaining signaling networks, which facilitate host-microbe homeostasis at the mucosal interface. However, the identity of the ligand(s) responsible for such AHR-mediated activation within the gut remains to be firmly established. Here, we combine in vitro ligand binding, quantitative gene expression, protein-DNA interaction and ligand structure ...

  6. Syntheses of light emitting poly(N-aryl-2,7-carbazole)s

    Recent remarkable development of poly(2,7-carbazole)s and copolymers including a carbazolyl unit have demonstrated that they are one of key conjugated polymer materials for optoelectronic applications. This short review reports recent progress made in synthesis and characterization of poly(N-aryl-2,7-carbazole)s for application of light emitting diode. Main strategy and remaining challenges in the development of reliable emitting materials for devices of organic light emitting diodes are discussed

  7. Extending the utility of [Pd(NHC(cinnamylCl] precatalysts: Direct arylation of heterocycles

    Anthony R. Martin

    2012-09-01

    Full Text Available The use of [Pd(NHC(cinnamylCl] precatalysts in the direct arylation of heterocycles has been investigated. Among four different precatalysts, [Pd(SIPr(cinnamylCl] proved to be the most efficient promoter of the reaction. The C–H functionalization of sulfur- or nitrogen-containing heterocycles has been achieved at low catalyst loadings. These catalyst charges range from 0.1 to 0.01 mol % palladium.

  8. Extending the utility of [Pd(NHC)(cinnamyl)Cl] precatalysts : Direct arylation of heterocycles

    Martin, Anthony R; Anthony Chartoire; Slawin, Alexandra M. Z.; Steven P. Nolan

    2012-01-01

    The use of [Pd(NHC)(cinnamyl)Cl] precatalysts in the direct arylation of heterocycles has been investigated. Among four different precatalysts, [Pd(SIPr)(cinnamyl)Cl] proved to be the most efficient promoter of the reaction. The C–H functionalization of sulfur- or nitrogen-containing heterocycles has been achieved at low catalyst loadings. These catalyst charges range from 0.1 to 0.01 mol % palladium.

  9. Synthesis of Poly(aryl ether ketone) Copolymers Containing Adamantyl-substituted Naphthalene Rings

    ZHU Xiao-liang; ZHANG Shu-ling; REN Dian-fu; GUAN Shao-wei; WANG Gui-bin; JIANG Zhen-hua

    2009-01-01

    @@ 1 Introduction High performance polymers have received considerable attention over the past decade owing to their increased demands as replacements for metals or ceramics in automotive,aerospace,and microelectronic industries.Poly(aryl ether ketone)s(PAEKs) are a class of important high-performance aromatic polymers with excellent mechanical properties,good solvent resistance,size-accuracy,electrical characteristics,and superior thermal stability[1-3].

  10. Inducibility of aryl hydrocarbon hydroxylase in BALB/c/ki mice exposed to urban air pollution.

    Mostardi, R A; Ely, D L; Liebelt, A; Grossman, S; Fu, M M

    1981-05-01

    In two separate experiments BALB/c/ki mice were exposed to urban air pollution. Mice exposed to clean air served as controls. In both experiments there were no obvious quantitative or qualitative differences in lung or liver tissue examined by light microscopy. In both experiments higher aryl hydrocarbon hydroxylase activities and higher trace metal concentrations were observed in the mice exposed to polluted urban air. These data are interpreted in terms of health hazards of urban air pollutants. PMID:7265310

  11. Inducibility of aryl hydrocarbon hydroxylase in BALB/c/Ki mice exposed to urban air pollution

    Mostardi, R.A. (Univ. of Akron, OH); Ely, D.L.; Liebelt, A.; Grossman, S.; Fu, M.M.

    1981-05-01

    In two separate experiments BALB/c/Kl mice were exposed to urban air pollution. Mice exposed to clean air served as controls. In both experiments there were no obvious quantitative or qualitative differences in lung or liver tissue examined by light microscopy. In both experiments higher aryl hydrocarbon hydroxylase activities and higher trace metal concentrations were observed in the mice exposed to polluted urban air. These data are interpreted in terms of health hazards of urban air pollutants.

  12. Synergistic Rhodium/Copper Catalysis: Synthesis of 1,3-Enynes and N-Aryl Enaminones.

    Wang, Nan-Nan; Huang, Lei-Rong; Hao, Wen-Juan; Zhang, Tian-Shu; Li, Guigen; Tu, Shu-Jiang; Jiang, Bo

    2016-03-18

    Synergistic rhodium/copper catalysis enables new three-component coupling reactions of terminal alkynes and α-diazoketones and/or arylamines, allowing dediazotized carbene C-H insertion for the synthesis of functionalized 1,3-enynes and N-aryl enaminones with high stereoselectivity. The synthetic utility of these transformations results in subsequent C-C or/and C-N bond-forming reactions to effectively build up functional molecules with potential significance. PMID:26987884

  13. Integrated catalysis opens new arylation pathways via regiodivergent enzymatic C–H activation

    Latham, Jonathan; Henry, Jean-Marc; Sharif, Humera H.; Menon, Binuraj R. K.; Shepherd, Sarah A; Greaney, Michael F; Micklefield, Jason

    2016-01-01

    Despite major recent advances in C–H activation, discrimination between two similar, unactivated C–H positions is beyond the scope of current chemocatalytic methods. Here we demonstrate that integration of regioselective halogenase enzymes with Pd-catalysed cross-coupling chemistry, in one-pot reactions, successfully addresses this problem for the indole heterocycle. The resultant ‘chemobio-transformation' delivers a range of functionally diverse arylated products that are impossible to acces...

  14. AHR2 Mutant Reveals Functional Diversity of Aryl Hydrocarbon Receptors in Zebrafish

    Goodale, Britton C.; La Du, Jane K; Bisson, William H.; Janszen, Derek B.; Waters, Katrina M.; Tanguay, Robert L.

    2012-01-01

    The aryl hydrocarbon receptor (AHR) is well known for mediating the toxic effects of TCDD and has been a subject of intense research for over 30 years. Current investigations continue to uncover its endogenous and regulatory roles in a wide variety of cellular and molecular signaling processes. A zebrafish line with a mutation in ahr2 (ahr2 hu3335), encoding the AHR paralogue responsible for mediating TCDD toxicity in zebrafish, was developed via Targeting Induced Local Lesions IN Genomes (TI...

  15. Replacing conventional carbon nucleophiles with electrophiles: nickel-catalyzed reductive alkylation of aryl bromides and chlorides.

    Everson, Daniel A; Jones, Brittany A; Weix, Daniel J

    2012-04-11

    A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (-OH, -NHTs, -OAc, -OTs, -OTf, -COMe, -NHBoc, -NHCbz, -CN, -SO(2)Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture. The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki-Miyaura, Stille, and Hiyama-Denmark reactions. Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R-X) and no reaction at the nucleophilic carbon (R-[M]) for organoboron (-Bpin), organotin (-SnMe(3)), and organosilicon (-SiMe(2)OH) containing organic halides (X-R-[M]). A Hammett study showed a linear correlation of σ and σ(-) parameters with the relative rate of reaction of substituted aryl bromides with bromoalkanes. The small ρ values for these correlations (1.2-1.7) indicate that oxidative addition of the bromoarene is not the turnover-frequency determining step. The rate of reaction has a positive dependence on the concentration of alkyl bromide and catalyst, no dependence upon the amount of zinc (reducing agent), and an inverse dependence upon aryl halide concentration. These results and studies with an organic reductant (TDAE) argue against the intermediacy of organozinc reagents. PMID:22463689

  16. Diastereoselective metal-catalyzed synthesis of C-aryl and C-vinyl glycosides.

    Nicolas, Lionel; Angibaud, Patrick; Stansfield, Ian; Bonnet, Pascal; Meerpoel, Lieven; Reymond, Sébastien; Cossy, Janine

    2012-10-29

    Cobalt, the catalyst of choice: The diastereoselective cobalt-catalyzed cross-coupling of 1-bromo glycosides and aryl or vinyl Grignard reagents is described. A convenient and inexpensive catalyst, [Co(acac)(3)]/tmeda (acac = acetylacetonate, tmeda = N,N'-tetramethylethylenediamine), gives full α selectivity in the mannose and galactose series, and an α selectivity in the glucose series with α/β ratios of 1.3:1-3:1. PMID:23023954

  17. Nickel-Catalyzed Regiodivergent Opening of Epoxides with Aryl Halides: Co-Catalysis Controls Regioselectivity

    Zhao, Yang; Weix, Daniel J.

    2013-01-01

    Epoxides are versatile intermediates in organic synthesis, but have rarely been employed in cross-coupling reactions. We report that bipyridine-ligated nickel can mediate the addition of functionalized aryl halides, a vinyl halide, and a vinyl triflate to epoxides under reducing conditions. For terminal epoxides, the regioselectivity of the reaction depends upon the co-catalyst employed. Iodide co-catalysis results in opening at the less hindered position via an iodohydrin intermediate. Titan...

  18. Purification and enzymatic characterization of secretory glycoside hydrolase family 3 (GH3) aryl β-glucosidases screened from Aspergillus oryzae genome.

    Kudo, Kanako; Watanabe, Akira; Ujiie, Seiryu; Shintani, Takahiro; Gomi, Katsuya

    2015-12-01

    By a global search of the genome database of Aspergillus oryzae, we found 23 genes encoding putative β-glucosidases, among which 10 genes with a signal peptide belonging to glycoside hydrolase family 3 (GH3) were overexpressed in A. oryzae using the improved glaA gene promoter. Consequently, crude enzyme preparations from three strains, each harboring the genes AO090038000223 (bglA), AO090103000127 (bglF), and AO090003001511 (bglJ), showed a substrate preference toward p-nitrophenyl-β-d-glucopyranoside (pNPGlc) and thus were purified to homogeneity and enzymatically characterized. All the purified enzymes (BglA, BglF, and BglJ) preferentially hydrolyzed aryl β-glycosides, including pNPGlc, rather than cellobiose, and these enzymes were proven to be aryl β-glucosidases. Although the specific activity of BglF toward all the substrates tested was significantly low, BglA and BglJ showed appreciably high activities toward pNPGlc and arbutin. The kinetic parameters of BglA and BglJ for pNPGlc suggested that both the enzymes had relatively higher hydrolytic activity toward pNPGlc among the fungal β-glucosidases reported. The thermal and pH stabilities of BglA were higher than those of BglJ, and BglA was particularly stable in a wide pH range (pH 4.5-10). In contrast, BglJ was the most heat- and alkaline-labile among the three β-glucosidases. Furthermore, BglA was more tolerant to ethanol than BglJ; as a result, it showed much higher hydrolytic activity toward isoflavone glycosides in the presence of ethanol than BglJ. This study suggested that the mining of novel β-glucosidases exhibiting higher activity from microbial genome sequences is of great use for the production of beneficial compounds such as isoflavone aglycones. PMID:25936960

  19. Design, Synthesis, Characterization and Anticancer Prope rties of Novel 2-Chloro- N -(Aryl Substituted Acetamide Derivatives of 5-[2-(4- Methoxyphenyl Pyridin-3-yl]-1, 3, 4-Oxadiazole-2-Thiol

    Adimule Vinayak

    2014-12-01

    Full Text Available In this linear synthesis, novel different 2-chloro N-aryl substitutedacetamide derivatives of 5-[2-(4-methoxyphenyl pyridin-3-yl]-1, 3, 4-oxadiazole-2-thiol have been synthesized and screened for their cytotoxicity on PANC-1, HepG2and MCF7cell lines and obtained the IC50and CC50values.All the synthesized compounds were characterized by LCMS, IR, 1H and 13C (proton and Carbon 13 spectroscopies and elemental analysis. These compounds were evaluated for invitroanticancer activity on three different human leukemic cell lines, namely PANC-1,HepG2and MCF7.In total five compounds were synthesized and studied for their MTT assay. Among five synthesized novel compounds, the compound N-[5-(4-Methoxy-phenyl-pyridin-2-yl]-2-{5-[2-(4-methoxy-phenyl-pyridin-3-yl][1,3,4]oxadiazol-2 ylsulfanyl}-acetamide6eis highly cytotoxic on PANC-1and HepG2cell lines having IC50of 4.6μM and 2.2μM respectively whereas the compound 6cis moderately cytotoxic on MCF7having IC5015.5μM respectively. Rest all the compounds showed less cytotoxicity on all the three cell lines as compared with the standard 5-FU.

  20. Adsorption of sodium alkyl aryl sulfonates on sandstone. [Berea and Benton Tar Springs sandstones

    Lawson, J.B.; Dilgren, R.E.

    1976-01-01

    Equilibrium adsorption isotherms of commercial alkyl aryl sulfonates (petroleum sulfonates), and pure alkyl aryl sulfonates on disaggregated Berea and Benton Tar Springs sandstones were determined. Adsorption isotherms of commercial sulfonates were found to contain maxima, which did not necessarily correspond to the measured C.M.C. At adsorption maxima, surface coverage corresponded to about one half monomolecular layer of sulfonate, but, at high surfactant concentrations, coverage sometimes amounted to only about one-tenth of a monolayer. Pure alkyl aryl sulfonates were synthesized and adsorption on sandstone determined. These materials were found to yield conventional adsorption isotherms, with adsorption plateaus at about one half a monolayer of surface coverage. Apparently, adsorption maxima are unique to impure sulfonates. Selectivity of adsorption with respect to molecular weight and structural type was studied. Structure of petroleum sulfonate and accompanying mineral oil was determined as were structures of sulfonate and mineral oil that had been equilibrated with sandstone. Comparison showed no selectivity of adsorption based on carbon number distribution or structural type. However, aggregates relatively rich in mineral oil were found to be selectively adsorbed.

  1. Chiral 6-aryl-furo[2,3-d]pyrimidin-4-amines as EGFR inhibitors.

    Han, Jin; Kaspersen, Svein Jacob; Nervik, Sondre; Nørsett, Kristin G; Sundby, Eirik; Hoff, Bård Helge

    2016-08-25

    Epidermal growth factor receptor inhibitors are of importance in cancer therapy and possibly in the management of pain. Herein, we report a structure-activity relationship study with 29 new 6-aryl-furo[2,3-d]pyrimidin-4-amines, involving modification of the 4-amino group and 6-aryl function. The EGFR activity was especially dependent on having a chiral 4-benzylamino group with correct stereochemistry. Molecular dynamics indicate this to be due to favourable cation-π interactions. The most active inhibitor identified, equipotent to Erlotinib, was substituted with (R)-1-phenylethylamine at C-4 and a N(1), N(1)-dimethyl-1,2-diamine group in para position of the 6-aryl moiety. These new furopyrimidines had a different off-target kinase profile when compared to Erlotinib, and also possessed high activity towards Ba/F3 EGFR(L858R) reporter cells. Further, comparing the EGFR data of the furo[2,3-d]pyrimidin-4-amines with that of the corresponding thieno- and pyrrolopyrimidines concludes the furopyrimidine scaffold to be highly useful for development of new epidermal growth factor receptor antagonists. PMID:27235841

  2. General Copper-Catalyzed Coupling of Alkyl-, Aryl-, and Alkynylaluminum Reagents with Organohalides.

    Shrestha, Bijay; Thapa, Surendra; Gurung, Santosh K; Pike, Ryan A S; Giri, Ramesh

    2016-02-01

    We report the first example of a very general Cu-catalyzed cross-coupling of organoaluminum reagents with organohalides. The reactions proceed for the couplings of alkyl-, aryl-, and alkynylaluminum reagents with aryl and heteroaryl halides and vinyl bromides, affording the cross-coupled products in good to excellent yields. Both primary and secondary alkylaluminum reagents can be utilized as organometallic coupling partners. These reactions are not complicated by β-hydride elimination, and as a result rearranged products are not observed with secondary alkylaluminum reagents even for couplings with heteroaryl halides under "ligand-free" conditions. Radical clock experiment with a radical probe and relative reactivity study of Ph3Al with two haloarenes, 1-bromonaphthalene and 4-chlorobenzonitrile, having two different redox potentials indicates that the reaction does not involve free aryl radicals and radical anions as intermediates. These results combined with the result of the Hammett plot obtained by reacting Ph3Al with iodoarenes containing p-H, p-Me, p-F, and p-CF3 substituents, which shows a linear curve (R(2) = 0.99) with a ρ value of +1.06, suggest that the current transformation follows an oxidative addition-reductive elimination pathway. PMID:26735748

  3. Preparation of 5-Aryl-2-Alkyltetrazoles with Aromatic Aldehydes, Alkylhydrazine, Di-tert-butyl Azodicarboxylate, and [Bis(trifluoroacetoxy)iodo]benzene.

    Imai, Taro; Harigae, Ryo; Moriyama, Katsuhiko; Togo, Hideo

    2016-05-01

    A variety of 5-aryl-2-methyltetrazoles and 5-aryl-2-benzyltetrazoles were directly prepared in good to moderate yields by the reaction of aromatic aldehydes with methylhydrazine and benzylhydrazine, followed by treatment with di-tert-butyl azodicarboxylate and [bis(trifluoroacetoxy)iodo]benzene in a mixture of dichloromethane and 2,2,2-trifluoroethanol at room temperature. The present method is a novel one-pot preparation of 5-aryl-2-methyltetrazoles and 5-aryl-2-benzyltetrazoles through a [2N + 2N] combination under transition metal-free and mild conditions. PMID:27078200

  4. Synthesis of N-Aryl-2-allyl Pyrrolidines via Palladium-catalyzed Carboamination Reactions of γ-(N-Arylamino)alkenes with Vinyl Bromides

    Ney, Joshua E.; Hay, Michael B.; Yang, Qifei; Wolfe, John P.

    2005-01-01

    A palladium-catalyzed carboamination reaction of γ-N-arylamino alkenes with vinyl bromides that affords N-aryl-2-allyl pyrrolidines is described. These reactions proceed with high diastereoselectivity for the formation of trans-2,3- and cis-2,5-disubstituted pyrrolidines. Conditions for a tandem N-arylation/carboamination sequence that leads to the formation of an N-aryl-2-allyl pyrrolidine or indoline via the coupling of a primary γ-amino alkene, an aryl bromide, and a vinyl bromide are also...

  5. THE IMPACT OF PHTHALATE ESTERS IN THE ENVIRONMENTAL AND HUMAN HEALTH – ARE THESE COMPOUNDS, A NECESSARY EVIL?

    DOS SANTOS, Marcel Silveira

    2011-01-01

    Phthalates are a group of diesters of phthalic acid (dialkyl or alkyl aryl esters of 1,2-benzenedicarboxylic acid) and they are primarily used as plasticizers (substances added to plastics to increase their flexibility). As the phthalates are not chemically bonded to the polymer, these compounds can migrate from the plastic material to the environment and, consequently, they are found in food, water, soil, air and in the human body. This article discusses the problem of using those compoun...

  6. Standard molar volumes and expansibilities of 1,3-alkyl-N-substituted achiral glycolurils in water at T = (278.15 to 318.15) K and p = 0.1 MPa: A comparative analysis

    Highlights: • Densities of aqueous 1,3-dimethylglycoluril and 1,3-diethylglycoluril were measured. • Densimetric measurements were carried out at T = (278.15 to 318.15) K and ∼0.1 MPa. • Standard molar volumes and expansibilities of glycolurils in water were derived. • 1,3-DMGU has the more pronounced ability to hydrogen-bonding with water molecules. • Tendency to structure-loosening in aqueous solution increases going to 1,3-DEGU. - Abstract: Densities of aqueous solutions of achiral 1,3-dimethylglycoluril (1,3-DMGU) and 1,3-diethylglycoluril (1,3-DEGU) were measured using a hermetically sealed vibrating-tube densimeter, with an uncertainty of 1 · 10−5 g · cm−3, at T = (278.15, 288.15, 298.15, 308.15, and 318.15) K and p = (99.6 ± 0.8) kPa. The solute molality was ranged from (0.06 to 0.39) and from (0.01 to 0.07) mol · kg−1 for the aqueous 1,3-DMGU and 1,3-DEGU, respectively. The standard (at infinite dilution) molar volumes and isobaric expansibilities for the 1,3-dialkyl-N-substituted glycolurils compared in water were calculated and discussed in comparison with the previously derived molar enthalpies and heat capacities of their dissolution (hydration). The temperature-dependent behavior of packing-related hydration effects was described taking into account the structural features of a solute molecule

  7. Design and optimization of (3-aryl-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-ones as potent PLK4 inhibitors with oral antitumor efficacy.

    Li, Sze-Wan; Liu, Yong; Sampson, Peter B; Patel, Narendra Kumar; Forrest, Bryan T; Edwards, Louise; Laufer, Radoslaw; Feher, Miklos; Ban, Fuqiang; Awrey, Donald E; Hodgson, Richard; Beletskaya, Irina; Mao, Guodong; Mason, Jacqueline M; Wei, Xin; Luo, Xunyi; Kiarash, Reza; Green, Erin; Mak, Tak W; Pan, Guohua; Pauls, Henry W

    2016-10-01

    Previous efforts from our laboratory demonstrated that (E)-3-((3-(E)-vinylaryl)-1H-indazol-6-yl)methylene)-indolin-2-ones are potent PLK4 inhibitors with in vivo anticancer efficacy upon IP dosing. As part of a continued effort to develop selective and orally efficacious inhibitors, we examined variations on this theme wherein 'directly-linked' aromatics, pendant from the indazole core, replace the arylvinyl moiety. Herein, we describe the design and optimization of this series which was ultimately superseded by (3-aryl-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-ones. The latter compounds are potent and selective inhibitors of PLK4 with oral exposure in rodents and in vivo anticancer activity. Compound 13b, in particular, has a bioavailability of 22% and achieved a 96% tumor growth inhibition in an MDA-MB-468 xenograft study. PMID:27592744

  8. Intermetallic Compounds

    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-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 σ.

  9. BippyPhos: a single ligand with unprecedented scope in the Buchwald-Hartwig amination of (hetero)aryl chlorides.

    Crawford, Sarah M; Lavery, Christopher B; Stradiotto, Mark

    2013-12-01

    Over the past two decades, considerable attention has been given to the development of new ligands for the palladium-catalyzed arylation of amines and related NH-containing substrates (i.e., Buchwald-Hartwig amination). The generation of structurally diverse ligands, by research groups in both academia and industry, has facilitated the accommodation of sterically and electronically divergent substrates including ammonia, hydrazine, amines, amides, and NH heterocycles. Despite these achievements, problems with catalyst generality persist and access to multiple ligands is necessary to accommodate all of these NH-containing substrates. In our quest to address this significant limitation we identified the BippyPhos/[Pd(cinnamyl)Cl]2 catalyst system as being capable of catalyzing the amination of a variety of functionalized (hetero)aryl chlorides, as well as bromides and tosylates, at moderate to low catalyst loadings. The successful transformations described herein include primary and secondary amines, NH heterocycles, amides, ammonia and hydrazine, thus demonstrating the largest scope in the NH-containing coupling partner reported for a single Pd/ligand catalyst system. We also established BippyPhos/[Pd(cinnamyl)Cl]2 as exhibiting the broadest demonstrated substrate scope for metal-catalyzed cross-coupling of (hetero)aryl chlorides with NH indoles. Furthermore, the remarkable ability of BippyPhos/[Pd(cinnamyl)Cl]2 to catalyze both the selective monoarylation of ammonia and the N-arylation of indoles was exploited in the development of a new one-pot, two-step synthesis of N-aryl heterocycles from ammonia, ortho-alkynylhalo(hetero)arenes and (hetero) aryl halides through tandem N-arylation/hydroamination reactions. Although the scope in the NH-containing coupling partner is broad, BippyPhos/[Pd(cinnamyl)Cl]2 also displays a marked selectivity profile that was exploited in the chemoselective monoarylation of substrates featuring two chemically distinct NH

  10. Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents

    Maher A. El-Hashash

    2015-12-01

    Full Text Available A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923, (ATCC 10987, (ATCC 274, and (SM514. The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data.

  11. Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents.

    El-Hashash, Maher A; Rizk, Sameh A; Atta-Allah, Saad R

    2015-01-01

    A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data. PMID:26690393

  12. Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability.

    Żołnowska, Beata; Sławiński, Jarosław; Pogorzelska, Aneta; Szafrański, Krzysztof; Kawiak, Anna; Stasiłojć, Grzegorz; Belka, Mariusz; Ulenberg, Szymon; Bączek, Tomasz; Chojnacki, Jarosław

    2016-01-01

    A series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 27-60 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell lines HCT-116, HeLa and MCF-7, with IC50 values below 100 μM. It was found that for the analogues 36-38 the naphthyl moiety contributed significantly to the anticancer activity. Cytometric analysis of translocation of phosphatidylserine as well as mitochondrial membrane potential and cell cycle revealed that the most active compounds 37 (HCT-116 and HeLa) and 46 (MCF-7) inhibited the proliferation of cells by increasing the number of apoptotic cells. Apoptotic-like, dose dependent changes in morphology of cell lines were also noticed after treatment with 37 and 46. Moreover, triazines 37 and 46 induced caspase activity in the HCT-116, HeLa and MCF-7 cell lines. Selected compounds were tested for metabolic stability in the presence of pooled human liver microsomes and NADPH, both R² and Ar = 4-CF₃-C₆H₄ moiety in 2-(R²-methylthio)-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides simultaneously increased metabolic stability. The results pointed to 37 as a hit compound with a good cytotoxicity against HCT-116 (IC50 = 36 μM), HeLa (IC50 = 34 μM) cell lines, apoptosis-inducing activity and moderate metabolic stability. PMID:27338337

  13. Compound odontoma

    José Marcelo Vargas Pinto

    2008-01-01

    Full Text Available Odontomas are the most common types of odontogenic tumors, as they are considered more as a developmental anomaly (hamartoma than as a true neoplasia. The aim of the present study is to describe a clinical case of compound odontoma, analyzing its most commonsigns, its region of location, the decade of life and patient’s gender, disorders that may occur as well as the treatment proposed. In order to attain this objective, the method was description of the present clinical case and bibliographic revision, arriving at the result that the treatment for this type of lesion invariably is surgical removal (enucleation and curettage and the prognosis is excellent. The surgical result was followed up in the post-operative period by radiographic exam, and it was possible to conclude that there was complete cicatrization and tissue repair.

  14. Synthesis, Central Nervous System Activity and Structure-Activity Relationships of Novel 1-(1-Alkyl-4-aryl-4,5-dihydro-1H-imidazo-3-substituted Urea Derivatives

    Elżbieta Szacoń

    2015-02-01

    Full Text Available A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a–3h were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a and 1b and appropriate benzyl-, phenethyl-isocyanate or ethyl 4-isocyanatobenzoate and ethyl isocyanatoacetate 2 in dichloromethane. Derivatives 4c and 4g resulted from the conversion of 3c and 3g into the respective amides due to action of an aqueous ammonia solution. The results obtained in this study, based on literature data suggest a possible involvement of serotonin system and/or the opioid system in the effects of tested compounds, and especially in the effect of compound 3h. The best activity of compound 3h may be primarily attributed to its favourable ADMET properties, i.e., higher lipophilicity (related to lower polar surface area and greater molecular surface, volume and mass than for other compounds and good blood-brain permeation. This compound has also the greatest polarizability and ovality. The HOMO and LUMO energies do not seem to be directly related to activity.

  15. Design, synthesis and evaluation of 6-aryl-indenoisoquinolone derivatives dual targeting ERα and VEGFR-2 as anti-breast cancer agents.

    Tang, Zhichao; Wu, Chengzhe; Wang, Tianlin; Lao, Kejing; Wang, Yejun; Liu, Linyi; Muyaba, Moses; Xu, Pei; He, Conghui; Luo, Guoshun; Qian, Zhouyang; Niu, Shaoxiong; Wang, Lijun; Wang, Ying; Xiao, Hong; You, Qidong; Xiang, Hua

    2016-08-01

    The estrogen receptors have played important roles in breast cancer development and progression. Selective estrogen receptor modulators, such as Tamoxifen, have showed great benefits in the treatment and prevention of breast cancer. But the disadvantages of induction of endometrial cancer and drug resistance have limited their use. Multiple ligand which act at multiple biomolecular targets may exert favorable advantages of improved efficacy with lower incidence of side effects. In this work, we described the synthesis and evaluation of a series of 6-aryl-indenoisoquinolone derivatives as dual ERα and VEGFR-2 inhibitors. These compounds presented good ERα binding affinity and ERα antagonistic activity, as well as potent VEGFR-2 inhibitory potency. They also possessed excellent anti-proliferative activities against MCF-7, MDA-MB-231, Ishikawa and HUVEC cell lines. Further investigation of selective compound 21c showed that it was able to inhibit the activation of VEGFR-2 and the signaling transduction of Raf-1/MAPK/ERK pathway in MCF-7 cells. PMID:27176944

  16. Kinetico-mechanistic studies on the formation of seven-membered [C,N]-platinacycles: the effect of methyl or fluoro substituents on the aryl ancillary ligands.

    Crespo, Margarita; Font-Bardia, Mercè; Martínez, Manuel

    2015-12-01

    The reactions of dinuclear [Pt2(4-RC6H4)4(μ-SEt2)2] (R = Me or F), or mononuclear [Pt(4-RC6H4)2(SMe2)2] (R = Me or H), platinum(ii) compounds with imines of the general formula 2-X,6-YC6H3CH[double bond, length as m-dash]NCH2Ph (X = Br, Y = F; X = Cl, Y = F; X = Br, Y = H) produced seven-membered [C,N]-platinacycles. The reaction consists of the initial formation of cyclometallated platinum(iv) compounds followed by a three step process: reductive elimination, isomerisation of the resulting non-cyclometallated intermediate and a final cycloplatination process. Combined (1)H NMR and UV-Vis kinetico-mechanistic studies indicated that the rate determining step of the process depends on the nature of the aryl-Pt ligand (phenyl, p-tolyl or p-fluorophenyl). PMID:26158624

  17. Theoretical evaluation of medicinal properties for some of N-aryl-3-hydroxypyridine-4-ones derivative compounds

    Mohsen Oftadeh

    2014-02-01

    Full Text Available Nowadays, the bidentate ligands 3-hydroxypyridin-4-ones (HPOs as orally active iron chelating agents have been demonstrated to possess potentials for the treatment of some of the human diseases such as iron-overload in thalassaemia patients and malaria. In this research, a series of HPOs with different substitutes and positions were theoretically investigated in order to extract and predict their partition coefficient values (LogP which were experimentally determined in an aqueous/octanol system. The effective electronic parameters on logP were also investigated. The results show that the type of method, basis set, and the solvent do not basically affect on the logP values. But some parameters such as hydrophobicity, polarizability, and orbital electronic charge density (HOMO and LUMO are effective on logP values.

  18. Synthesis of 2,3-epoxy-1-phenyl-3-aryl-1-propanone by combination of phase transfer catalyst and ultrasound irradiation

    Ji-Tai Li

    2009-03-01

    Full Text Available Seven 2,3-epoxy-1-phenyl-3-aryl-1-propanones were synthesized via epoxidation of thecorresponding 1-phenyl-3-aryl-2-propen-1-ones with 30% aqueous hydrogen peroxide in 74-99% yields usingbenzyldimethyltetradecylammonium chloride as phase transfer catalyst under ultrasound irradiation.

  19. Intramolecular 1,5-H transfer reaction of aryl iodides through visible-light photoredox catalysis: a concise method for the synthesis of natural product scaffolds.

    Chen, Jian-Qiang; Wei, Yun-Long; Xu, Guo-Qiang; Liang, Yong-Min; Xu, Peng-Fei

    2016-05-11

    The intramolecular 1,5-H transfer reaction of the aryl radicals generated from unactivated aryl iodides by photocatalysis is described. The features of this transformation are operational simplicity, excellent yields, mild reaction conditions, and good functional group tolerance. With this approach, a more concise formal synthesis of (±)-coerulescine and (±)-physovenine is accomplished. PMID:27100267

  20. Application of nano SnO2 as a green and recyclable catalyst for the synthesis of 2-aryl or alkylbenzoxazole derivatives under ambient temperature

    Seyed Mohammad Vahdat; Shima Ghafouri Raz; Saeed Baghery

    2014-05-01

    Application of nano SnO2 as an efficient and benign catalyst has been explored for the synthesis of 2-aryl or alkylbenzoxazole derivatives via condensation reaction of aldehyde with 2-aminophenol. The reactions proceed under heterogeneous and mild conditions in ethanol at room temperature to provide 2-aryl or alkylbenzoxazoles in high yields.

  1. Synthesis of N1-Substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyra- zolethiocarboxamide as Novel Small Molecule Inhibitors of Cysteine Protease of T. cruzi

    2002-01-01

    A series of N1-substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyrazolethiocarboxamide were prepared from the Mannich bases of aryl ketones in good yields. Some derivatives were found to be active against the cysteine protease of T.cruzi..

  2. High-resolution laser spectroscopy and magnetic effect of the B{sup ~2}E{sup ′}←X{sup ~2}A{sub 2}{sup ′} transition of the {sup 15}N substituted nitrate radical

    Tada, Kohei; Teramoto, Kanon [Graduate School of Science, Kobe University, Kobe 657-8501 (Japan); Ishiwata, Takashi [Graduate School of Information Sciences, Hiroshima City University, Hiroshima 731-3194 (Japan); Hirota, Eizi [The Graduate University for Advanced Studies, Kanagawa 240-0193 (Japan); Kasahara, Shunji, E-mail: kasha@kobe-u.ac.jp [Graduate School of Science, Kobe University, Kobe 657-8501 (Japan); Molecular Photoscience Research Center, Kobe University, Kobe 657-8501 (Japan)

    2015-03-21

    Rotationally resolved high-resolution fluorescence excitation spectra of the 0–0 band of the B{sup ~2}E{sup ′}←X{sup ~2}A{sub 2}{sup ′} transition of the {sup 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{sup −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{sup −1} spacing were assigned to the transitions from the X{sup ~2}A{sub 2}{sup ′} (υ″ = 0, k″ = 0, N″ = 1, J″ = 0.5 and 1.5) to the {sup 2}E{sub 3/2}{sup ′} (J′ = 1.5), {sup 2}E{sub 1/2}{sup ′} (J′ = 0.5), and {sup 2}E{sub 1/2}{sup ′} (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{sup ~2}E{sup ′} (υ = 0) state and surrounding dark vibronic states. Some series of rotational lines other than those from the X{sup ~2}A{sub 2}{sup ′} (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{sup ~2}E{sub 1/2}{sup ′} (υ = 0) state were estimated by a deperturbed analysis to be T{sub 0} = 15 098.20(4) cm{sup −1}, B = 0.4282(7) cm{sup −1}, and D{sub J} = 4 × 10{sup −4} cm{sup −1}. In the observed region, both the {sup 2}E{sub 1/2}{sup ′} and {sup 2}E{sub 3/2}{sup ′} spin-orbit components were identified, and the spin-orbit interaction constant of the B{sup ~2}E{sup ′} (υ = 0) state was estimated to be −12 cm{sup −1} as the lower limit.

  3. 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

    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), 1H and 13C 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)

  4. Copper-Catalyzed Three-Component Reaction for Regioselective Aryl- and Heteroarylselenation of Indoles using Selenium Powder.

    Luo, Dongping; Wu, Ge; Yang, Hang; Liu, Miaochang; Gao, Wenxia; Huang, Xiaobo; Chen, Jiuxi; Wu, Huayue

    2016-06-01

    A new and efficient copper-catalyzed C3 aryl- and heteroarylselenation of indoles employing selenium powder has been developed. The advantages of this chemistry involve the use of cheap selenating reagents, tolerance of a variety of functional groups, and practicality. In addition, this protocol has been further elaborated in an intramolecular phenylselenation of a (hetero) aryl C-H bond to construct an important motif of benzoselenopheno[3,2-b]indole. A preliminary mechanism study suggests that the reaction starts with a Ullman-type selenation between aryl iodides and selenium, followed by an oxidative cross-coupling with indole. The utility of this method has been demonstrated in an efficient gram-scale synthesis and an application to the synthesis of tubulin polymerization inhibitor. PMID:27191713

  5. Recyclable heterogeneous copper oxide on alumina catalyzed coupling of phenols and alcohols with aryl halides under ligand-free conditions.

    Swapna, Kokkirala; Murthy, Sabbavarapu Narayana; Jyothi, Mocharla Tarani; Nageswar, Yadavalli Venkata Durga

    2011-09-01

    An efficient alumina-supported CuO-catalyzed O-arylation of phenols and aliphatic alcohols with various aryl as well as heteroaryl halides under ligand-free conditions are reported. This protocol provides a variety of diaryl ether and bis-diaryl ether motifs by reacting different aryl/aliphatic halides with differently substituted phenols and saturated alcohols in the presence of a catalytic amount of CuO on alumina and KOH as a base at moderate temperature under nitrogen atmosphere. The described methodology is simple, straightforward and efficient to afford the cross-coupled products in high yields under ligand-free conditions. The explored catalyst is inexpensive, air-stable and recyclable up to three cycles. PMID:21695321

  6. Palladium-catalyzed direct desulfitative C2 arylations of 3-halo-N-protected indoles using (hetero)arenesulfonyl chlorides.

    Hfaiedh, Anoir; Ben Ammar, Hamed; Soulé, Jean-François; Doucet, Henri

    2016-06-01

    The direct arylation of N-protected 3-haloindole derivatives with benzenesulfonyl chlorides as coupling partners using 5 mol% of bis(acetonitrile)dichloropalladium(ii) catalyst and lithium carbonate as a base in 1,4-dioxane was investigated. We demonstrated that both iodo and chloro substituents at the indolyl C3 position act as temporary blocking groups allowing the formation of 2-arylindoles through a direct desulfitative arylation, followed by in situ dehalogenation. While, from 3-bromoindole derivatives, 2-aryl-3-bromoindoles were obtained without debromination, and could be converted into 2,3-diarylindoles through a second palladium coupling. This method allows one to prepare in a few steps a very wide variety of indole derivatives, which are of interest in the synthesis of bioactive molecules. PMID:27171489

  7. A novel role of the aryl hydrocarbon receptor (AhR in centrosome amplification - implications for chemoprevention

    Chatterjee Payel

    2010-06-01

    Full Text Available Abstract Background Centrosome aberrations can cause genomic instability and correlate with malignant progression in common human malignancies such as breast and prostate cancer. Deregulation of cyclin/cyclin-dependent kinase 2 (CDK2 activity has previously been shown to be critically involved in centrosome overduplication. We therefore test here whether small molecule CDK inhibitors derived from the bis-indole indirubin can be used to suppress centrosome aberrations as a novel approach to chemoprevention of malignant progression. Results As expected, we found that the CDK inhibitor indirubin-3'-oxime (IO suppresses centrosome amplification in breast cancer cells. However, we made the unexpected discovery that indirubin-derived compounds that have been chemically modified to be inactive as kinase inhibitors such as 1-methyl-indirubin-3'-oxime (MeIO still significantly reduced centrosome amplification. All indirubins used in the present study are potent agonists of the aryl hydrocarbon receptor (AhR, which is known for its important role in the cellular metabolism of xenobiotics. To corroborate our results, we first show that the coincidence of nuclear AhR overexpression, reflecting a constitutive activation, and numerical centrosome aberrations correlates significantly with malignancy in mammary tissue specimens. Remarkably, a considerable proportion (72.7% of benign mammary tissue samples scored also positive for nuclear AhR overexpression. We furthermore provide evidence that continued expression of endogenous AhR is critical to promote centriole overduplication induced by cyclin E and that AhR and cyclin E may function in the same pathway. Overexpression of the AhR in the absence of exogenous ligands was found to rapidly disrupt centriole duplication control. Nonetheless, the AhR agonists IO and MeIO were still found to significantly reduce centriole overduplication stimulated by ectopic AhR expression. Conclusions Our results indicate that

  8. Synthesis of N-aryl imidazoles catalyzed by copper nanoparticles on nanosized silica-coated maghemite

    Nador, Fabiana; Volpe, María A.; Alonso Valdés, Francisco; Radivoy, Gabriel

    2014-01-01

    A magnetically recoverable catalyst consisting of copper nanoparticles (CuNPs) on nanosized silica-coated maghemite is presented. The catalyst has been prepared under mild conditions by mixing the magnetic support with a freshly prepared suspension of CuNPs obtained by fast reduction of anhydrous CuCl2 with lithium sand and a catalytic amount of DTBB (4,4′-di-tert-butylbiphenyl) as electron carrier. This copper-based catalyst has shown to be very efficient in the N-(hetero)arylation of imidaz...

  9. Clean and fast cross-coupling of aryl halides in one-pot

    Valerica Pandarus

    2014-04-01

    Full Text Available Unsymmetrically coupled biaryls are synthesized in high yield starting from different aryl bromides and bis(pinacolatodiboron by carrying out the Miyaura borylation reaction followed by the Suzuki–Miyaura reaction in the same reaction pot over 1–2 mol % SiliaCat DPP-Pd. The SiliaCat DPP-Pd catalyst is air-stable and the method does not require the use of inert conditions. The use of non-toxic isopropanol or 2-butanol as reaction solvent further adds to the environmental benefits of this new green synthetic methodology.

  10. Nickel-Catalyzed Methylation of Aryl Halides with Deuterated Methyl Iodide.

    Hu, Lu; Liu, Xin; Liao, Xuebin

    2016-08-01

    A nickel-catalyzed methylation of aryl halides with cheap and readily available CH3 I or CD3 I is described. The reaction is applicable to a wide range of substrates and allows installation of a CD3 group under mild reaction conditions without deuterium scrambling to other carbon atoms. Initial mechanistic studies on the stoichiometric and catalytic reactions of the isolated [(dppp)Ni(C6 H4 -4-CO2 Et)Br] [dppp=1,3-bis(diphenylphosphanyl)propane] suggest that a Ni(0) /Ni(II) catalytic cycle is favored. PMID:27381725

  11. Copper Complexes of Anionic Nitrogen Ligands in the Amidation and Imidation of Aryl Halides

    Tye, Jesse W.; Weng, Zhiqiang; Johns, Adam M.; Incarvito, Christopher D.; Hartwig, John F.

    2008-01-01

    Copper(I) imidate and amidate complexes of chelating N,N-donor ligands, which are proposed intermediates in copper-catalyzed amidations of aryl halides, have been synthesized and characterized by X-ray diffraction and detailed solution-phase methods. In some cases, the complexes adopt neutral, three-coordinate trigonal planar structures in the solid state, but in other cases they adopt an ionic form consisting of an L2Cu+ cation and a CuX2− anion. A tetraalkylammonium salt of the CuX2− anion ...

  12. Synthesis and Preliminary Properties of Novel Poly(aryl ethers Containing β-Naphthalene Pendant Group

    L. Wang

    2014-01-01

    Full Text Available Two novel poly(aryl ethers containing β-naphthalene pendant group were synthesized and the structures of these polymers were confirmed by 1HNMR spectroscopy. The polymers exhibited good thermal stabilities with high Tg of 256°C and 274°C, respectively. The polymers are soluble in common organic solvents, such as DMAc, DMSO, CH2Cl2, and CHCl3, and can be electrospun into microfiber (1–5 µm with lots of nanopores (<100 nm from CHCl3 solution. These fibers showed high hydrophobicity, and the contact angle of fibers is above 120°.

  13. Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen receptor alpha at human promoters

    Ahmed, Shaaima; Valen, Eivind; Sandelin, Albin Gustav;

    2009-01-01

    Recent studies have shown that activated aryl hydrocarbon receptor (AHR) induced the recruitment of estrogen receptor- (ER ) to AHR-regulated genes and that AHR is recruited to ER -regulated genes. However, these findings were limited to a small number of well-characterized AHR- or ER -responsive...... ER to AHR target genes but also that AHR is recruited to estrogen-responsive regions in a gene-specific manner, suggesting that AHR utilizes both of these mechanisms to modulate estrogen-dependent signaling....

  14. Synthesis and characterization of 4-aryl-4H-chromenes from H-cardanol.

    Rao, Hulluru Surya Prakash; Kamalraj, Mani

    2014-09-01

    We have synthesized and characterized a variety of fat-soluble, low-melting and medicinally useful 4-aryl-4H-chromenes from H-cardanol (side-chain perhydrogenated cardanol, 3-pentadecylphenol), a renewable and low-cost product from locally grown cashew nut trees (Anacardium occidentale L.). We incorporated H-cardanol into the aromatic rings of either 4H-chromene or phenol, or both. Substitution of C4SMe in N-methyl-4-(methylthio)-3-nitro-4H-chromene-2-amines with H-cardanol was regio-specific at the C6 position. PMID:25918806

  15. The Aryl Hydrocarbon Receptor: Differential Contribution to T Helper 17 and T Cytotoxic 17 Cell Development

    Hayes, Mark D.; Ovcinnikovs, Vitalijs; Smith, Andrew G.; Kimber, Ian; Dearman, Rebecca J

    2014-01-01

    The aryl hydrocarbon receptor (AhR) has been shown to be required for optimal Thelper (Th) 17 cell activation. Th17 cells provide immunity against extracellular pathogens and are implicated in autoimmune diseases. Herein, the role of the AhR in cytokine production by Th17, and by the analogous population of T cytotoxic (Tc)17 cells, has been examined. Lymph node Tc (CD8+) and Th (CD4+) cells were isolated by negative selection from naive AhR+/− and AhR−/− mice and polarised to Tc1/Th1 or Tc17...

  16. Balanced Ambipolar Poly(diketopyrrolopyrrole-alt-tetrafluorobenzene) Semiconducting Polymers Synthesized via Direct Arylation Polymerization.

    Wang, Kai; Wang, Guojie; Wang, Mingfeng

    2015-12-01

    The synthesis of an ambipolar π-conjugated copolymer consisting of alternating diketopyrrolopyrrole and tetrafluorobenzene via direct arylation polymerization (DAP) is reported. Two different combinations of monomers are investigated under various catalytic conditions for DAP. The target polymer obtained under an optimized catalytic condition shows minimal structural defects, a number-average molecular weight of 33.2 kDa, and balanced electron and hole mobility of 1 × 10(-2) cm(2) V(-1) S(-1) in the organic field-effect transistors fabricated and tested under ambient conditions. PMID:26421942

  17. Practical Ni-Catalyzed Aryl-Alkyl Cross-Coupling of Secondary Redox-Active Esters.

    Cornella, Josep; Edwards, Jacob T; Qin, Tian; Kawamura, Shuhei; Wang, Jie; Pan, Chung-Mao; Gianatassio, Ryan; Schmidt, Michael; Eastgate, Martin D; Baran, Phil S

    2016-02-24

    A new transformation is presented that enables chemists to couple simple alkyl carboxylic acids with aryl zinc reagents under Ni-catalysis. The success of this reaction hinges on the unique use of redox-active esters that allow one to employ such derivatives as alkyl halides surrogates. The chemistry exhibits broad substrate scope and features a high degree of practicality. The simple procedure and extremely inexpensive nature of both the substrates and pre-catalyst (NiCl2·6H2O, ca. $9.5/mol) bode well for the immediate widespread adoption of this method. PMID:26835704

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

    Yoshiaki Amakura; Morio Yoshimura; Masashi Takaoka; Haruka Toda; Tomoaki Tsutsumi; Rieko Matsuda; Reiko Teshima; Masafumi Nakamura; Hiroshi Handa; Takashi Yoshida

    2014-01-01

    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 chemi...

  19. In vitro evaluation of A-56619 (difloxacin) and A-56620: new aryl-fluoroquinolones.

    Stamm, J M; Hanson, C W; Chu, D T; Bailer, R; Vojtko, C; Fernandes, P B

    1986-01-01

    The in vitro antibacterial potencies of A-56619 and A-56620, two new aryl-fluoroquinolones, were compared with the potency of norfloxacin against a broad spectrum of organisms. Cefotaxime, aztreonam, piperacillin, imipenem, penicillin, and gentamicin were also tested for reference purposes. The MICs required to inhibit at least 90% of the strains tested ranged from 0.25 to 4 micrograms/ml for A-56619 and from 0.06 to 0.5 microgram/ml for A-56620 for members of the Enterobacteriaceae. A-56619 ...

  20. Hetero-Diels-Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles.

    Mlostoń, Grzegorz; Grzelak, Paulina; Mikina, Maciej; Linden, Anthony; Heimgartner, Heinz

    2015-01-01

    Selected hetaryl and aryl thioketones react with acetylenecarboxylates under thermal conditions in the presence of LiClO4 or, alternatively, under high-pressure conditions (5 kbar) at room temperature yielding thiopyran derivatives. The hetero-Diels-Alder reaction occurs in a chemo- and regioselective manner. The initially formed [4 + 2] cycloadducts rearrange via a 1,3-hydrogen shift sequence to give the final products. The latter were smoothly oxidized by treatment with mCPBA to the corresponding sulfones. PMID:26124858