The Experts below are selected from a list of 4575 Experts worldwide ranked by ideXlab platform
Zhengqiang Wang - One of the best experts on this subject based on the ideXlab platform.
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5 Silylated 3 1 2 3 triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus
Journal of Medicinal Chemistry, 2015Co-Authors: Sanjeev Kumar V Vernekar, Li Qiu, Jing Zhang, Jayakanth Kankanala, Robert J Geraghty, Zhengqiang WangAbstract:West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5′-Silylated nucleoside scaffold derived from 3′-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure–activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5′-Silyl Group and the substituent of 3′-triazole or its bioisosteres. Particularly interesting is the 5′ Silyl Group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that...
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5 Silylated 3 1 2 3 triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus
Journal of Medicinal Chemistry, 2015Co-Authors: Sanjeev Kumar V Vernekar, Li Qiu, Jing Zhang, Jayakanth Kankanala, Robert J Geraghty, Zhengqiang WangAbstract:West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5'-Silylated nucleoside scaffold derived from 3'-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure-activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5'-Silyl Group and the substituent of 3'-triazole or its bioisosteres. Particularly interesting is the 5' Silyl Group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that these compounds likely confer antiviral activity via binding to methyltransferase (MTase).
Sanjeev Kumar V Vernekar - One of the best experts on this subject based on the ideXlab platform.
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5 Silylated 3 1 2 3 triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus
Journal of Medicinal Chemistry, 2015Co-Authors: Sanjeev Kumar V Vernekar, Li Qiu, Jing Zhang, Jayakanth Kankanala, Robert J Geraghty, Zhengqiang WangAbstract:West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5′-Silylated nucleoside scaffold derived from 3′-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure–activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5′-Silyl Group and the substituent of 3′-triazole or its bioisosteres. Particularly interesting is the 5′ Silyl Group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that...
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5 Silylated 3 1 2 3 triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus
Journal of Medicinal Chemistry, 2015Co-Authors: Sanjeev Kumar V Vernekar, Li Qiu, Jing Zhang, Jayakanth Kankanala, Robert J Geraghty, Zhengqiang WangAbstract:West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5'-Silylated nucleoside scaffold derived from 3'-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure-activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5'-Silyl Group and the substituent of 3'-triazole or its bioisosteres. Particularly interesting is the 5' Silyl Group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that these compounds likely confer antiviral activity via binding to methyltransferase (MTase).
Gilles Pierre - One of the best experts on this subject based on the ideXlab platform.
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SmI2 induced cross coupling of nitrones and Silyl acrylates : synthesis of polyhydroxylated pyrrolidines
2011Co-Authors: Gilles PierreAbstract:Les nitrones peuvent être réduites par le diiodure de samarium et réagir selon une additionconjuguée avec des acrylates-Silylés, Silylés ou ,diSilylés. Ce couplage réducteur,développé avec des aldonitrones simples, a conduit à des dérivés Silylés de g-Nhydroxyaminoacides.Ces derniers ont pu être réduits puis cyclisés en g-lactames substituéspar un Groupement Silylé, dont la position et la configuration dépendent de l’acrylate dedépart. L’oxydation de Tamao-Fleming a ensuite permis la conversion des composés Silylésen leurs correspondants hydroxylés avec rétention de configuration. Cet enchaînementréactionnel a alors été appliquée à une nitrone cyclique polyalkoxylée dérivée du L-xylose, cequi a permis les synthèses de la 7-desoxy Uniflorine A et de la (+)-Australine, deuxpyrrolizidines polyhydroxylées inhibiteurs de glucosidases.Nitrones are reduced by samarium diiodide and react through a conjugated addition with Silylacrylates. This cross coupling, developed with simple aldonitrones, allowed the preparation ofSilyl g-N-hydroxyaminoacids derivatives. The latter were reduced and cyclised in g-lactams inwhich the position and the configuration of the Silyl Group depend of the starting acrylate.Tamao-Fleming oxidation was used for the conversion of Silyl Group to hydroxyl Group withretention of configuration. Then, the reaction was applied to a cyclic polyalkoxy nitronederived from L-xylose and it allowed the synthesis of 7-deoxy Uniflorine A and (+)-Australine, polyhydroxylated pyrrolizidines exhibiting glucosidases inhibition
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Couplage croisé induit par SmI2 de nitrones avec des acrylates Silylés : synthèse de Pyrrolizidines polyhydroxylées
HAL CCSD, 2011Co-Authors: Gilles PierreAbstract:Nitrones are reduced by samarium diiodide and react through a conjugated addition with Silylacrylates. This cross coupling, developed with simple aldonitrones, allowed the preparation ofSilyl g-N-hydroxyaminoacids derivatives. The latter were reduced and cyclised in g-lactams inwhich the position and the configuration of the Silyl Group depend of the starting acrylate.Tamao-Fleming oxidation was used for the conversion of Silyl Group to hydroxyl Group withretention of configuration. Then, the reaction was applied to a cyclic polyalkoxy nitronederived from L-xylose and it allowed the synthesis of 7-deoxy Uniflorine A and (+)-Australine, polyhydroxylated pyrrolizidines exhibiting glucosidases inhibition.Les nitrones peuvent être réduites par le diiodure de samarium et réagir selon une additionconjuguée avec des acrylates-Silylés, Silylés ou ,diSilylés. Ce couplage réducteur,développé avec des aldonitrones simples, a conduit à des dérivés Silylés de g-Nhydroxyaminoacides.Ces derniers ont pu être réduits puis cyclisés en g-lactames substituéspar un Groupement Silylé, dont la position et la configuration dépendent de l’acrylate dedépart. L’oxydation de Tamao-Fleming a ensuite permis la conversion des composés Silylésen leurs correspondants hydroxylés avec rétention de configuration. Cet enchaînementréactionnel a alors été appliquée à une nitrone cyclique polyalkoxylée dérivée du L-xylose, cequi a permis les synthèses de la 7-desoxy Uniflorine A et de la (+)-Australine, deuxpyrrolizidines polyhydroxylées inhibiteurs de glucosidases
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Couplage croisé induit par SmI2 de nitrones avec des acrylates Silylés. Synthèse de Pyrrolizidines polyhydroxylées
2011Co-Authors: Gilles Pierre, Py SandrineAbstract:Les nitrones peuvent être réduites par le diiodure de samarium et réagir selon une additionconjuguée avec des acrylates-Silylés, Silylés ou ,diSilylés. Ce couplage réducteur,développé avec des aldonitrones simples, a conduit à des dérivés Silylés de g-Nhydroxyaminoacides.Ces derniers ont pu être réduits puis cyclisés en g-lactames substituéspar un Groupement Silylé, dont la position et la configuration dépendent de l acrylate dedépart. L oxydation de Tamao-Fleming a ensuite permis la conversion des composés Silylésen leurs correspondants hydroxylés avec rétention de configuration. Cet enchaînementréactionnel a alors été appliquée à une nitrone cyclique polyalkoxylée dérivée du L-xylose, cequi a permis les synthèses de la 7-desoxy Uniflorine A et de la (+)-Australine, deuxpyrrolizidines polyhydroxylées inhibiteurs de glucosidases.Nitrones are reduced by samarium diiodide and react through a conjugated addition with Silylacrylates. This cross coupling, developed with simple aldonitrones, allowed the preparation ofSilyl g-N-hydroxyaminoacids derivatives. The latter were reduced and cyclised in g-lactams inwhich the position and the configuration of the Silyl Group depend of the starting acrylate.Tamao-Fleming oxidation was used for the conversion of Silyl Group to hydroxyl Group withretention of configuration. Then, the reaction was applied to a cyclic polyalkoxy nitronederived from L-xylose and it allowed the synthesis of 7-deoxy Uniflorine A and (+)-Australine, polyhydroxylated pyrrolizidines exhibiting glucosidases inhibition.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF
Jayakanth Kankanala - One of the best experts on this subject based on the ideXlab platform.
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5 Silylated 3 1 2 3 triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus
Journal of Medicinal Chemistry, 2015Co-Authors: Sanjeev Kumar V Vernekar, Li Qiu, Jing Zhang, Jayakanth Kankanala, Robert J Geraghty, Zhengqiang WangAbstract:West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5′-Silylated nucleoside scaffold derived from 3′-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure–activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5′-Silyl Group and the substituent of 3′-triazole or its bioisosteres. Particularly interesting is the 5′ Silyl Group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that...
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5 Silylated 3 1 2 3 triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus
Journal of Medicinal Chemistry, 2015Co-Authors: Sanjeev Kumar V Vernekar, Li Qiu, Jing Zhang, Jayakanth Kankanala, Robert J Geraghty, Zhengqiang WangAbstract:West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5'-Silylated nucleoside scaffold derived from 3'-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure-activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5'-Silyl Group and the substituent of 3'-triazole or its bioisosteres. Particularly interesting is the 5' Silyl Group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that these compounds likely confer antiviral activity via binding to methyltransferase (MTase).
Li Qiu - One of the best experts on this subject based on the ideXlab platform.
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5 Silylated 3 1 2 3 triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus
Journal of Medicinal Chemistry, 2015Co-Authors: Sanjeev Kumar V Vernekar, Li Qiu, Jing Zhang, Jayakanth Kankanala, Robert J Geraghty, Zhengqiang WangAbstract:West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5′-Silylated nucleoside scaffold derived from 3′-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure–activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5′-Silyl Group and the substituent of 3′-triazole or its bioisosteres. Particularly interesting is the 5′ Silyl Group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that...
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5 Silylated 3 1 2 3 triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus
Journal of Medicinal Chemistry, 2015Co-Authors: Sanjeev Kumar V Vernekar, Li Qiu, Jing Zhang, Jayakanth Kankanala, Robert J Geraghty, Zhengqiang WangAbstract:West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5'-Silylated nucleoside scaffold derived from 3'-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure-activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5'-Silyl Group and the substituent of 3'-triazole or its bioisosteres. Particularly interesting is the 5' Silyl Group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that these compounds likely confer antiviral activity via binding to methyltransferase (MTase).