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1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1 Vif Antagonists.

ABSTRACT: RN-18 based viral infectivity factor (Vif), Vif antagonists reduce viral infectivity by rescuing APOBEC3G (A3G) expression and enhancing A3G-dependent Vif degradation. Replacement of amide functionality in RN-18 (IC50 = 6 ?M) by isosteric heterocycles resulted in the discovery of a 1,2,3-trizole, 1d (IC50 = 1.2 ?M). We identified several potent HIV-1 inhibitors from a 1d based library including 5ax (IC50 = 0.01 ?M), 5bx (0.2 ?M), 2ey (0.4 ?M), 5ey (0.6 ?M), and 6bx (0.2 ?M).

SUBMITTER: Mohammed I

PROVIDER: S-EPMC5534211 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1 Vif Antagonists.

Mohammed Idrees I Kummetha Indrasena Reddy IR Singh Gatikrushna G Sharova Natalia N Lichinchi Gianluigi G Dang Jason J Stevenson Mario M Rana Tariq M TM

Journal of medicinal chemistry 20160810 16

RN-18 based viral infectivity factor (Vif), Vif antagonists reduce viral infectivity by rescuing APOBEC3G (A3G) expression and enhancing A3G-dependent Vif degradation. Replacement of amide functionality in RN-18 (IC50 = 6 μM) by isosteric heterocycles resulted in the discovery of a 1,2,3-trizole, 1d (IC50 = 1.2 μM). We identified several potent HIV-1 inhibitors from a 1d based library including 5ax (IC50 = 0.01 μM), 5bx (0.2 μM), 2ey (0.4 μM), 5ey (0.6 μM), and 6bx (0.2 μM). ...[more]

PMID: 27509004

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