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 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).
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology*
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Dose-Response Relationship, Drug
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Drug Discovery*
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HIV-1 / drug effects*
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Microbial Sensitivity Tests
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Molecular Structure
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Structure-Activity Relationship
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Triazoles / chemical synthesis
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Triazoles / chemistry
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Triazoles / pharmacology*
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vif Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors*
Substances
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Anti-HIV Agents
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Triazoles
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vif Gene Products, Human Immunodeficiency Virus