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

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• 作者：Idrees Mohammed ; Indrasena Reddy Kummetha ; Gatikrushna Singh ; Natalia Sharova ; Gianluigi Lichinchi ; Jason Dang ; Mario Stevenson ; Tariq M. Rana
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：August 25, 2016
• 年：2016
• 卷：59
• 期：16
• 页码：7677-7682
• 全文大小：316K
• 年卷期：0
• ISSN：1520-4804

文摘

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).