1,2,3-triazoles as amide bioisosteres: Discovery of a new class of potent HIV-1 Vif antagonists

Idrees Mohammed, Indrasena Reddy Kummetha, Gatikrushna Singh, Natalia Sharova, Gianluigi Lichinchi, Jason Dang, Mario Stevenson, Tariq M. Rana

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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, Id (IC50 = 1.2 μM). We identified several potent HIV-1 inhibitors from a Id based library including 5ax (IC50 = 0.01 μM), 5bx (0.2 μM), 2ey (0.4 μM), 5ey (0.6 μM), and 6bx (0.2 μ M).

Original languageEnglish (US)
Pages (from-to)7677-7682
Number of pages6
JournalJournal of medicinal chemistry
Volume59
Issue number16
DOIs
StatePublished - Aug 25 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

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