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

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

  • J Med Chem. 2016 Aug 25;59(16):7677-82. doi: 10.1021/acs.jmedchem.6b00247.
Idrees Mohammed 1,  Indrasena Reddy Kummetha 2,  Gatikrushna Singh 1,  Natalia Sharova 3,  Gianluigi Lichinchi 1 2,  Jason Dang 2,  Mario Stevenson 3,  Tariq M Rana 1 2
Affiliations

Affiliations

  • 1 Program for RNA Biology, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California 92037, United States.
  • 2 Department of Pediatrics, University of California San Diego School of Medicine , 9500 Gilman Drive, MC 0762, La Jolla, California 92093 United States.
  • 3 Division of Infectious Diseases, Miller School of Medicine, University of Miami , Miami, Florida 33136, United States.
PMID: 27509004 DOI: 10.1021/acs.jmedchem.6b00247
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).

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