title: 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 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).
authors: Program for RNA Biology, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California 92037, United States.
authors: Idrees
authors: I
authors: Mohammed
authors: Department of Pediatrics, University of California San Diego School of Medicine , 9500 Gilman Drive, MC 0762, La Jolla, California 92093 United States.
authors: Indrasena Reddy
authors: IR
authors: Kummetha
authors: Program for RNA Biology, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California 92037, United States.
authors: Gatikrushna
authors: G
authors: Singh
authors: Division of Infectious Diseases, Miller School of Medicine, University of Miami , Miami, Florida 33136, United States.
authors: Natalia
authors: N
authors: Sharova
authors: Program for RNA Biology, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California 92037, United States.|Department of Pediatrics, University of California San Diego School of Medicine , 9500 Gilman Drive, MC 0762, La Jolla, California 92093 United States.
authors: Gianluigi
authors: G
authors: Lichinchi
authors: Department of Pediatrics, University of California San Diego School of Medicine , 9500 Gilman Drive, MC 0762, La Jolla, California 92093 United States.
authors: Jason
authors: J
authors: Dang
authors: Division of Infectious Diseases, Miller School of Medicine, University of Miami , Miami, Florida 33136, United States.
authors: Mario
authors: M
authors: Stevenson
authors: Program for RNA Biology, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California 92037, United States.|Department of Pediatrics, University of California San Diego School of Medicine , 9500 Gilman Drive, MC 0762, La Jolla, California 92093 United States.
authors: Tariq M
authors: TM
authors: Rana
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D015497:HIV-1 / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors*
chemical_list: D019380:Anti-HIV Agents; D014230:Triazoles; D054320:vif Gene Products, Human Immunodeficiency Virus