1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1 Vif Antagonists
Idrees MohammedProgram
for RNA Biology, Sanford Burnham Prebys Medical Discovery Institute, La
Jolla, California 92037, United StatesIndrasena Reddy KummethaDepartment
of Pediatrics, University of California San Diego School of Medicine, 9500 Gilman Drive, MC 0762, La Jolla, California 92093 United StatesGatikrushna SinghDiscovery InstituteН. П. ШароваDivision
of Infectious Diseases, Miller School of Medicine, University of Miami, Miami, Florida 33136, United StatesGianluigi LichinchiUniversity of California San DiegoJason DangDepartment
of Pediatrics, University of California San Diego School of Medicine, 9500 Gilman Drive, MC 0762, La Jolla, California 92093 United StatesMario StevensonDivision
of Infectious Diseases, Miller School of Medicine, University of Miami, Miami, Florida 33136, United StatesTariq M. RanaUniversity of California San Diego
2016en
ABI
Annotatsiya
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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