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

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 mu M) by isosteric heterocycles resulted in the diScovery of a 1,2,3-trizole, 1d (IC50 = 1.2 mu M). We identified several potent HIV-1 inhibitors from a 1d based library including 5ax (IC50 = 0.01 mu M), 5bx (0.2 mu M), 2ey (0.4 mu M), 5ey (0.6 mu M), and 6bx (0.2 mu M).