1,2,3-Thiadiazole thioacetanilides as a novel class of potent HIV-1 non-nucleoside reverse transcriptase inhibitors

A novel series of 1,2,3-thiadiazole thioacetanilide (TTA) derivatives have been designed, synthesized and evaluated for its anti-HIV activities in MT-4 cells. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Among them, 2-[4-(2,4-dichlorophenyl)-1,2,3-thiadiazol-5-ylthio]-N-(2-nitrophenyl)acetamide 7d2 was identified as the most promising compound (EC50 = 0.059 ± 0.02 μM, CC50 > 283.25 μM, SI > 4883). The structure–activity relationship (SAR) of these novel structural congeners is discussed.

Graphical abstractA novel series of 1,2,3-thiadiazole thioacetanilide (TTA) derivatives have been designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. The structure–activity relationship (SAR) is discussed.Figure optionsDownload full-size imageDownload as PowerPoint slide