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 (EC(50) = 0.059 +/- 0.02 mu M, CC(50) > 283.25 mu M, SI > 4883). The structure-activity relationship (SAR) of these novel structural congeners is discussed. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.