Synthesis and anti-HIV activity evaluation of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)-N-acetamides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)acetamide (TTA) derivatives were synthesized and evaluated as potent inhibitors of HIV-1. Among the newly disclosed TTAs, compounds 7f, 7g and 7c were the most potent inhibitors of HIV-1 replication of the series (EC50 = 0.17 +/- 0.02, 0.36 +/- 0.19 and 0.39 +/- 0.05 mu M, respectively), coupled with a reasonable selectivity index (SI > 1452, >845, and >774, respectively). They possess improved or similar HIV-1 inhibitory activity compared with NVP (EC50 = 0.208 mu M) and DLV (EC50 = 0.320 mu M). The preliminary structure-activity relationships among the newly synthesized congeners are discussed briefly and rationalized by docking studies. Crown Copyright (C) 2009 Published by Elsevier Masson SAS. All rights reserved.