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

  • Eur J Med Chem. 2009 Nov;44(11):4648-53. doi: 10.1016/j.ejmech.2009.06.037.
Peng Zhan  1 ,  Xinyong Liu ,  Zengjun Fang ,  Zhenyu Li ,  Christophe Pannecouque ,  Erik De Clercq
Affiliations
  • 1. Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China. [email protected]
PMID: 19628308 DOI: 10.1016/j.ejmech.2009.06.037
Abstract

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, 7 g and 7c were the most potent inhibitors of HIV-1 replication of the series (EC(50)=0.17+/-0.02, 0.36+/-0.19 and 0.39+/-0.05 microM, 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 (EC(50)=0.208 microM) and DLV (EC(50)=0.320 microM). The preliminary structure-activity relationships among the newly synthesized congeners are discussed briefly and rationalized by docking studies.