title: 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.
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.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China. zhanpeng1982@163.com
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Fang
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D019380:Anti-HIV Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase