title: Discovery of novel 2-(3-(2-chlorophenyl)pyrazin-2-ylthio)-N-arylacetamides as potent HIV-1 inhibitors using a structure-based bioisosterism approach.
abstract: The present work is an extension of our ongoing efforts towards the development and identification of new molecules with anti-HIV activity which have previously led to the discovery of arylazolylthioacetanilides as highly active NNRTIs. In this article, a series of 2-2-(3-(2-chlorophenyl)pyrazin-2-ylthio)-N-arylacetamide derivatives were synthesized and evaluated for in vitro anti-HIV activity. Most of the tested compounds exhibited moderate activities against wild-type HIV-1. Among them, compound 6k showed significant activity against wild-type HIV-1 with an EC(50) value of 1.7μM, along with moderate activity against wild-type reverse transcriptase (RT). The preliminary structure-activity relationship (SAR) and docking calculations of this new series of compounds were also investigated, which may help designing more potent molecules.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Wenmin
authors.initials: W
authors.lastname: Chen
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Xuwang
authors.initials: X
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Erik De
authors.initials: ED
authors.lastname: Clercq
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013853:Thioacetamide / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D013853:Thioacetamide; D054303:HIV Reverse Transcriptase