title: Novel 1,2,3-thiadiazole derivatives as HIV-1 NNRTIs with improved potency: Synthesis and preliminary SAR studies.
abstract: A novel synthetic route and anti-HIV activity evaluation of a new series of 2-(4-(2,4-dibromophenyl)-1,2,3-thiadiazol-5-ylthio)acetamide (TTA) derivatives are described. Bioactivity assay indicated that most of the title compounds showed good activities against HIV-1. In particular, compound 7c displayed the most potent anti-HIV-1 activity (EC(50)=36.4nM), inhibiting HIV-1 replication in MT-4 cells more effectively than NVP (by sevenfold) and DLV (by eightfold). The preliminary structure-activity relationships (SAR) of the newly synthesized congeners are discussed, and molecular modeling of compound 7c in complex with HIV-1 RT is described, allowing rationalization of some SAR conclusions.
authors.affiliation: Institute of Medicinal Chemistry, Shandong University, Jinan, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Fang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Defeng
authors.initials: D
authors.lastname: Wang
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Erik De
authors.initials: ED
authors.lastname: Clercq
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D003198:Computer Simulation; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000081:Acetamides; D019380:Anti-HIV Agents; C544482:N-(2-chloropyridin-3-yl)-2-(4-(2,4-dibromophenyl)-1,2,3-thiadiazol-5-ylthio)acetamide; D018894:Reverse Transcriptase Inhibitors; D013830:Thiadiazoles; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase