Novel 1,2,3-thiadiazole derivatives as HIV-1 NNRTIs with improved potency: Synthesis and preliminary SAR studies

作者：Zhan, Peng; Liu, Xinyong^*; Li, Zhenyu; Fang, Zengjun; Li, Zhong; Wang, Defeng; Pannecouque, Christophe; De Clercq, Erik

来源：Bioorganic & Medicinal Chemistry, 2009, 17(16): 5920-5927.

DOI：10.1016/j.bmc.2009.07.004

• HIV-1
• AIDS
• NNRTIs
• Thiadiazole thioacetanilides
• Heterocycle
• Antiviral activity

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 (EC50 = 36.4 nM), 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.

• 出版日期2009-8-15
• 单位山东大学; 河北医科大学