Arylazolyl(azinyl)thioacetanilides. Part 20: Discovery of novel purinylthioacetanilides derivatives as potent HIV-1 NNRTIs via a structure-based bioisosterism approach

作者：Lu, Xueyi; Li, Xiao; Yang, Jiapei; Huang, Boshi; Kang, Dongwei; Zhao, Fabao; Zhou, Zhongxia; De Clercq, Erik; Daelemans, Dirk; Pannecouque, Christophe^*; Zhan, Peng^*; Liu, Xinyong^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(18): 4424-4433.

DOI：10.1016/j.bmc.2016.07.041

• HIV-1
• AIDS
• NNRTIs
• Purinylthioacetanilide
• Anti-HIV activity
• Drug design
• Bioisosterism

By means of structure-based bioisosterism approach, a series of novel purinylthioacetanilide derivatives were designed, synthesized and evaluated as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Some of the tested compounds were found to be active against wild-type (WT) HIV-1 (IIIB) with EC50 in the range of 0.78-4.46 mu M. Among them, LAD-8 displayed the most potent anti-HIV activity (EC50 = 0.78 mu M, SI = 24). In addition, LBD-6 showed moderate activity against L100I mutant (EC50 = 5.64 mu M) and double mutant strain RES056 (EC50 = 22.24 mu M). Preliminary structure-activity relationships (SARs) were discussed in detail. Molecular modeling study was used to predict the optimal conformation in the NNRTI binding site, which may play a guiding role in further rational optimization.

• 出版日期2016-9-15
• 单位河北医科大学; 山东大学