标题：Arylazolyl(azinyl)thioacetanilides. Part 10: Design, synthesis and biological evaluation of novel substituted imidazopyridinylthioacetanilides as potent HIV-1 inhibitors
作者机构：[Li, X] Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250 更多
通讯作者地址：[Zhan, P]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Chem Biol, 44 W Culture Rd, Jinan 250012, Shandong, Peoples R China.
来源：Bioorganic and medicinal chemistry
关键词：Anti-HIV-1 activity;Heterocycle;HIV;Imidazopyridine;NNRTIs;SAR;Scaffold hopping;Synthesis
摘要：In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with novel structures, we have employed a scaffold hopping strategy to explore the chemically diversed space of bioactive compounds. The original arylazolylthioacetanilide platform was replaced with different imidazopyridinyl- thioacetanilide scaffolds to yield the optimal pharmacophore moieties in order to generate novel NNRTIs with desirable potency. Some of the new compounds proved able to inhibit HIV-1 replication in the low micromolar range. In particular, compound 5b16 displayed the most potent anti-HIV-1 activity (EC 50 = 0.21 ± 0.06 μM), inhibiting HIV-1 IIIB replication in MT-4 cells more effectively than dideoxycytidine (EC 50 = 1.4 ± 0.1 μM) and similarly with nevirapine (EC 50 = 0.20 ± 0.10 μM). Preliminary structure-activity relationship (SAR) of the newly synthesized congeners is discussed, and molecular modeling study is performed to rationalize the SAR conclusions.