标题：Design, synthesis and biological evaluation of 3-benzyloxy-linked pyrimidinylphenylamine derivatives as potent HIV-1 NNRTIs
作者机构：[Rai, D] Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China;[ Chen, 更多
通讯作者地址：[Liu, XY]Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, 44 Wenhuaxi Rd, Jinan 250012, Peoples R China.
来源：Bioorganic and medicinal chemistry
关键词：Anti-HIV activity;HIV-1;NNRTIs;Pyrimidine;Reverse transcriptase
摘要：A novel series of 3-benzyloxy-linked pyrimidinylphenylamine derivatives (8a-8s) was designed, synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cell cultures. Most of the compounds inhibited wild-type (wt) HIV-1 replication in the lower micromolar concentration range (EC50 = 0.05-35 μM) with high selectivity index (SI) values (ranged from 10 to >4870). In particular, 8h and 8g displayed excellent antiretroviral activity against wt HIV-1 with low cytotoxicity (EC50 = 0.07 μM, CC 50 >347 μM, SI >4870; EC50 = 0.05 μM, CC 50 = 42 μM, SI = 777, respectively), comparable to that of the marked drug nevirapine (EC50 = 0.113 μM, CC50 >15 μM, SI >133). In order to confirm the binding target, 8h was selected to perform the anti-HIV-1 RT assay. Additionally, preliminary structure activity relationship (SAR) analysis and molecular docking studies of newly synthesized compounds were also discussed, as well as the predicted physicochemical properties.