标题：Synthesis and biological evaluation of novel 5-alkyl-2-arylthio-6-((3,4-dihydroquinolin-1(2H)-yl)methyl)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
作者：Zhang J;Zhan P;Wu J;Li Z;Jiang Y;Ge W;Pannecouque C;De Clercq E;Liu X
作者机构：[Zhang, J] Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong 250012, Ch 更多
通讯作者地址：[Liu, XY]Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, 44 W Culture Rd, Jinan 250012, Shandong, Peoples R China.
来源：Bioorganic and medicinal chemistry
关键词：HIV-1; AIDS; NNRTIs; S-DABOs; Anti-HIV-1 activity
摘要：A series of novel S-DABO analogues of 5-alkyl-2-arylthio-6-((3,4-dihydroquinolin-1(2H)-yl)methyl)pyrimidin-4(3H)-ones were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Among them, the most potent HIV-1 inhibitors were compounds 6c1,6c6, and 6b1 (EC(50)=0.24 +/- 0.05, 0.38 +/- 0.13, 0.39 +/- 0.05 muM, respectively), which possess improved or similar HIV-1 inhibitory activity compared with nevirapine (NVP) (EC(50)=0.21 muM) and delavirdine (DLV) (EC(50)=0.32 muM). None of these compounds were active against HIV-2 replication. Furthermore, enzyme inhibitory assays were performed with selected derivatives against HIV-1 wtRT, confirming that the main target of these compounds is the HIV-1 RT and these new S-DABOs are acting as NNRTIs. The preliminary structure-activity relationship (SAR) of these new congeners is discussed briefly and rationalized by docking studies.