标题：Discovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors by exploring the structure-activity relationship of solvent-exposed regions I
作者：Kang, Dongwei; Wang, Zhao; Chen, Meng; Feng, Da; Wu, Gaochan; Zhou, Zhongxia; Jing, Lanlan; Zuo, Xiaofang; Jiang, Xiangyi; Daelemans 更多 作者机构：[Kang, Dongwei; Wang, Zhao; Feng, Da; Wu, Gaochan; Zhou, Zhongxia; Jing, Lanlan; Zuo, Xiaofang; Jiang, Xiangyi; Zhan, Peng; Liu, Xinyong] Shandong Uni 更多
通讯作者：Zhan, P;Liu, XY
通讯作者地址：[Zhan, P; Liu, XY]Shandong Univ, Dept Med Chem, Key Lab Chem Biol, Minist Educ,Sch Pharmaceut Sci, Jinan, Shandong, Peoples R China.
来源：CHEMICAL BIOLOGY & DRUG DESIGN
关键词：DAPY; HIV-1; NNRTIs; solvent-exposed region I; thiophene[3;; 2-d]pyrimidine
摘要：Two novel series of human immunodeficiency virus-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) bearing a thiophene[3,2-d]pyrimidine scaffold and sulfonamide linker in the right wing have been identified, which demonstrated activity against the wild-type (WT) HIV-1 strain in MT-4 cells with inhibitory concentrations ranging from micromolar to submicromolar. Especially, against the mutant strains K103N and E138K, most compounds exhibited more potent activity than against WT HIV-1. Compound 7 (EC50 = 0.014, 0.031 mu M) achieved the most potent activity against the two mutants, being more effective than that of nevirapine (NVP, EC50 = 7.572, 0.190 mu M) and comparable to that of etravirine (ETV, EC50 = 0.004, 0.014 mu M). Molecular docking experiments on the novel analogs have also suggested that the extensive network of main chain hydrogen bonds are important in the binding mode, which may provide valuable insights for further optimization.