标题:Discovery of 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular hybridization based on crystallographic overlays
作者:Chen,W.;Zhan,P.;Rai,D.;DeClercq,E.;Pannecouque,C.;Balzarini,J.;Zhou,Z.;Liu,H.;Liu,X.
作者机构:[Chen, W] Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44, West Culture Road, 250012 Jinan, Shandong 更多
通讯作者:Liu, XY
通讯作者地址:[Liu, XY]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China.
来源:Bioorganic and medicinal chemistry
出版年:2014
卷:22
期:6
页码:1863-1872
DOI:10.1016/j.bmc.2014.01.054
关键词:2-Pyridone;Docking;Drug design;HIV;Molecular hybridization;NNRTIs
摘要:Based on crystallographic overlays of the known inhibitors TMC125 and R221239 complexed in RT, we designed a novel series of 4-phenoxy-6-(phenylamino) pyridin-2(1H)-one derivatives as HIV NNRTIs by molecular hybridization approach. The biological testing results indicated that 2-pyridone scaffold of these inhibitors was indispensable for their anti-HIV-1 activity, and substitution of halogen at the 3-position of the 2-pyridone ring would decrease the anti-HIV activity. Four most potent compounds had anti-HIV-1 IIIB activities at low micromolar concentrations (EC50 = 0.15-0.84 μM), comparable to that of nevirapine and delavidine. Some compounds were selected to test their anti-HIV-1 RT inhibitory action and to perform molecular modeling studies to predict the binding mode of these 2-pyridone derivatives.
收录类别:SCOPUS;SCIE
WOS核心被引频次:16
Scopus被引频次:16
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84896697008&doi=10.1016%2fj.bmc.2014.01.054&partnerID=40&md5=73fcded86e774acbd8083025c27329ad
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