标题:Design, synthesis and biological evaluation of 3-benzyloxy-linked pyrimidinylphenylamine derivatives as potent HIV-1 NNRTIs
作者:Rai,D.;Chen,W.;Tian,Y.;Chen,X.;Zhan,P.;DeClercq,E.;Pannecouque,C.;Balzarini,J.;Liu,X.
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:Liu, XY
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
出版年:2013
卷:21
期:23
页码:7398-7405
DOI:10.1016/j.bmc.2013.09.051
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.
收录类别:SCOPUS;SCIE
WOS核心被引频次:1
Scopus被引频次:2
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84886946879&doi=10.1016%2fj.bmc.2013.09.051&partnerID=40&md5=8abfc5276cefdc0a178185e87b96fc82
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