标题:Synthesis and Biological Evaluation of 6-Substituted 5-Alkyl-2-(phenylaminocarbonylmethylthio)pyrimidin-4(3H)- ones as Potent HIV-1 NNRTIs
作者:Mingyan Yu;Zhenyu Li;Shuai Liu
作者机构:[Yu, M] Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No.44 Wenhuaxi Road, Jinan 250012, China;[ Li, Z] In 更多
通讯作者:Yu, MY
通讯作者地址:[Yu, MY]Shandong Univ, Sch Pharmaceut Sci, Inst Med Chem, 44 Wenhuaxi Rd, Jinan 250012, Peoples R China.
来源:ChemMedChem
出版年:2011
卷:6
期:5
页码:826-833
DOI:10.1002/cmdc.201000555
关键词:antiviral agents;DABOs;HIV-1;medicinal chemistry;NNRTIs
摘要:A series of new 5-alkyl-2-phenylaminocarbonylmethylthiopyri-midin-4(3H)-ones bearing variously substituted arylmethyl moieties at the C6 position of the pyrimidine ring were synthesized and evaluated for anti-HIV activity in MT-4 cells. Most of these new congeners exhibited moderate to good activities against the wild-type virus, with EC_(50) values in the range of 1.40-0.19 μm. Among them, 2-[(4-cyanophenylamino)carbonyl-methylthio]-6-(2-chloro-6-fluorobenzyl)-5-ethylpyrimidin-4(3H)-one 4b6 is one of the compounds endowed with the highest broad-spectrum HIV-1 inhibitory activity, with EC_(50) values of 0.19 ± 0.005 μM against the wild-type virus, 1.05 ±0.24 μM (twofold resistance) against the E138K strain, and 2.38 ± 0.13 um (4.5-fold resistance) against the Y181C strain. Furthermore, reverse transcriptase (RT) inhibition assays against wild-type HIV-1 RT were performed with selected derivatives, confirming that the main target of these compounds is HIV-1 RT and that these new S-DABO analogues act as non-nucleoside RT inhibitors (NNRTIs). Structure-activity relationship and molecular modeling analyses of these new congeners are also discussed.
收录类别:SCOPUS;SCIE
WOS核心被引频次:12
Scopus被引频次:13
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-79954987862&doi=10.1002%2fcmdc.201000555&partnerID=40&md5=b91957d2acca7e950ecb42753b6d2631
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