IR@PKUHSC  > 北京大学药学院  > 化学生物学系
学科主题药学
Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains
Li, Amin1; Ouyang, Yabo3; Wang, Ziyun2; Cao, Yuanyuan1; Liu, Xiangyi1; Ran, Li2; Li, Chao1; Li, Li1; Zhang, Liang1; Qiao, Kang2; Xu, Weisi3; Huang, Yang3; Zhang, Zhili1; Tian, Chao1; Liu, Zhenming2; Jiang, Shibo4,5,6; Shao, Yiming3; Du, Yansheng7; Ma, Liying3; Wang, Xiaowei1; Liu, Junyi1,2
刊名JOURNAL OF MEDICINAL CHEMISTRY
2013-05-09
DOI10.1021/jm400102x
56期:9页:3593-3608
收录类别SCI ; IC
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Medicinal
资助者National Natural Science Foundation of China ; Ministry of Science and Technology of China ; SKLID ; National Natural Science Foundation of China ; Ministry of Science and Technology of China ; SKLID
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]IMMUNODEFICIENCY-VIRUS TYPE-1 ; DRUG-RESISTANCE ; POSITIONAL ADAPTABILITY ; BIOLOGICAL EVALUATION ; ETRAVIRINE TMC125 ; WILD-TYPE ; DESIGN ; PREVENTION ; COMPLEXES ; SERIES
英文摘要

Novel 6-substituted-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated. Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs). The diastereoisomers of 26-trans and 26-cis were synthesized separately and confirmed with HPLC and NOESY spectra. The 26-trans isomers had an activity about 400-fold more potent than that of 26-cis. The pair of 26-trans enantiomers, one of the most potent inhibitors with EC50 of 4 nM and selectivity index (SI) of 75000, was highly effective against a panel of RTIs-resistant strains with single (Y181C and K103N) or double (A17) mutations in reverse transcriptase. The results suggest that these novel pyridinone derivatives have the potential to be further developed as new antiretroviral drugs with improved antiviral efficacy and drug resistance profile.

语种英语
所属项目编号21172014 ; 20972011 ; 21042009 ; 30872232 ; 812111023 ; 81172733 ; 2009ZX09301-010 ; 2011SICLID102
资助者National Natural Science Foundation of China ; Ministry of Science and Technology of China ; SKLID ; National Natural Science Foundation of China ; Ministry of Science and Technology of China ; SKLID
WOS记录号WOS:000318892500015
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65894
专题北京大学药学院_化学生物学系
作者单位1.Fudan Univ, Inst Med Microbiol, Shanghai 200032, Peoples R China
2.Peking Univ, Dept Biol Chem, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
4.Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent NCAIDS, State Key Lab Infect Dis Prevent & Control, Beijing 102206, Peoples R China
5.Fudan Univ, Lab Med Mol Virol, Shanghai Med Coll, Minist Educ, Shanghai 200032, Peoples R China
6.Fudan Univ, Lab Med Mol Virol, Shanghai Med Coll, Minist Hlth, Shanghai 200032, Peoples R China
7.Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA
推荐引用方式
GB/T 7714
Li, Amin,Ouyang, Yabo,Wang, Ziyun,et al. Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56(9):3593-3608.
APA Li, Amin.,Ouyang, Yabo.,Wang, Ziyun.,Cao, Yuanyuan.,Liu, Xiangyi.,...&Liu, Junyi.(2013).Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains.JOURNAL OF MEDICINAL CHEMISTRY,56(9),3593-3608.
MLA Li, Amin,et al."Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains".JOURNAL OF MEDICINAL CHEMISTRY 56.9(2013):3593-3608.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Li, Amin]的文章
[Ouyang, Yabo]的文章
[Wang, Ziyun]的文章
百度学术
百度学术中相似的文章
[Li, Amin]的文章
[Ouyang, Yabo]的文章
[Wang, Ziyun]的文章
必应学术
必应学术中相似的文章
[Li, Amin]的文章
[Ouyang, Yabo]的文章
[Wang, Ziyun]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。