学科主题基础医学
Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists
Sun, Wei1; Tian, Linjie3; Qi, Hui3; Jiang, Dan2; Wang, Ying3; Li, Song2; Xiao, Junhai2; Yang, Xiaohong1
关键词CCR4 antagonists tri-substituted chiral pyrrolidin-2-one derivatives synthesis
刊名CHINESE JOURNAL OF CHEMISTRY
2013-09-01
DOI10.1002/cjoc.201300363
31期:9页:1144-1152
收录类别SCI ; IC
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary
研究领域[WOS]Chemistry
关键词[WOS]CHEMOKINE-LIKE FACTOR-1 ; MOLECULAR-CLONING ; FUNCTIONAL LIGAND ; RECEPTOR 4 ; T-CELLS ; EXPRESSION ; TARC
英文摘要

A series of tri-substituted chiral pyrrolidin-2-one derivatives have been designed and synthesized as CC chemokine receptor 4 (CCR4) antagonists. The structure of CCR4 was built by homology modeling. Asymmetric synthesis was applied to synthesize the R,R configuration chiral pyrrolidin-2-one scaffold. The stereoisomeric configurations of the compounds were identified by 2D H-1-H-1 COSY spectroscopy and 1D NOESY spectroscopy. This method was more economical and convenient than traditional X-ray single crystal diffraction. In addition, the interactions between these compounds and the N-terminal extracellular tail of CCR4 were studied using capillary zone electrophoresis. The CCR4 chemotaxis inhibition effect was tested in CCR4-transfected HEK293 cells. Several compounds showed potent activities as CCR4 antagonists. Among these compounds, 1c is the most active one. Its apparent binding constant of CZE experiment result is (1.569 +/- 0.11)x10(5) Lmol(-1), and its percentage inhibition of the HEK293/CCR4 cells migration with the concentration of 1 mu molL-1 in DMSO is 59%. And compound 1f has slightly higher affinity to N-terminal of CCR4 according to its apparent binding constant than 1b because of the introduced ester linkage. Further studies on the mechanism of these compounds are in progress.

语种英语
WOS记录号WOS:000327882900005
项目编号30472093 ; 30872292 ; 90813025 ; 2009ZX09103-024 ; 201201020
资助机构National Natural Science Foundation of China ; National Major Science & ; Technology Specific Project ; Young Scientific Research Fund Project for Department of Science and Technology of Jilin Province
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65489
专题北京大学基础医学院_北京大学人类疾病基因研究中心
作者单位1.Jilin Univ, Sch Pharmaceut Sci, Changchun 130021, Jilin, Peoples R China
2.Beijing Inst Pharmacol & Toxicol, Lab Computer Aided Drug Design & Discovery, Beijing 100850, Peoples R China
3.Peking Univ, Ctr Human Dis Genom, Beijing 100083, Peoples R China
推荐引用方式
GB/T 7714
Sun, Wei,Tian, Linjie,Qi, Hui,et al. Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists[J]. CHINESE JOURNAL OF CHEMISTRY,2013,31(9):1144-1152.
APA Sun, Wei.,Tian, Linjie.,Qi, Hui.,Jiang, Dan.,Wang, Ying.,...&Yang, Xiaohong.(2013).Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists.CHINESE JOURNAL OF CHEMISTRY,31(9),1144-1152.
MLA Sun, Wei,et al."Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists".CHINESE JOURNAL OF CHEMISTRY 31.9(2013):1144-1152.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
Design and Synthesis(3585KB)期刊论文出版稿开放获取CC BY-NC-SA浏览 请求全文
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
[Sun, Wei]的文章
[Tian, Linjie]的文章
[Qi, Hui]的文章
百度学术
百度学术中相似的文章
[Sun, Wei]的文章
[Tian, Linjie]的文章
[Qi, Hui]的文章
必应学术
必应学术中相似的文章
[Sun, Wei]的文章
[Tian, Linjie]的文章
[Qi, Hui]的文章
相关权益政策
暂无数据
收藏/分享
文件名: Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists.pdf
格式: Adobe PDF
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。