北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 北京大学人类疾病基因研究中心  > 期刊论文
学科主题: 基础医学
题名:
Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists
作者: 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
发表日期: 2013-09-01
DOI: 10.1002/cjoc.201300363
卷: 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
所属项目编号: 30472093 ; 30872292 ; 90813025 ; 2009ZX09103-024 ; 201201020
项目资助者: 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
WOS记录号: WOS:000327882900005
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65489
Appears in Collections:基础医学院_北京大学人类疾病基因研究中心_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
Design and Synthesis of Tri-substituted Chiral Pyrrolidin-2-one Derivatives as CCR4 Antagonists.pdf(3585KB)期刊论文出版稿限制开放 联系获取全文

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

Recommended Citation:
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.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Sun, Wei]'s Articles
[Tian, Linjie]'s Articles
[Qi, Hui]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Sun, Wei]‘s Articles
[Tian, Linjie]‘s Articles
[Qi, Hui]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace