文献类型：期刊文献

英文题名：Discovery of a Novel CCR5 Antagonist Lead Compound Through Fragment Assembly

作者：Liu, Yanqing[2];Zhou, Enkun[1,3];Yu, Kunqian[4];Zhu, Jin[2];Zhang, Yu[2];Xie, Xin[1];Li, Jian[2];Jiang, Hualiang[2,4]

机构：[1]Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[3]Southwest Univ, Sch Biotechnol, Chongqing 400715, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China

年份：2008

卷号：13

期号：10

起止页码：2426

外文期刊名：MOLECULES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000260505100007)】；

基金：We gratefully acknowledge the financial support from the 863 Hi-Tech Program of China (Grants 2006AA020404, 2006AA01A124), and the Shanghai Rising-Star Program (A type) of Shanghai Ministry of Science and Technology (Grant 07QA14013). We also thank Shanghai Supercomputing Center (http://www. ssc. net. cn/) for providing the computational resources.

语种：英文

外文关键词：CCR5 antagonist; fragment assembly; HIV-1; molecular modeling

摘要：CCR5, as the major co-receptor for HIV-1 entry, is an attractive novel target for the pharmaceutical industry in the HIV-1 therapeutic area. In this study, based on the structures of maraviroc and 1,4-bis(4-(7-chloroquinolin-4-yl) piperazin-1-yl) butane-1,4-dione (1), which was identified using structure-based virtual screening in conjunction with a calcium mobilization assay, a series of novel small molecule CCR5 antagonists have been designed and synthesized through fragment assembly. Preliminary SARs were obtained, which are in good agreement with the molecular binding model and should prove helpful for future antagonist design. The novel scaffold presented here might also be useful in the development of maraviroc-derived second generation CCR5 antagonists.