Discovery of benzhydrylpiperazine derivatives as CB1 receptor inverse agonists via privileged structure-based approach

被引：11

作者：

Meng, Tao ^{[1
]}

Wang, Jue ^{[2
]}

Peng, Hongli ^{[1
]}

Fang, Guanghua ^{[1
]}

Li, Min ^{[1
]}

Xiong, Bing ^{[1
]}

Xie, Xin ^{[2
]}

Zhang, Yongliang ^{[1
]}

Wang, Xin ^{[1
]}

Shen, Jingkang ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

[2] Natl Ctr Drug Screening, Shanghai 201203, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 03期

基金：

中国国家自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

Benzhydrylpiperazine; Privileged structure; Cannabinoid receptor 1(CB1); Anti-obesity; MEDICINAL CHEMISTRY; ANTAGONISTS; RIMONABANT; DRUG; OBESITY; SYSTEM;

D O I：

10.1016/j.ejmech.2009.12.018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The present study describes the identification via privileged structure-based approach of the benzhydrylpiperazine moiety as a potential scaffold to develop novel CB1 receptor modulators. Efficient structural optimization of the initial four hit compounds led to a high quality lead series, represented by compound 6c. Compound 6c is a highly potent and selective CB1 receptor inverse agonist that is able to reduce body weight in diet-induced obese Sprague-Dawley rats. The preparation of privileged structure-based library, the progression from hit to lead, the structure-activity relationships in the lead series and in vitro and in vivo activity of compound 6c are discussed. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：1133 / 1139

页数：7

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