Asymmetric synthesis and biological evaluation of N-cyclohexyl-4-[1-(2,4-dichlorophenyl)-1-(p-tolyl)methyl]piperazine-1-carboxamide as hCB1 receptor antagonists |
| |
Authors: | Gao Linghuan Li Min Meng Tao Peng Hongli Xie Xin Zhang Yongliang Jin Yu Wang Xin Zou Libo Shen Jingkang |
| |
Affiliation: | aState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China;bDepartment of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shengyang 110016, PR China |
| |
Abstract: | We recently discovered and reported a novel series of benzhydrylpiperazine derivatives bearing an asymmetric carbon atom that are potent and selective hCB1 inverse agonists. In the present study, we used Davis-Ellmann-type sulfonamide chemistry to asymmetrically synthesize two enantiomers of the most potent racemic N-cyclohexyl-4-[1-(2,4-dichlorophenyl)-1-(p-tolyl)methyl]piperazine-1-carbo-xamide [14]. Enantiomer separation and configuration assignment were carried out. Our results indicate that the R-configuration is the more active enantiomer, displaying enhanced antagonistic activity for hCB1 receptor, better oral bioavailability, and greater efficacy in the reduction of body weight in diet-induced obese mice. |
| |
Keywords: | Anti-obesity CB1 receptor Antagonist Asymmetric synthesis Enantiomer |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|