Document Detail


Asymmetric synthesis and biological evaluation of N-cyclohexyl-4-[1-(2,4-dichlorophenyl)-1-(p-tolyl)methyl]piperazine-1-carboxamide as hCB1 receptor antagonists.
MedLine Citation:
PMID:  21937154     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Linghuan Gao; Min Li; Tao Meng; Hongli Peng; Xin Xie; Yongliang Zhang; Yu Jin; Xin Wang; Libo Zou; Jingkang Shen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-1
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  -     ISSN:  1768-3254     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Affiliation:
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China; Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shengyang 110016, PR China.
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