Document Detail


Design and synthesis of disubstituted (4-piperidinyl)-piperazine derivatives as potent acetyl-CoA carboxylase inhibitors.
MedLine Citation:
PMID:  20537533     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid synthesis, play important roles in modulating energy metabolism. The inhibition of ACC has demonstrated promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models. We describe herein the structure-based design and synthesis of a novel series of disubstituted (4-piperidinyl)-piperazine derivatives as ACC inhibitors. Our structure-based approach led to the discovery of the indole derivatives 13i and 13j, which exhibited potent in vitro ACC inhibitory activity.
Authors:
Tomomichi Chonan; Hiroaki Tanaka; Daisuke Yamamoto; Miyoko Yashiro; Takahiro Oi; Daisuke Wakasugi; Ayumi Ohoka-Sugita; Fusayo Io; Hiroko Koretsune; Akira Hiratate
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Publication Detail:
Type:  Journal Article     Date:  2010-05-04
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  20     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2011-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  3965-8     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Ltd. All rights reserved.
Affiliation:
Taisho Pharmaceutical Co., Ltd, Kita-ku, Saitama-shi, Saitama, Japan. tomomichi.chonan@po.rd.taisho.co.jp
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MeSH Terms
Descriptor/Qualifier:
Acetyl-CoA Carboxylase / antagonists & inhibitors*
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Design*
Enzyme Inhibitors / chemical synthesis,  chemistry,  pharmacology*
Models, Molecular
Molecular Structure
Piperazines / chemical synthesis,  chemistry,  pharmacology*
Piperidines / chemical synthesis,  chemistry,  pharmacology*
Stereoisomerism
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Piperazines; 0/Piperidines; EC 6.4.1.2/Acetyl-CoA Carboxylase

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