Document Detail


Novel 2,3-dihydrobenzofuran-2-carboxylic acids: highly potent and subtype-selective PPARalpha agonists with potent hypolipidemic activity.
MedLine Citation:
PMID:  16107159     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The design and synthesis of a novel class of 2,3-dihydrobenzofuran-2-carboxylic acids as highly potent and subtype-selective PPARalpha agonists are reported. Systematic study of structure-activity relationships has identified several key structural elements within this class for maintaining the potency and subtype selectivity. Select compounds were evaluated in animal models of dyslipidemia using Syrian hamsters and male Beagle dogs, and all these compounds displayed excellent cholesterol- and triglyceride-lowering activity at dose levels that were much lower than the marketed weak PPARalpha agonist fenofibrate.
Authors:
Guo Q Shi; James F Dropinski; Yong Zhang; Conrad Santini; Soumya P Sahoo; Joel P Berger; Karen L Macnaul; Gaochao Zhou; Arun Agrawal; Raul Alvaro; Tian-Quan Cai; Melba Hernandez; Samuel D Wright; David E Moller; James V Heck; Peter T Meinke
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  48     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-18     Completed Date:  2005-10-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5589-99     Citation Subset:  IM    
Affiliation:
Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900, USA. guoqiang_shi@merck.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antilipemic Agents / chemical synthesis*,  chemistry,  pharmacology
Benzofurans / chemical synthesis*,  chemistry,  pharmacology
Carboxylic Acids / chemical synthesis*,  chemistry,  pharmacology
Cholesterol / blood
Cricetinae
Dogs
Humans
Hyperlipidemias / drug therapy
Male
Mesocricetus
Molecular Conformation
PPAR alpha / agonists*,  genetics
Radioligand Assay
Stereoisomerism
Structure-Activity Relationship
Transcriptional Activation
Triglycerides / blood
Chemical
Reg. No./Substance:
0/2-ethyl-5-(3-(2-chloro-4-(trifluoromethoxy)phenoxy)propoxy)-2,3-dihydro-1-benzofuran-2-carboxylic acid; 0/Antilipemic Agents; 0/Benzofurans; 0/Carboxylic Acids; 0/PPAR alpha; 0/Triglycerides; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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