| Novel 2,3-dihydrobenzofuran-2-carboxylic acids: highly potent and subtype-selective PPARalpha agonists with potent hypolipidemic activity. | |
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MedLine Citation:
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PMID: 16107159 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 48 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-08-18 Completed Date: 2005-10-14 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 5589-99 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900, USA. guoqiang_shi@merck.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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