| (2R)-2-ethylchromane-2-carboxylic acids: discovery of novel PPARalpha/gamma dual agonists as antihyperglycemic and hypolipidemic agents. | |
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MedLine Citation:
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PMID: 15163205 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A series of chromane-2-carboxylic acid derivatives was synthesized and evaluated for PPAR agonist activities. A structure-activity relationship was developed toward PPARalpha/gamma dual agonism. As a result, (2R)-7-(3-[2-chloro-4-(4-fluorophenoxy)phenoxy]propoxy)-2-ethylchromane-2-carboxylic acid (48) was identified as a potent, structurally novel, selective PPARalpha/gamma dual agonist. Compound 48 exhibited substantial antihyperglycemic and hypolipidemic activities when orally administered in three different animal models: the db/db mouse type 2 diabetes model, a Syrian hamster lipid model, and a dog lipid model. |
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Authors:
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Hiroo Koyama; Daniel J Miller; Julia K Boueres; Ranjit C Desai; A Brian Jones; Joel P Berger; Karen L MacNaul; Linda J Kelly; Thomas W Doebber; Margaret S Wu; Gaochao Zhou; Pei-ran Wang; Marc C Ippolito; Yu-Sheng Chao; Arun K Agrawal; Ronald Franklin; James V Heck; Samuel D Wright; David E Moller; Soumya P Sahoo |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 47 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2004 Jun |
Date Detail:
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Created Date: 2004-05-27 Completed Date: 2004-07-02 Revised Date: 2005-11-17 |
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: 3255-63 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. hiroo_koyama@merck.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antilipemic Agents / chemical synthesis*, chemistry, pharmacokinetics, pharmacology Benzopyrans / chemical synthesis*, chemistry, pharmacokinetics, pharmacology Chromans / chemical synthesis*, chemistry, pharmacokinetics, pharmacology Cricetinae Diabetes Mellitus, Type 2 / drug therapy, genetics Dogs Humans Hypoglycemic Agents / chemical synthesis*, chemistry, pharmacokinetics, pharmacology Macaca mulatta Male Mesocricetus Mice Phenyl Ethers / chemical synthesis*, chemistry, pharmacokinetics, pharmacology Rats Rats, Sprague-Dawley Receptors, Cytoplasmic and Nuclear / agonists*, genetics, metabolism Stereoisomerism Structure-Activity Relationship Trans-Activators / chemical synthesis, chemistry, pharmacology Transcription Factors / agonists*, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/7-(3-(2-chloro-4-(4-fluorophenoxy)phenoxy)propoxy)-2-ethylchromane-2-carboxylic acid; 0/Antilipemic Agents; 0/Benzopyrans; 0/Chromans; 0/Hypoglycemic Agents; 0/Phenyl Ethers; 0/Receptors, Cytoplasmic and Nuclear; 0/Trans-Activators; 0/Transcription Factors |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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