| Structure-based design of indole propionic acids as novel PPARalpha/gamma co-agonists. | |
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MedLine Citation:
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PMID: 16737814 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the quest for novel PPARalpha/gamma co-agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia, we have used a structure-based design approach to identify propionic acids with a 1,5-disubstituted indole scaffold as potent PPARalpha/gamma activators. Compounds 13, 24, and 28 are examples of submicromolar dual agonists with different alpha/gamma EC50 ratios that are selective against the delta-isoform. Analysis of the X-ray complex structure of PPARgamma with the indole propionic acid 13 provides a rationalization for some of the observed SAR. |
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Authors:
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Bernd Kuhn; Hans Hilpert; Jörg Benz; Alfred Binggeli; Uwe Grether; Roland Humm; Hans Peter Märki; Markus Meyer; Peter Mohr |
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Publication Detail:
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Type: Journal Article Date: 2006-06-05 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 16 ISSN: 0960-894X ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-06-20 Completed Date: 2006-09-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 4016-20 Citation Subset: IM |
Affiliation:
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F. Hoffmann-La Roche Ltd, Discovery Research Basel, CH-4070 Basel, Switzerland. bernd.kuhn@roche.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Drug Design Indoles / chemistry*, pharmacology* Molecular Structure PPAR alpha / agonists* PPAR gamma / agonists* Structure-Activity Relationship X-Ray Diffraction |
| Chemical | |
Reg. No./Substance:
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0/Indoles; 0/PPAR alpha; 0/PPAR gamma; 830-96-6/indolepropionic acid |
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