1. Design and Biological Evaluation of Novel, Balanced Dual PPARα/γ Agonists
- Author
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Uwe Grether, Armin Ruf, Daniel Schlatter, Markus Meyer, Kurt Püntener, Jörg Benz, Hans Hilpert, Peter Mohr, Hans Peter Märki, Bernd Kuhn, Alfred Binggeli, Agnès Bénardeau, Susanne Raab, and Denise Blum
- Subjects
Pharmacology ,Phenylpropionates ,Stereochemistry ,Chemistry ,Organic Chemistry ,nutritional and metabolic diseases ,Stereoisomerism ,Computational biology ,Crystallography, X-Ray ,Biochemistry ,Rats ,PPAR gamma ,Mice ,Structure-Activity Relationship ,Diabetes Mellitus, Type 2 ,Drug Design ,Drug Discovery ,Animals ,Humans ,Molecular Medicine ,Computer Simulation ,PPAR alpha ,General Pharmacology, Toxicology and Pharmaceutics ,Hypolipidemic Agents ,Biological evaluation - Abstract
An X-ray-guided design approach led to the identification of a novel, balanced class of alpha-ethoxy-phenylpropionic acid-derived dual PPARalpha/gamma agonists. The series shows a wide range of PPARalpha/gamma ratios within a rather narrow structural space. Advanced compounds possess favorable physicochemical and pharmacokinetic profiles and show a high efficacy in T2D and dyslipidemia animal models.
- Published
- 2009
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