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Pyridine-2-propanoic acids: Discovery of dual PPARalpha/gamma agonists as antidiabetic agents. 2006
Paul S Humphries, and
Jonathon V Almaden, and
Sandra J Barnum, and
Thomas J Carlson, and
Quyen-Quyen T Do, and
James D Fraser, and
Mary Hess, and
Young H Kim, and
Kathleen M Ogilvie, and
Shaoxian Sun
Department of Diabetes Chemistry, Pfizer Global R&D, 10770 Science Center Drive, San Diego, CA 92121, USA. paul.humphries@pfizer.com <paul.humphries@pfizer.com>
A series of novel pyridine-2-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compound (S)-13 was selected for further profiling.
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