Structure-based design of indole propionic acids as novel PPARα/γ co-agonists

B Kuhn, H Hilpert, J Benz, A Binggeli, U Grether…

Index: Kuhn, Bernd; Hilpert, Hans; Benz, Joerg; Binggeli, Alfred; Grether, Uwe; Humm, Roland; Maerki, Hans Peter; Meyer, Markus; Mohr, Peter Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 15 p. 4016 - 4020

Full Text: HTML

Citation Number: 53

Abstract

In the quest for novel PPARα/γ 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 PPARα/γ activators. Compounds 13, 24, and 28 are examples of submicromolar dual agonists with different α/γ EC50 ratios that are selective against the δ-isoform. Analysis of the X-ray complex ...