Article ID Journal Published Year Pages File Type
1376990 Bioorganic & Medicinal Chemistry Letters 2006 5 Pages PDF
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 structure of PPARγ with the indole propionic acid 13 provides a rationalization for some of the observed SAR.

Graphical abstractThe structure-based discovery, chemical synthesis, X-ray structure, and biological in vitro data of indole propionic acids as potent PPARα/γ co-agonists are described.Figure optionsDownload full-size imageDownload as PowerPoint slide

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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