Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ) -: Synthesis and biological activity

We report the synthesis and biological activity of a new series of small molecule agonists of the human Peroxisome Proliferator-Activated Receptor delta (PPARdelta). Several hits were identified from our original libraries containing lipophilic carboxylic acids. Optimization of these hits by structure-guided design led to 7k (GW501516) and 71 (GW0742), which shows an EC50 Of 1.1 nM against PPARdelta with 1000-fold selectivity over the other human subtypes. (C) 2003 Elsevier Science Ltd. All rights reserved.