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

…, E Chao, D Goreham, ML Sierra, C LeGrumelec…

Index: Sznaidman, Marcos L.; Haffner, Curt D.; Maloney, Patrick R.; Fivush, Adam; Chao, Esther; Goreham, Donna; Sierra, Michael L.; LeGrumelec, Christelle; Xu, H. Eric; Montana, Valerie G.; Lambert, Millard H.; Willson, Timothy M.; Oliver Jr., William R.; Sternbach, Daniel D. Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 9 p. 1517 - 1521

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Citation Number: 304

Abstract

We report the synthesis and biological activity of a new series of small molecule agonists of the human Peroxisome Proliferator-Activated Receptor δ (PPARδ). 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 7l (GW0742), which shows an EC50 of 1.1 nM against PPARδ with 1000-fold selectivity over the other human ...