- Phenoxyacetic acids as PPARδ partial agonists: synthesis, optimization, and in vivo efficacy.
Phenoxyacetic acids as PPARδ partial agonists: synthesis, optimization, and in vivo efficacy.
Bioorganic & medicinal chemistry letters (2011-03-19)
Karen A Evans, Barry G Shearer, David D Wisnoski, Dongchuan Shi, Steven M Sparks, Daniel D Sternbach, Deborah A Winegar, Andrew N Billin, Christy Britt, James M Way, Andrea H Epperly, Lisa M Leesnitzer, Raymond V Merrihew, Robert X Xu, Millard H Lambert, Jian Jin
PMID21414782
RÉSUMÉ
A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.