Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity

  • Bioorg Med Chem Lett. 2003 May 5;13(9):1517-21. doi: 10.1016/s0960-894x(03)00207-5.
Marcos L Sznaidman  1 ,  Curt D Haffner ,  Patrick R Maloney ,  Adam Fivush ,  Esther Chao ,  Donna Goreham ,  Michael L Sierra ,  Christelle LeGrumelec ,  H Eric Xu ,  Valerie G Montana ,  Millard H Lambert ,  Timothy M Willson ,  William R Oliver Jr ,  Daniel D Sternbach
Affiliations
  • 1. GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA.
PMID: 12699745 DOI: 10.1016/s0960-894x(03)00207-5
Abstract

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 7l (GW0742), which shows an EC(50) of 1.1 nM against PPARdelta with 1000-fold selectivity over the other human subtypes.

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