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.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cells, Cultured
  • Combinatorial Chemistry Techniques
  • Humans
  • Mice
  • Radioligand Assay
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology
  • Transcription Factors / agonists*
  • Transcriptional Activation

Substances

  • GW 501516
  • GW0742
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Transcription Factors