Synthesis of the PPARbeta/delta-selective agonist GW501516 and C4-thiazole-substituted analogs

Bioorg Med Chem Lett. 2006 Jan 1;16(1):49-54. doi: 10.1016/j.bmcl.2005.09.060. Epub 2005 Oct 18.

Abstract

Sequential, position-selective, Pd-catalyzed cross-coupling reactions of 2,4-dibromo-5-hydroxymethylthiazole provided the scaffold for the synthesis of GW501516, the most potent PPARbeta/delta agonist yet described, and equally selective analogs at the thiazole-C4 position.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Cell Line
  • Chemistry, Pharmaceutical
  • Drug Design
  • Genes, Reporter
  • Genetic Techniques
  • Globins / genetics
  • HeLa Cells
  • Humans
  • Hydroxybenzoates / chemistry*
  • Ligands
  • Lipids / chemistry
  • Models, Chemical
  • PPAR delta / agonists*
  • PPAR-beta / agonists*
  • Palladium / pharmacology
  • Promoter Regions, Genetic
  • Quinazolines / chemical synthesis*
  • Quinazolines / pharmacology
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology
  • Time Factors
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • CB676475
  • GW 501516
  • Hydroxybenzoates
  • Ligands
  • Lipids
  • PPAR delta
  • PPAR-beta
  • Quinazolines
  • Thiazoles
  • Palladium
  • Globins