Discovery of GSK1997132B a novel centrally penetrant benzimidazole PPARγ partial agonist

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5568-72. doi: 10.1016/j.bmcl.2011.06.088. Epub 2011 Jun 29.

Abstract

The peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor, thought to play a role in energy metabolism, glucose homeostasis and microglia-mediated neuroinflammation. A novel benzimidazole series of centrally penetrant PPARγ partial agonists has been identified. The optimization of PPARγ activity and in vivo pharmacokinetics leading to the identification of GSK1997132B a potent, metabolically stable and centrally penetrant PPARγ partial agonist, is described.

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Molecular Structure
  • PPAR gamma / antagonists & inhibitors*
  • PPAR gamma / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Benzimidazoles
  • GSK 1997132B
  • PPAR gamma
  • benzimidazole