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.
Mairi Sime  1 ,  Amanda C Allan ,  Paul Chapman ,  Charlotte Fieldhouse ,  Gerard M P Giblin ,  Mark P Healy ,  Millard H Lambert ,  Lisa M Leesnitzer ,  Ann Lewis ,  Raymond V Merrihew ,  Richard A Rutter ,  Rosemary Sasse ,  Barry G Shearer ,  Timothy M Willson ,  Robert X Xu ,  David J Virley
Affiliations
  • 1. Neurosciences Centre for Excellence in Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, CM19 5AW, United Kingdom. [email protected]
PMID: 21798739 DOI: 10.1016/j.bmcl.2011.06.088
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.

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