1. Discovery of GSK1997132B a novel centrally penetrant benzimidazole PPARγ partial agonist
- Author
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Mairi, Sime, 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, Timothy M, Wilson, Robert X, Xu, and David J, Virley
- Subjects
chemistry.chemical_classification ,Benzimidazole ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Drug discovery ,Organic Chemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Peroxisome proliferator-activated receptor ,Stereoisomerism ,Pharmacology ,Biochemistry ,Partial agonist ,PPAR gamma ,Structure-Activity Relationship ,chemistry.chemical_compound ,Nuclear receptor ,Drug Discovery ,Molecular Medicine ,Glucose homeostasis ,Benzimidazoles ,Penetrant (biochemical) ,Receptor ,Molecular Biology - 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.
- Published
- 2011