Neurosciences Centre for Excellence in Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, CM19 5AW, United Kingdom.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5568-72. doi: 10.1016/j.bmcl.2011.06.088. Epub 2011 Jun 29.
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.
过氧化物酶体增殖物激活受体 γ（PPARγ）是一种配体激活的核受体，被认为在能量代谢、葡萄糖稳态和小胶质细胞介导的神经炎症中发挥作用。已经鉴定出一系列新型苯并咪唑类中枢穿透性 PPARγ 部分激动剂。本文描述了对 PPARγ 活性和体内药代动力学的优化，从而鉴定出一种有效的、代谢稳定且中枢穿透性的 PPARγ 部分激动剂 GSK1997132B。
