Department of Medicinal Chemistry, Neuroscience Centre of Excellence of Drug Discovery, GlaxoSmithKline, Via A Fleming 4, 37135 Verona, Italy.
Bioorg Med Chem Lett. 2011 Aug 15;21(16):4823-7. doi: 10.1016/j.bmcl.2011.06.050. Epub 2011 Jun 29.
The discovery of a novel series of 2-(4-pyridyl)thienopyridinone GSK-3β inhibitors is reported. X-ray crystallography reveals its binding mode and enables rationalization of the SAR. The initial optimization of the template for improved cellular activity and predicted CNS penetration is also presented.
报道了一种新型的 2-(4-吡啶基)噻吩并[2,3-d]嘧啶酮 GSK-3β 抑制剂系列的发现。X 射线晶体学揭示了其结合模式，并能够对 SAR 进行合理化。还介绍了为提高细胞活性和预测 CNS 穿透性而对模板的初步优化。
