Identification of 2-(4-pyridyl)thienopyridinones as GSK-3β inhibitors

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.

Graphical abstractThis manuscript is related to the identification of a novel series of GSK-3 inhibitors by a computational analysis based on docking experiments and synthesis of a structure based array on of 2-(4-pyridyl)thienopyridinone core. This approach allowed a timely and efficient way to identify initial starting points for future lead optimization efforts.Figure optionsDownload full-size imageDownload as PowerPoint slide