3-Aryl-4-(arylhydrazono)-1H-pyrazol-5-ones: Highly ligand efficient and potent inhibitors of GSK3beta.

A series of 3-aryl-4-(arylhydrazono)-1H-pyrazol-5-one inhibitors of GSK3beta was developed from a low molecular weight, highly ligand efficient screening hit 1. Hit-to-lead optimization led to a number of highly potent inhibitors, while maintaining the high ligand efficiency of the screening hit.