Design and synthesis of 7-hydroxy-1H-benzoimidazole derivatives as novel inhibitors of glycogen synthase kinase-3β

A hydroxy functional group was introduced as the hydrogen bond donor and acceptor at the hinge region of protein kinase in order to develop novel ATP-competitive inhibitors. Several derivatives of 7-hydroxyl-1H-benzoimidazole were designed as inhibitors of glycogen synthase kinase-3β with the help of ab initio calculations and a docking study. Enzymatic assay and an X-ray complex study showed that these designed compounds were highly potent ATP-competitive inhibitors.