Design, Synthesis and in Vitro Test of Novel Non-ATP Competitive Glycogen Synthase Kinase-3β(GSK-3β) Inhibitors

OBJECTIVE To discover novel non-ATP competitive glycogen synthase kinase-3β(GSK-3β) inhibitors. METHODS A virtual screening was conducted by Autodock program, which docked the small drug-like molecules of Maybridge library at the non-ATP binding site of GSK-3β. The target compounds had been designed based on the virtual screening result and successfully synthesized through Knoevenagel reaction, cyclization and N-alkylation. The inhibition to GSK-3β was tested by in vitro enzamic test. RESULTS 5-benzyl-2-(furan-2-yl)-2,3-dihydrobenzob1,4 thiazepin-4(5H)-one showed moderate inhibition to GSK-3β in vitro (IC50 47.69±2.38 μmol·L^-1). CONCLUSION The discovered new active compound is structurally different to other inhibitors of GSK-3β and worthy of further study as a novel lead compound.