Substituted 3-Imidazo[l,2-alpha]pyridin-3-yl-4-(l,2,3,4-tetrahydro-[l,4]diazepino-[6,7,l-/i/]indol-7-yl)pyrrole-2,5-diones as Highly Selective and Potent Inhibitors of Glycogen Synthase Kinase-3

摘要

Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor.Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin,making GSK3 an attractive target for the treatment of type 2 diabetes.Herein we report the discovery of a series of potent and selective GSK3 inhibitors.Compounds 7-12 show oral activity in an in vivo model of type II diabetes,and 9 and 12 have desirable PK properties.