4-Acylamino-6-arylfuro[2,3-d]pyrimidines: potent and selective glycogen synthase kinase-3 inhibitors.

Abstract Modeling studies of a furo[2,3- d ]pyrimidine GSK-3 hit compound 1 superimposed onto the X-ray crystal structure of a legacy pyrazolo[3,4- c ]pyridazine GSK-3 inhibitor 2 led to the identification of 4-acylamino-6-arylfuro[2,3- d ]pyrimidine template 3 . Synthesis of analogues based on template 3 has resulted in a number of potent and selective GSK-3β inhibitors. The most potent and selective compound was the m -pyridyl analogue 24 .