2,5-Diaminopyrimidines and 3,5-disubstituted azapurines as inhibitors of glycogen synthase kinase-3 (GSK-3).

Abstract The discovery of two classes of pyrimidine-based inhibitors of GSK-3 is described. Optimization of these series led to inhibitors with IC 50 100-fold selectivity over Aurora A kinase. A proposed binding mode of 21b is presented. One compound ( 33 ) of the pyrimidine series showed promising pharmacokinetic parameters.