Title of article :
2,5-Diaminopyrimidines and 3,5-disubstituted azapurines as inhibitors of glycogen synthase kinase-3 (GSK-3)
Author/Authors :
Christopher Lum، نويسنده , , Jeff Kahl، نويسنده , , Linda Kessler، نويسنده , , Jeff Kucharski، نويسنده , , Jan Lundstr?m، نويسنده , , Stephen Miller، نويسنده , , Hiroshi Nakanishi، نويسنده , , Yazhong Pei، نويسنده , , Kent Pryor، نويسنده , , Edward Roberts.، نويسنده , , Lubomir Sebo، نويسنده , , Robert Sullivan، نويسنده , , Jan Urban، نويسنده , , Zhijun Wang، نويسنده ,
Abstract :
The discovery of two classes of pyrimidine-based inhibitors of GSK-3 is described. Optimization of these series led to inhibitors with IC50 < 10 nM and >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.
Keywords :
Diabetes , depression , Kinase inhibitors , GSK-3 , Aurora A , Molecular modeling , Alzheimer’s , bipolar disorder
