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A series of N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitors have been developed that possess optimal properties. Compounds have been discovered that exhibit excellent in vivo potency. The particular challenges of overcoming hERG binding activity and QTc increases in vivo in addition to achieving good pharmacokinetics have been acomplished by discovering a unique class of amine substituents. These compounds have a favorable kinase selectivity profile that can be accentuated with appropriate substitution.

Pyrimidine derivativesPyrimidine derivatives R 0510 2,4-Disubstituted Pyrimidines: A Novel Class of KDR Kinase Inhibitors. -In order to find novel small molecule inhibitors of the KDR kinase domain, various kinds of compounds such as (VI) are synthesized. Among them the derivative (VIb) is the most potent one with an IC50 of 6nM in the KDR kinase assay and an IC50 of 19nM in a cell-based assay. -(MANLEY*, P. J.; BALITZA, A. E.; BILODEAU, M. T.; COLL, K. E.; HARTMAN, G. D.; MCFALL, R. C.; RICKERT, K. W.; RODMAN, L. D.; THOMAS, K. A.; Bioorg. Med.

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