Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 47, Issue 25, Pages 6363-6372Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm049697f
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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.
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