Potent N-(1, 3-thiazol-2-yl) pyridin-2-amine vascular endothelial growth factor receptor tyrosine kinase inhibitors with excellent pharmacokinetics and low affinity for …

…, C Buser-Doepner, KE Coll, C Fernandes…

Index: Bilodeau, Mark T.; Balitza, Adrienne E.; Koester, Timothy J.; Manley, Peter J.; Rodman, Leonard D.; Buser-Doepner, Carolyn; Coll, Kathleen E.; Fernandes, Christine; Gibbs, Jackson B.; Heimbrook, David C.; Huckle, William R.; Kohl, Nancy; Lynch, Joseph J.; Mao, Xianzhi; McFall, Rosemary C.; McLoughlin, Debra; Miller-Stein, Cynthia M.; Rickert, Keith W.; Sepp-Lorenzino, Laura; Shipman, Jennifer M.; Subramanian, Raju; Thomas, Kenneth A.; Wong, Bradley K.; Yu, Sean; Hartman, George D. Journal of Medicinal Chemistry, 2004 , vol. 47, # 25 p. 6363 - 6372

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Citation Number: 48

Abstract

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 ...