Referenced in: none

Automatically associated channels: Kv11.1

Title: 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 the hERG ion channel.

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

Journal, date & volume: J. Med. Chem., 2004 Dec 2 , 47, 6363-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15566305

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 kinase selectivity profile that can be accentuated with appropriate substitution.