Discovery of Aryl Aminoquinazoline Pyridones as Potent, Selective, and Orally Efficacious Inhibitors of Receptor Tyrosine Kinase c-Kit
Journal of Medicinal Chemistry2008Vol. 51(11), pp. 3065–3068
Citations Over TimeTop 18% of 2008 papers
Essa Hu, Andrew S. Tasker, Ryan D. White, Roxanne K. Kunz, Jason Human, Ning Chen, Roland W. Bürli, Randall W. Hungate, Perry M. Novak, Andrea Itano, Xuxia Zhang, Violeta Yu, Yen Nguyen, Yanyan Tudor, Matthew Plant, Shaun Flynn, Yang Xu, Kristin L. Meagher, Douglas A. Whittington, Gordon Ng
Abstract
Inhibition of c-Kit has the potential to treat mast cell associated fibrotic diseases. We report the discovery of several aminoquinazoline pyridones that are potent inhibitors of c-Kit with greater than 200-fold selectivity against KDR, p38, Lck, and Src. In vivo efficacy of pyridone 16 by dose-dependent inhibition of histamine release was demonstrated in a rodent pharmacodynamic model of mast cell activation.
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