Discovery of Aryl Aminoquinazoline Pyridones as Potent, Selective, and Orally Efficacious Inhibitors of Receptor Tyrosine Kinase c-Kit
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- 作者：Essa Hu ; Andrew Tasker ; Ryan D. White ; Roxanne K. Kunz ; Jason Human ; Ning Chen ; Roland Bü ; rli ; Randall Hungate ; Perry Novak ; Andrea Itano ; Xuxia Zhang ; Violeta Yu ; Yen Nguyen ; Yanyan Tudor ; Matthe
- 刊名：Journal of Medicinal Chemistry
- 出版年：2008
- 出版时间：June 12, 2008
- 年：2008
- 卷：51
- 期：11
- 页码：3065 - 3068
- 全文大小：332K
- 年卷期：v.51,no.11(June 12, 2008)
- ISSN：1520-4804
文摘
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.