2. Academic Validation
  3. Discovery of aryl aminoquinazoline pyridones as potent, selective, and orally efficacious inhibitors of receptor tyrosine kinase c-Kit

Discovery of aryl aminoquinazoline pyridones as potent, selective, and orally efficacious inhibitors of receptor tyrosine kinase c-Kit

  • J Med Chem. 2008 Jun 12;51(11):3065-8. doi: 10.1021/jm800188g.
Essa Hu 1,  Andrew Tasker,  Ryan D White,  Roxanne K Kunz,  Jason Human,  Ning Chen,  Roland Bürli,  Randall Hungate,  Perry Novak,  Andrea Itano,  Xuxia Zhang,  Violeta Yu,  Yen Nguyen,  Yanyan Tudor,  Matthew Plant,  Shaun Flynn,  Yang Xu,  Kristin L Meagher,  Douglas A Whittington,  Gordon Y Ng
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Amgen Inc, Thousand Oaks, CA 91320-1799, USA. ehu@amgen.com
PMID: 18447379 DOI: 10.1021/jm800188g
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 VEGFR2/KDR/Flk-1, 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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