1396310-72-7Relevant academic research and scientific papers
Highly potent and selective 3-N-methylquinazoline-4(3H)-one based inhibitors of B-RafV600E kinase
Wenglowsky, Steve,Ren, Li,Grina, Jonas,Hansen, Joshua D.,Laird, Ellen R.,Moreno, David,Dinkel, Victoria,Gloor, Susan L.,Hastings, Gregg,Rana, Sumeet,Rasor, Kevin,Sturgis, Hillary L.,Voegtli, Walter C.,Vigers, Guy,Willis, Brandon,Mathieu, Simon,Rudolph, Joachim
, p. 1923 - 1927 (2014)
Herein we describe the design of a novel series of ATP competitive B-Raf inhibitors via structure-based methods. These 3-N-methylquinazoline-4(3H)-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 16, a potent, selective and orally available agent with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies. Our work also demonstrates that by replacing an aryl amide with an aryl sulfonamide, a multikinase inhibitor such as AZ-628, can be converted to a selective B-Raf inhibitor, a finding that should have broad application in kinase drug discovery.
HETEROCYCLIC SULFONAMIDES AS RAF INHIBITORS
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Page/Page column 90, (2012/09/21)
Compounds of Formula (I) are useful for inhibition of Raf kinases. Methods of using compounds of Formula (I), stereoisomers, tautomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
