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The discovery of potent and selective pyridopyrimidin-7-one based inhibitors of B-RafV600E kinase

, : The discovery of potent and selective pyridopyrimidin-7-one based inhibitors of B-RafV600E kinase. Bioorganic & Medicinal Chemistry Letters 22(10): 3387-3391

Herein we describe the discovery of a novel series of ATP competitive B-Raf inhibitors via structure based drug design (SBDD). These pyridopyrimidin-7-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 17, a potent, selective and orally available agent with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies.


PMID: 22534450

DOI: 10.1016/j.bmcl.2012.04.015

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