Article

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

Array BioPharma, Inc., 3200 Walnut Street, Boulder, CO 80301, United States.
Bioorganic & medicinal chemistry letters (impact factor: 2.65). 04/2012; 22(10):3387-91. DOI:10.1016/j.bmcl.2012.04.015 pp.3387-91
Source: PubMed

ABSTRACT 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.

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Keywords

ATP competitive B-Raf inhibitors
 
compound 17
 
drug design
 
excellent cellular potency
 
inhibitors exhibit
 
novel series
 
Optimization
 
orally available agent
 
pyridopyrimidin-7-one
 
robust tumor growth inhibition
 
striking B-Raf selectivity
 

Li Ren