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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Ren L,Ahrendt KA,Grina J,Laird ER,Buckmelter AJ,Hansen JD,Newhouse B,Moreno D,Wenglowsky S,Dinkel V,Gloor SL,Hastings G,Rana S,Rasor K,Risom T,Sturgis HL,Voegtli WC,Mathieu S

doi

10.1016/j.bmcl.2012.04.015

subject

Has Abstract

pub_date

2012-05-15 00:00:00

pages

3387-91

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)00454-4

journal_volume

22

pub_type

杂志文章

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