- Non-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors.
Non-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors.
Bioorganic & medicinal chemistry letters (2009-10-30)
Dan M Berger, Nancy Torres, Minu Dutia, Dennis Powell, Greg Ciszewski, Ariamala Gopalsamy, Jeremy I Levin, Kyung-Hee Kim, Weixin Xu, James Wilhelm, YongBo Hu, Karen Collins, Larry Feldberg, Steven Kim, Eileen Frommer, Donald Wojciechowicz, Robert Mallon
PMID19864136
摘要
As part of our research effort to discover B-Raf kinase inhibitors, we prepared a series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamides. X-ray crystallography studies revealed that one of the more potent inhibitors (10n) bound to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.
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