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Non-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors

Journal Article · · Bioorg. Med. Chem. Lett.

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.

Research Organization:
Argonne National Laboratory (ANL)
Sponsoring Organization:
USDOE
OSTI ID:
1006183
Journal Information:
Bioorg. Med. Chem. Lett., Journal Name: Bioorg. Med. Chem. Lett. Journal Issue: (23) ; 12, 2009 Vol. 19; ISSN 0960-894X
Country of Publication:
United States
Language:
ENGLISH

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