1.
Bioorg Med Chem Lett
; 21(11): 3488-92, 2011 Jun 01.
Article
in English
| MEDLINE
| ID: mdl-21536432
ABSTRACT
The synthesis and biological evaluation of non-oxime pyrazole based B-Raf inhibitors is reported. Several oxime replacements have been prepared and have shown excellent enzyme activity. Further optimization of fused pyrazole 2a led to compound 38, a selective and potent B-Raf inhibitor.
Subject(s)
Enzyme Inhibitors/pharmacology , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Pyrazoles/chemical synthesis , Pyrazoles/pharmacology , Animals , Crystallography, X-Ray , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Inhibitory Concentration 50 , Mice , Molecular Structure , Oximes/chemistry , Pyrazoles/chemistry
2.
Bioorg Med Chem Lett
; 18(16): 4692-5, 2008 Aug 15.
Article
in English
| MEDLINE
| ID: mdl-18676143
ABSTRACT
Herein we describe a novel pyrazole-based class of ATP competitive B-Raf inhibitors. These inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. A subset of these inhibitors has demonstrated the ability to inhibit downstream ERK phosphorylation in LOX tumors from mouse xenograft studies.