Potent and selective pyrazolo[1,5-a]pyrimidine based inhibitors of B-Raf(V600E) kinase with favorable physicochemical and pharmacokinetic properties.
Bioorg Med Chem Lett, 2012/1/15;22(2):1165-8.
Ren L[1], Laird ER, Buckmelter AJ, Dinkel V, Gloor SL, Grina J, Newhouse B, Rasor K, Hastings G, Gradl SN, Rudolph J
Affiliations
PMID: 22196124DOI: 10.1016/j.bmcl.2011.11.092
Impact factor: 2.94
Abstract
Herein we describe a novel series of ATP competitive B-Raf inhibitors based on the pyrazolo[1,5-a]pyrimidine scaffold. These 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 improved physicochemical and pharmacokinetic properties.
MeSH terms
Animals; Chemistry, Physical; Crystallography, X-Ray; Dose-Response Relationship, Drug; Enzyme Inhibitors; Mice; Models, Molecular; Molecular Structure; Proto-Oncogene Proteins B-raf; Pyrazoles; Pyrimidines; Stereoisomerism; Structure-Activity Relationship
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