Abstract
A series of amidoheteroaryl compounds were designed and synthesized as inhibitors of B-Raf kinase. Several compounds from the series show excellent potency in biochemical, phenotypic and mode of action cellular assays. Potent examples from the series have also demonstrated good plasma exposure following an oral dose in rodents and activity against the Ras-Raf pathway in tumor bearing mice.
MeSH terms
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Administration, Oral
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Animals
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Mice
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Models, Chemical
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Mutation*
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
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Rats
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Structure-Activity Relationship
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raf Kinases / metabolism
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ras Proteins / metabolism
Substances
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Enzyme Inhibitors
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Proto-Oncogene Proteins B-raf
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raf Kinases
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ras Proteins