Abstract
A potent series of inhibitors against the B-Raf(V600E) kinase have been developed that show excellent activity in cellular assays and good oral bioavailability in rats. The key structural features of the series are an arylsulfonamide headgroup, a thiazole core, and a fluorine ortho to the sulfonamide nitrogen.
Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Amino Acid Substitution
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Animals
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Binding Sites
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Catalytic Domain
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Fluorine / chemistry
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Microsomes, Liver / metabolism
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacokinetics
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
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Proto-Oncogene Proteins B-raf / genetics
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Proto-Oncogene Proteins B-raf / metabolism
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Rats
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Structure-Activity Relationship
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Sulfonamides / chemistry*
Substances
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Protein Kinase Inhibitors
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Sulfonamides
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Fluorine
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Proto-Oncogene Proteins B-raf