Abstract
Aryl phenyl ureas with a 4-quinazolinoxy substituent at the meta-position of the phenyl ring are potent inhibitors of mutant and wild type BRAF kinase. Compound 7 (1-(5-tert-butylisoxazol-3-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea hydrochloride) exhibits good pharmacokinetic properties in rat and mouse and is efficacious in a mouse tumor xenograft model following oral dosing.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Dose-Response Relationship, Drug
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Mice
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
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Proto-Oncogene Proteins B-raf / metabolism*
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Quinazolines / chemical synthesis
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Quinazolines / chemistry
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Quinazolines / pharmacology*
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Rats
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Stereoisomerism
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Structure-Activity Relationship
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Tissue Distribution
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Urea / analogs & derivatives
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Urea / chemistry
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Urea / pharmacology*
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Xenograft Model Antitumor Assays
Substances
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Protein Kinase Inhibitors
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Quinazolines
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Urea
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Proto-Oncogene Proteins B-raf