Abstract
We report the synthesis and biological evaluation of aminopyridines substituted with benzoxazole. The SAR of the aminopyridines was explored to improve the inhibitory activity against c-Met and to decrease hERG affinity. These studies led to the discovery of amide 24 which showed good c-Met inhibitory potency, low affinity to hERG and favorable pharmacokinetic properties in rats.
2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Aminopyridines / administration & dosage
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Aminopyridines / chemistry
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Aminopyridines / pharmacokinetics
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Aminopyridines / pharmacology*
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Animals
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Benzoxazoles / chemistry*
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Drug Discovery
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Models, Molecular
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Rats
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Aminopyridines
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Benzoxazoles
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Protein Kinase Inhibitors
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RON protein
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Receptor Protein-Tyrosine Kinases