Abstract
A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.
MeSH terms
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Aminopyridines / chemical synthesis*
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Aminopyridines / chemistry
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Aminopyridines / pharmacology*
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Animals
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Humans
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Mice
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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 c-met / antagonists & inhibitors*
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Pyrroles / chemical synthesis*
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Pyrroles / chemistry
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Pyrroles / pharmacology*
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Stomach Neoplasms / chemically induced
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Stomach Neoplasms / pathology
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Structure-Activity Relationship
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Urea / analogs & derivatives
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Urea / chemical synthesis*
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Urea / pharmacology*
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Xenograft Model Antitumor Assays
Substances
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Aminopyridines
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Protein Kinase Inhibitors
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Pyrroles
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Urea
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Proto-Oncogene Proteins c-met