Abstract
A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC50 values of 8.6-81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC50s ranging from 0.57-16 μM.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminopyridines / chemical synthesis
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Aminopyridines / chemistry
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Drug Design
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Humans
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Molecular Structure
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Piperidines / chemical synthesis
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Piperidines / pharmacology*
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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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Proto-Oncogene Proteins c-met / chemistry
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Pyridones / chemical synthesis
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Pyridones / chemistry
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Structure-Activity Relationship
Substances
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Aminopyridines
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N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide
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Piperidines
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Protein Kinase Inhibitors
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Pyridones
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Proto-Oncogene Proteins c-met