Abstract
A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / pharmacology
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Coumarins / chemical synthesis*
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Coumarins / chemistry
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Coumarins / pharmacology*
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Drug Design*
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Humans
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Inhibitory Concentration 50
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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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Umbelliferones / chemical synthesis
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Umbelliferones / chemistry
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Umbelliferones / pharmacology
Substances
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Coumarins
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N-(1-((7,8-dihydroxy-2-oxo-2H-chromen-3-yl)amino)-1-oxoheptan-2-yl)-7,8-dihydroxy-2-oxo-2H-chromene-3-carboxamide
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N-(1-((7,8-dihydroxy-2-oxo-2H-chromen-3-yl)amino)-1-oxooctan-2-yl)-7,8-dihydroxy-2-oxo-2H-chromene-3-carboxamide
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Protein Kinase Inhibitors
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Umbelliferones
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Adenosine Triphosphate
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Proto-Oncogene Proteins c-met
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daphnetin