Abstract
Novel 2-benzylidene-benzofuran-3-ones were designed and synthesized to mimic flavopiridol, a well-established inhibitor of cyclin-dependent kinases (CDKs) which is currently undergoing clinical evaluation. The underlying design concepts as well as the synthesis and structure-activity relationships (CDKs 1, 2, and 4 enzyme assays) of these mimics are described. Inhibitors of CDKs 1 and 2 that are more potent and selective than flavopiridol were obtained.
MeSH terms
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Benzylidene Compounds / chemical synthesis*
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Benzylidene Compounds / chemistry
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CDC2 Protein Kinase / antagonists & inhibitors
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CDC2 Protein Kinase / chemistry
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CDC2-CDC28 Kinases*
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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Cyclin-Dependent Kinases / chemistry
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Flavonoids / chemistry*
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Furans / chemical synthesis*
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Furans / chemistry
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Models, Molecular
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Molecular Mimicry
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Piperidines / chemistry*
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / chemistry
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Proto-Oncogene Proteins*
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Structure-Activity Relationship
Substances
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Benzylidene Compounds
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Enzyme Inhibitors
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Flavonoids
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Furans
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Piperidines
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Proto-Oncogene Proteins
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alvocidib
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Protein Serine-Threonine Kinases
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CDC2 Protein Kinase
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CDC2-CDC28 Kinases
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases