Abstract
Inhibitors of histone deacetylases (HDACs) have been shown to induce differentiation and/or apoptosis of human tumor cells. Novel 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides have been prepared as a new class of HDAC inhibitors and evaluated for their antiproliferative activity and HDAC inhibitory activity. Incorporation of a 1,4-phenylene carboxamide linker, shown by 5, and a 4-(dimethylamino)phenyl or 4-(pyrrolidin-1-yl)phenyl group as a cap substructure generated highly potent hydroxamic acid-based HDAC inhibitors 5a and 5b.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Benzamides / chemical synthesis*
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Benzamides / chemistry
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Benzamides / pharmacology
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Binding Sites
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Histone Deacetylase Inhibitors*
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Humans
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology
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Models, Molecular
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Protein Binding
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Structure-Activity Relationship
Substances
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4-dimethylamino-N-(4-(2-hydroxycarbamoylvinyl)benzyl)benzamide
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Antineoplastic Agents
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Benzamides
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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N-(4-(2-hydroxycarbamoylvinyl)benzyl)-4-pyrrolidin-1-ylbenzamide