Abstract
The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs is described. Some of these compounds were shown to inhibit HDAC1 with IC(50) values below the micromolar range, induce hyperacetylation of histones, upregulate expression of the tumor suppressor p21(WAF1/Cip1), and inhibit proliferation of human cancer cells. In addition, certain compounds of this class were active in several human tumor xenograft models in vivo.
MeSH terms
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Aniline Compounds / chemical synthesis*
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Aniline Compounds / chemistry
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Aniline Compounds / pharmacology*
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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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Breast / cytology
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Breast / drug effects
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Cell Line
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Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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HCT116 Cells
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Histone Deacetylase 1
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Histone Deacetylase Inhibitors*
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Structure-Activity Relationship
Substances
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Aniline Compounds
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Antineoplastic Agents
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Benzamides
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Imidazoles
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HDAC1 protein, human
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Histone Deacetylase 1