Abstract
This communication highlights the development of a nicotinamide series of histone deacetylase inhibitors within the benzamide structural class. Extensive exploration around the nicotinamide core led to the discovery of a class I selective HDAC inhibitor that possesses excellent intrinsic and cell-based potency, acceptable ancillary pharmacology, favorable pharmacokinetics, sustained pharmacodynamics in vitro, and achieves in vivo efficacy in an HCT116 xenograft model.
MeSH terms
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6-Aminonicotinamide / analogs & derivatives*
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6-Aminonicotinamide / chemical synthesis
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6-Aminonicotinamide / pharmacology*
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Animals
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Area Under Curve
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Benzamides / chemistry
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Biological Availability
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Cell Line, Tumor
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Cell Membrane Permeability / drug effects
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Dogs
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Drug Design
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Half-Life
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Histone Deacetylase Inhibitors*
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Humans
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Isoenzymes / antagonists & inhibitors
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Models, Molecular
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Neoplasm Transplantation
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Protein Binding
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Rats
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Benzamides
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Isoenzymes
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6-Aminonicotinamide