Abstract
We have identified a series of diphenylmethylene hydroxamic acids as novel and selective HDAC class IIa inhibitors. The original hit, N-hydroxy-2,2-diphenylacetamide (6), has sub-micromolar class IIa HDAC inhibitory activity, while the rigidified oxygen analogue, N-hydroxy-9H-xanthene-9-carboxamide (13), is slightly more selective for HDAC7 with an IC(50) of 0.05muM. Substitution of 6 allows for the modulation of selectivity and potency amongst the class IIa HDAC isotypes.
MeSH terms
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Cell Line
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Diphenylacetic Acids / chemical synthesis
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Diphenylacetic Acids / chemistry*
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Diphenylacetic Acids / pharmacology
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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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Histone Deacetylases / metabolism
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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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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / metabolism
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Structure-Activity Relationship
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Xanthenes / chemical synthesis
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Xanthenes / chemistry*
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Xanthenes / pharmacology
Substances
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Diphenylacetic Acids
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Enzyme Inhibitors
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Hydroxamic Acids
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N-hydroxy-2,2-diphenylacetamide
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N-hydroxy-9H-xanthene-9-carboxamide
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Protein Isoforms
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Xanthenes
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Histone Deacetylases