Abstract
A series of hydroxamic acid-based HDAC inhibitors with an indole amide residue at the terminus have been synthesized and evaluated. Compounds with a 2-indole amide moiety have been found as the most active inhibitors among the different regioisomers. Introduction of substituents on the indole ring further improved the potency and generated a series of very potent inhibitors with significant antiproliferative activity. A representative compound in the series, 7b, has been found to be orally active in tumor growth inhibition model.
MeSH terms
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Amides / chemistry*
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Amides / pharmacology*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Histone Deacetylase Inhibitors*
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Humans
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology*
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Indoles / chemistry*
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Indoles / pharmacology*
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Inhibitory Concentration 50
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Amides
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Antineoplastic Agents
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Indoles
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indole