Abstract
Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration of the 14 A internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis(aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, nonhydroxamic acid HDAC inhibitors.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Benzamides / chemical synthesis*
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Benzamides / chemistry
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Benzamides / pharmacology
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Catalytic Domain
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Cell Line
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Histone Deacetylase 1
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Histone Deacetylase Inhibitors*
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Histone Deacetylases / chemistry
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Histone Deacetylases / metabolism
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Humans
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Models, Molecular
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NADH, NADPH Oxidoreductases / antagonists & inhibitors*
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NADH, NADPH Oxidoreductases / chemistry
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NADH, NADPH Oxidoreductases / metabolism
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Benzamides
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Histone Deacetylase Inhibitors
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NADH, NADPH Oxidoreductases
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8-hydroxy-5-deazaflavin-NADPH oxidoreductase
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HDAC1 protein, human
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Histone Deacetylase 1
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Histone Deacetylases