Abstract
Trifluoroacetylthiophene carboxamides have recently been reported to be class II HDAC inhibitors, with moderate selectivity. Exploration of replacements for the carboxamide with bioisosteric pentatomic heteroaromatic like 1,3,4-oxadiazoles, 1,2,4-oxadiazoles and 1,3-thiazoles, led to the discovery that 2-trifluoroacetylthiophene 1,3,4-oxadiazole derivatives are very potent low nanomolar HDAC4 inhibitors, highly selective over class I HDACs (HDAC 1 and 3), and moderately stable in HCT116 cell culture.
MeSH terms
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Combinatorial Chemistry Techniques
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Drug Design
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HCT116 Cells
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Histone Acetyltransferases / antagonists & inhibitors
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Histone Deacetylase Inhibitors*
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Histone Deacetylases / classification
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Humans
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Molecular Structure
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Oxadiazoles / chemical synthesis*
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Oxadiazoles / chemistry
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Oxadiazoles / pharmacology*
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Structure-Activity Relationship
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Thiophenes / chemical synthesis*
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Thiophenes / chemistry
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Thiophenes / pharmacology*
Substances
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Histone Deacetylase Inhibitors
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Oxadiazoles
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Thiophenes
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Histone Acetyltransferases
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Histone Deacetylases