2-Trifluoroacetylthiophene oxadiazoles as potent and selective class II human histone deacetylase inhibitors

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 t...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2008-12, Vol.18 (23), p.6083-6087
Main Authors: MURAGLIA, Ester, ALTAMURA, Sergio, JONES, Philip, BRANCA, Danila, CECCHETTI, Ottavia, FERRIGNO, Federica, ORSALE, Maria Vittoria, PALUMBI, Maria Cecilia, ROWLEY, Michael, SCARPELLI, Rita, STEINKÜHLER, Christian
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Combinatorial Chemistry Techniques
Drug Design
General aspects
HCT116 Cells
Histone Acetyltransferases - antagonists & inhibitors
Histone Deacetylase Inhibitors
Histone Deacetylases - classification
Humans
Medical sciences
Molecular Structure
Oxadiazoles - chemical synthesis
Oxadiazoles - chemistry
Oxadiazoles - pharmacology
Pharmacology. Drug treatments
Structure-Activity Relationship
Thiophenes - chemical synthesis
Thiophenes - chemistry
Thiophenes - pharmacology
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Summary: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.
ISSN:0960-894X
0968-0896
1464-3405
1464-3391
DOI:10.1016/j.bmcl.2008.09.076