Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors

5-(Trifluoroacetyl)thiophene-2-carboxamides were found to be potent and selective class II HDAC inhibitors. This paper describes their further development and the investigation on the cause for the lack of cell-based activity. A rapid screening assay was set up which enabled the identification of more metabolic stable compounds as potent and selective class II HDAC inhibitors.

Graphical abstractThe cause for the lack of cellular activity of the 5-(trifluoroacetyl)-thiophene-2-carboxamides was investigated. A rapid screening assay identified analogs as potent, selective, and metabolically stable class II HDAC inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide