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.