Novel trifluoroacetophenone derivatives as malonyl-CoA decarboxylase inhibitors

A series of trifluoroacetophenone derivatives were prepared and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Several of the ‘reverse amide’ analogs were found to be potent inhibitors of MCD enzyme activity. The trifluoroacetyl group may interact with the MCD active site as the hydrate, which can be stabilized with electron-withdrawing groups.