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Bioorg Med Chem Lett. 2007 Feb 15;17(4):1127-30. Epub 2007 Jan 17.

Novel trifluoroacetophenone derivatives as malonyl-CoA decarboxylase inhibitors.

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  • 1Department of Chemistry, Chugai Pharma USA, LLC., 6275 Nancy Ridge Dr., San Diego, CA 92121, USA.


A series of trifluoroacetophenone derivatives were prepared and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Some 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 in a similar fashion to the hexafluoroisopropanol analogs reported previously. Adding electron-withdrawing groups to the phenyl ring stabilizes the hydrated species and enhances this interaction.

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