Novel trifluoroacetophenone derivatives as malonyl-CoA decarboxylase inhibitors.
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.
Wallace
David M
DM
Department of Chemistry, Chugai Pharma USA, LLC., 6275 Nancy Ridge Dr., San Diego, CA 92121, USA. davidmw@san.rr.com
Haramura
Masayuki
M
Cheng
Jie-Fei
JF
Arrhenius
Thomas
T
Nadzan
Alex M
AM
D000098:Acetophenones / Q000138:chemical synthesis* / Q000494:pharmacology*; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008316:Malonyl Coenzyme A / Q000378:metabolism; D020005:Propanols / Q000737:chemistry; D013329:Structure-Activity Relationship; D006845:Hydrocarbons, Fluorinated
D000098:Acetophenones; D002262:Carboxy-Lyases; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D008316:Malonyl Coenzyme A; D020005:Propanols; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated; C021532:malonyl-CoA decarboxylase