Arachidonyl trifluoromethyl ketone

The first substrate analogue inhibitors of FAAH were reported in 1994. The anandamide analogues prepared represented three elasses of putative transition-state inhibitors a-trifluoromethyl ketones, a-ketoesters and a-ketoamides [62], In the initial sereening studies, it was found that the trifluoromethyl ketone eompounds tested were effeetive inhibitors of AEA hydrolysis. A selected set of a-keto esters also inhibited hydrolysis, while a-keto amides were ineffective. In particular, arachidonyl trifluoromethyl ketone (32), gave almost 100% inhibition of anandamide hydrolysis. A detailed investigation of the structural requirements for FAAH inhibition with a-trifluoromethyl ketones has been carried out by Roger and co-workers [63]. 

Arachidonyl trifluoromethyl ketone was reported to be a slow tight-binding inhibitor of a novel 85 kilodalton-(kDa) cytosolic human... 

Riendeau, D. Guay, J. Weech, P.K. Laliberte, F. Yergey, C.I. Desmarais, S. Perrier, H. Liu, S. Nicoll-Griffith, D. and Street, I.P. Arachidonyl trifluoromethyl ketone, a potent inhibitor of 85-kDa phospholipase A2, blocks production of arachidonate and 12-hydroxyeicosatetraenoic acid by calcium ionophore-challenged platelets. J Biol Chem 269(22) 15619-15624, 1994. 

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