α-Keto heterocycle inhibitors of fatty acid amide hydrolase: carbonyl group modification and α-substitution

Two sets of novel analogues of the recently disclosed α-keto heterocycle inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for regulation of endogenous oleamide and anandamide, were synthesized and evaluated in order to clarify a role of the electrophilic carbonyl group and structural features important for their activity. Both the electrophilic carbonyl and the degree of α-substitution markedly affect inhibitor potency.