Fatty acid amide hydrolase (FAAH) is an intracellular serine hydrolase responsible for the deactivation of the endocannabinoid anandamide (AEA), which is involved in the regulation of several physiological functions and mammalian behaviors, including pain, inflammation and cognitive/emotional state.These findings have triggered a growing interest in the discovery of several chemically distinct classes of FAAH inhibitors, such as the O-aryl carbamates and the piperidine/piperazine ureas.As a part of our research program aimed at further exploring the class of O-biphenyl carbamates, represented by URB597 (R = 3'-CONH2), we conducted a focused structure-activity relationship (SAR) study by exploring the replacement of the distal phenyl ring of URB597 with N-heterocyclic rings, such as pyrrolidynyl, piperidinyl, morpholinyl and piperazinyl derivatives.Herein, the results of this SAR exploration will be presented which allowed the identification of novel and potent FAAH inhibitors with improved kinetic solubility and plasma stability.

Structure-activity relationship studies on <i>O</i>-[3-(heterocyclyl)phenyl] carbamate FAAH inhibitors

248th National Meeting (2014)

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Structure-activity relationship studies on O-[3-(heterocyclyl)phenyl] carbamate FAAH inhibitors