University of California

Università Degli Studi Di Parma

Universita Degli Studi Di Urbino

Università Degli Studi Di Urbino "carlo Bo"

Universita Degl Studi Di Parma

Andrea Duranti

Daniele Piomelli

Giorgio Tarzia

Marco Mor

Andrea Tontini

Guillermo Moreno-Sanz

Jason R Clapper

Georgio Tarzia

Jason Clapper

Compounds and pharmaceutical compositions are contemplated that inhibit N-acyl-ethanolamine-hydrolyzing acid amidase (NAAA) to so increase the concentration of the substrate of NAAA, palmitoylethanolamide (PEA). NAAA inhibition is contemplated to be effective to alleviate conditions associated with a reduced concentration of PEA. Among other uses, various NAAA inhibitors are especially contemplated as therapeutic agents in the treatment of inflammatory diseases.

Compositions and methods of inhibiting N-acylethanolamine-hydrolyzing acid amidase

Peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH) are provided. The compounds can suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). Despite their relative inability to access brain and spinal cord, the compounds attenuate behavioral responses indicative of persistent pain in rodent models of inflammation and peripheral nerve injury, and suppresses noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CBi receptor blockade prevents these effects. Accordingly, the invention also provides methods, and pharmaceutical compositions for treating conditions in which the inhibition of peripheral FAAH would be of benefit. The compounds of the invention are according to the formula (I): in which Ris a polar group. In some embodiments, Ris selected from the group consisting of hydroxy and the physiologically hydro lysable esters thereof. Rand Rare independently selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbyl; each Ris independently selected from the group consisting of halogen and substituted or unsubstituted hydrocarbyl and n is an integer from 0 to 4; each Ris independently selected from the group consisting of halo and substituted or unsubstituted hydrocarbyl and m is an integer from 0 to 3; and Ris substituted or unsubstituted cyclohexyl; and the pharmaceutically acceptable salts thereof. 

Peripherally restricted FAAH inhibitors

Fatty acid amide hydrolase inhibitors of the Formula: are provided wherein X is NH, CH, O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted biphenylyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted phenyl; substituted or unsubstituted terphenylyl; substituted or unsubstituted cycloalkyl, heteroaryl, or alkyl; and Rand Rare independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and substituted or unsubstituted phenyl, substituted or unsubstituted biphenylyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; with the proviso that if Z is O, one of Rand Ris absent, and that if Z is N, optionally Rand Rmay optionally be taken together to form a substituted or unsubstituted N-heterocycle or substituted or unsubstituted heteroaryl with the N atom to which they are each attached. Pharmaceutical compositions comprising the compounds of Formula I and methods of using them to inhibit FAAH and/or treat appetite disorders, glaucoma, pain, insomnia, and neurological and psychological disorders including anxiety disorders, epilepsy, and depression are provided.

Modulation of anxiety through blockade of anandamide hydrolysis

Growing community of inventors

Urbino, Italy

Andrea Duranti