Peripherally restricted faah inhibitors

Abstract

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.