Piperazinyl and piperidinyl ureas as modulators of fatty acid amide hydrolase

Abstract

Compounds of formula (I): wherein, Z is -N-or>CH; R<1> is -H or -C1-4alkyl; Ar<1> is 2-thiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-primidinyl, 5-pyrimidinyl, or phenyl, each unsubstituted or substituted at a carbon ring member with one or two R moieties; where each R moiety is independently selected from the group consisting of -C1-4alkyl, -C2-4alkenyl, -OH, -OC1-4alkyl, halo, -CF3, -OCF3, -SCF3, -SH, -S(O)0-2C1-4alkyl, -OSO2C1-4alkyl, -CO2C1-4alkyl, -CO2H, -COC1-4alkyl, -N(R)R<c>, -SO2NRR<c>, -NRSO2R<c>, -C(=O)NRR<c>, -NO2, and -CN, wherein R and R<c> are each independently -H or -C1-4alkyl; and Ar<2> is defined in the claims are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application 60 / 640,869, filed December 30, 2004 technical field [0003] The present invention relates to certain piperazinyl urea and peperidinylurea compounds, pharmaceutical compositions containing them, and their use in the treatment of disease states, disorders and conditions mediated by fatty acid amide hydrolase (FAAH) activity Methods. Background technique [0004] The medicinal benefits of the cannabis plant have been known for centuries. The main bioactive constituents of cannabis are △ 9 - Tetrahydro-cannabinol (THC). The discovery of THC eventually led to the identification of two endocannabinoid (cannabinoid) receptors responsible for its pharmacological effects, known as CB 1 and CB 2 (Goya, Exp. Opin. Ther Patents 2000, 10, 1529). These findings not only establish THC's site of action, but also interrogate endogenous agonists, or "endocannabinoid...

AI Technical Summary

Problems solved by technology

Experiments with FAAH- / - mice showed reduced responses in nociception tests, but not catalepsy, hypothermia or enhanced feeding behavior (Cravatt, Proc. Natl. Acad. Sci. USA 2001, 98(16) , 9371)

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