Piperazinyl and piperidinyl ureas as modulators of fatty...

C - Chemistry – Metallurgy – 07 – D

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C07D 295/20 (2006.01) A61P 25/04 (2006.01) A61P 25/22 (2006.01) A61P 25/28 (2006.01) C07C 275/28 (2006.01) C07D 215/12 (2006.01) C07D 239/42 (2006.01) C07D 241/42 (2006.01) C07D 317/58 (2006.01) C07D 401/12 (2006.01) C07D 405/12 (2006.01) C07D 417/12 (2006.01)

Patent

CA 2596393

Compounds of formula (I) : wherein, Z is -N-or>CH; R1 is -H or -C1-4alkyl; Ar1 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 Ra moieties; Wher each Ra 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(Rb)Rc, -SO2NRbRc, -NRbSO2Rc, - C(=O)NRbRc, -NO2, and -CN, wherein Rb and Rc are each independently -H or -C1- 4alkyl; and Ar2 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).

La présente invention concerne des composés de formule (I) ; dans laquelle Z est N ou CH ; R1 est H ou un alkyle enC1-4 ; Ar1 est le 2-thiazolyle, le 2-pyridyle, le 3-pyridyle, le 4-pyridyle, le 2-pyrimidinyle, le 4-pyrimidinyle, le 5-pyrimidinyle, ou un phényle, chacun étant non substitué ou substitué sur un élément d~un anneau de carbone avec un ou deux fragments Ra ; dans laquelle chacun des fragments Ra est indépendamment choisi dans le groupe constitué par un alkyle enC1-4, un aclényle enC2-4, OH, OC1-4alkyle, halo, CF3, OCF3, SCF3, SH, S(O)0-2C1-4alkyle, OSO2C1-4alkyle,-CO2C1-4alkyle, CO2H, COC1-4alkyle, N(Rb)Rc, SO2NRbRc, NRbSO2Rc, C(=O)NRbRc, NO2, et CN, dans laquelle Rb et Rc sont chacun indépendamment H ou un alkyle en C1-4alkyle ; et Ar2 est défini dans les revendications et sont utiles en tant que inhibiteurs du FAAH. Ces composés peuvent être employés dans des compositions pharmaceutiques et des procédés pour le traitement de maladies, de troubles et d~états de santé médiés par l~activité de l~amide hydrolase d~acides gras (FAAH). Ainsi, les composés peuvent être administrés pour traiter par exemple l~anxiété, la douleur, l~inflammation, les troubles du sommeil, les troubles de l~alimentation ou les troubles de la mobilité (tels que la sclérose en plaques).

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