DERIVATIVES OF HETEROARYL-ALKYLCARBAMATES, METHODS FOR THEIR PREPARATION AND USE THEREOF AS FATTY ACID AMIDO HYDROLASE ENZYME INHIBITORS

摘要

The present invention is directed to compounds and compositions for the treatment of neurological diseases that cause neurogenic and neuropathic pain, inflammatory diseases, renal ishaemia, cardiovascular disease and other pathologies caused by the presence of endogenous cannabinoids and or other substrates resulting from the metabolic activities of fatty acid amido hydrolase (FAAH). These compounds are represented by the formula wherein A is selected from the group comprising X, Y or Z, and; X represents a methylene group optionally substituted by one or two C_1-6-alkyl, C_3-7-cycloalkyl or C_3-7-cycloalkyl-C_1-3-alkylene groups; Y represents either a C₂-alkenylene group optionally substituted by one or two C_1-6-alkyl, C_3-7-cycloalkyl or C_3-7-cycloalkyl-C_1-3-alkylene groups; or a C₂-alkynylene group; Z represents a group of formula: m represents an integer ranging from 1 to 5; p and q represent integers and are defined such that p+q is a number ranging from 1 to 5; n represents an integer ranging from 1 to 7; R₁ represents an R₂ group optionally substituted by one or more R₃ and/or R₄ groups; R₂ represents a group chosen from a pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, naphthyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, 1-oxo-3,4-dihydroisoquinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, naphthyridinyl, benzofuranyl, dihydrobenzofuranyl, benzothienyl, dihydrobenzothienyl, indolyl, indolinyl, indazolyl, isoinR₅R₆, -O-(C_1-3-alkylene)-O- or phenyl groups, the phenyl group optionally being substituted by one or more halogen atoms; R₃ represents a group chosen from halogen atoms or cyano, nitro, C_1-6-alkyl, C_3-7-cycloalkyl, C_1-6-alkoxy, hydroxyl, C_1-6-thioalkyl, C_1-6-fluoroalkyl, C_1-6-fluoroalkoxy, C_1-6-fluorothioalkyl, NR₅R₆, NR₅COR₆, NR₅CO₂R₆, NR₅SO₂R₆, COR₅, CO₂R₅, CONR₅R₆, SO₂R₅, SO₂N. R₄ represents a group chosen from phenyl, phenyloxy, benzyloxy, naphthyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl groups; it being possible for the R₄ group or groups to be substituted by one or more R₃ groups which are identical to or different from one another; R₅ and R₆ represent, independently of one another, a hydrogen atom or a C_1-6-alkyl group or form, with the atom or atoms which carry them, a ring chosen from an azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, azepine or piperazine ring, this ring optionally being substituted by a C_1-6-alkyl or benzyl group; R₇ represents a hydrogen atom or a C_1-6-alkyl group, and R₈ represents a hydrogen atom or a C_1-6-alkyl, C_3-7-cycloalkyl or C_3-7-cycloalkyl-C_1-3-alkylene group; a salt thereof, or a hydrate or a solvate of said compound or said salt.