New N-(4-cyano-1H-pyrazol-3-yl)-methylamine derivatives, are cannabinoid CB1 receptor antagonists, useful e.g. for treating psychiatric, neurodegenerative or metabolic disorders

摘要

N-Substituted N-(4-cyano-1H-pyrazol-3-yl)-methylamine derivatives (I) are new. Pyrazole derivatives of formula (I) and their acid addition salts, hydrates and solvates are new. X : CO, CONR 5, CSNH or SO 2NR 5; R 11-12C alkyl (optionally substituted (os) by one or more of F, alkoxy or Q); 3-12C non-aromatic carbocyclyl (os by one or more of halo, A or OA, or Ph or SO 2Ph (both os by halo)); phenyl (os by one or more of halo, A, OA, OCH 2O, NHA, NA 2, CN, NO 2, alkanoyl or alkoxycarbonyl, or Ph, OPh, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, thiadiazolyl or pyridyl (all os by one or more alkyl)); tetrahydronaphthyl, 2,3-dihydrobenzofuranyl or 3,4-dihydro-2H-pyranyl (all os by one or more alkyl); or pyrrolyl, imidazolyl, pyrazolyl, furyl, thienyl, oxazolyl, pyridyl, indolyl or 1,3-benzothiazolyl (all os by one or more of halo, A or OA); Q : phenyl, phenoxy, phenylthio, phenylsulfonyl, pyridyloxy, pyrrolyl, imidazolyl, pyrazolyl, furyl, thienyl, oxazolyl or pyridyl (all os by one or more of halo, A and OA); R 2H or alkyl; R 3, R 4phenyl (os by one or more of halo, A and OA); R 5H or alkyl; A : alkyl (os by one or more F); alkyl moieties have 1-4C unless specified otherwise. An independent claim is included for the preparation of (I). [Image] ACTIVITY : Neuroleptic; Antiaddictive; Nootropic; Neuroprotective; Anorectic; Antidiabetic; Antilipemic; Analgesic; Antiemetic; Antidiarrheic; Antiulcer; Hepatotropic; Immunosuppressive; Antirheumatic; Antiarthritic; Antiparkinsonian; Antismoking; Tranquilizer; Antialcoholic; Antimigraine; Anticonvulsant; Vasotropic; Cerebroprotective; Cardiant; Hypertensive; Antiarteriosclerotic; Antibacterial; Antiasthmatic; Antiinflammatory; Antiinfertility; Tocolytic; Virucide; Cytostatic; Osteopathic. MECHANISM OF ACTION : Cannabinoid CB 1receptor antagonist.