N-[(1,5-diphenyl-1H-pyrazol-3-yl)methyl]sulfonamide derivatives antagonists of the CB1 cannabinoids receptors

摘要

Pyrazole compounds (I) in the basic or acid additive salt form, hydrate or solvate forms, are new. Pyrazole compounds of formula (I) in the basic or acid additive salt form, hydrate or solvate forms, are new. R 11-12C alkyl (optionally substituted by F, OH, 1-4C alkoxy, 1-4C alkylthio, phenoxy, -O-CF 3, -OCHF 2, -S-CHF 2, -SCF 3), T, methyl (optionally substituted by T), benzyl/benzhydryl/benzydrylmethyl (optionally substituted by halo, OH, methylenedioxy, CN, NO 2, 1-4C alkylcarbonyl or Alk, O-Alk, S(O) n-Alk or OS(O) nAlk), phenyl (substituted by a heterocyclic radical such as pyrrolyl, imidazolyl, pyridyl or pyrrazolyl (all optionally substituted by halo or 1-4C alkyl), phenyl/phenoxy (where phenyl group is optionally substituted by halo, OH, methylenedioxy, CN, NO 2, 1-4C alkylcarbonyl or -Alk, O-Alk, S(O) n-Alk or OS(O) n-Alk) and optionally substituted by halo, OH, methylenedioxy, CN, NO 2, 1-4C alkylcarbonyl or Alk, O-Alk, S(O) nAlk or OS(O) n-Alk), T 1, tetrahydronaphthalenyl/naphthyl (optionally substituted by halo, 1-4C alkyl, di(1-4C) alkylamino or CF 3) or 2,3-dihydrobenzofuran-yl (optionally substituted by 1-4C alkyl, indol-2-yl or N-methylindol-2-yl); T : 3-12C non-aromatic carbocyclic radical (optionally substituted by 1-4C alkyl, 1-4C alkoxy, 1-4C alkylthio, F, OH, CF 3, -CHF 2, -O-CF 3, -O-CHF 2, -S-CF 3or -S-CHF 2); T 1thienyl, furyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl, pyridyl (all optionally substituted by the halo, 1-4C alkyl or CF 3); R 2H, 1-4C alkyl or 1-4C alkylsulfonyl; R 3CN, OH, 1-4C alkoxy, cyanomethyl, hydroxymethyl, 1-4C alkoxymethyl, fluoromethyl, tetrazolylmethyl, N-(methyl)tetrazolylmethyl, tetrazolyl, N-(methyl)tetrazolyl, CONR 6R 7, -CH 2S(O) n(1-4C)alkyl, -COOR 8or CH 2NR 6R 7; R 4, R 5phenyl (optionally substituted by halo, 1-7C alkyl (optionally substituted by F, OAlk, S(O) nAlk or OS(O) nAlk)); either R 6, R 7H or 1-4C alkyl; or NR 6R 7heterocyclic radical such as pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl (optionally substituted by 1-4C alkyl); R 81-4C alkyl; n : 0-2; and Alk : 1-4C alkyl (optionally substituted by F). Independent claims are included for: (1) preparation of (I); and (2) drug, comprising (I). [Image] ACTIVITY : Neuroleptic; Antiaddictive; Nootropic; Tranquilizer; Neuroprotective; Metabolic; Anorectic; Antidiabetic; Antilipemic; Analgesic; Gastrointestinal-Gen; Antiemetic; Antidiarrheic; Antiulcer; Hepatotropic; Immunomodulator; Antiarthritic; Antirheumatic; Antiinflammatory; Antiparkinsonian. MECHANISM OF ACTION : Cannabinoid (CB1) receptor antagonist.