Patent FR-2908766-A1 (FR)
Title: New pyrrole derivatives are cannabinoid receptor antagonists useful to prevent/treat psychiatric disorders, cognitive disorders, neurodegenerative diseases, metabolic disorders, dyslipidemia, pain, ulcer and tobacco weaning
Inventor: BARTH FRANCIS
IPC: A61K31/40
Filed: 2006-11-20
Abstract: Pyrrole derivatives (I), in the form of base or acid addition salts, hydrates or solvates, are new. Pyrrole derivatives of formula (I), in the form of base or acid addition salts, hydrates or solvates, are new. A : 1-6C alkylene (optionally substituted by 1-3C alkyl) or a phenyl moiety of formula (Iz); m : 0-2; p : 0-1; either R 1H or 1-4C alkyl; R 23-10C alkyl (optionally substituted by CF 3), 3-12C non-aromatic carbocyclic (optionally substituted by 1-4C alkyl, OH, CN, 1-4C alkoxy or -COR 12), indanyl, 1,2,3,4-tetrahydronaphtalenyl -1 or -2, 5-7 membered mono-oxygenated or mono-sulfidized heterocyclic (optionally substituted by 1-4C alkyl), 5-7 membered mono-nitrogenized heterocyclic (optionally substituted by 1-4C alkyl, the nitrogen atom is substituted by 1-4C alkyl, 1-4C alkoxycarbonyl, 1-4C alkanoyl or phenyl or benzyl( both optionally substituted by halo, 1-4C alkyl, CF 3, OH or 1-4C alkoxy), benzothiophenyl or indolyl (both optionally substituted by 1-4C alkyl), 1-3C alkylene carrying 3-10C non-aromatic carbocyclic radical (optionally substituted by 1-4C alkyl, OH, 1-4C alkoxy, CN, or -COR 12), 1-3C alkylene carrying a 5-7 membered hetero(aromatic)cyclic radical (optionally substituted by 1-4C alkyl), 1-3C alkylene (optionally substituted by OH, Me or OMe, or -COR 12) carrying an indolyl or a benzothiophenyl radical (optionally substituted by 1-4C alkyl), 1-3C alkylene carrying 1-4C alkylthio group), phenyl-1-3C alkylene (optionally substituted on alkylene by Me, OH, hydroxymethyl, OMe, methoxymethyl or COR 12, and optionally substituted on the phenyl by halo or 1-4C alkyl, CF 3, 1-4C alkoxy or CF 3), benzydryl or benzydrylmethyl or NR 10R 11; or NR 1R 2morpholinyl, piperazin-1-yl or 1,4-diazepan-1-yl (optionally substituted by phenyl, benzyl, benzodioxolyl, benzodioxolylmethyl, tetrahydrofuranylcarbonyl or COR 12 or -CH 2COR 12), piperidin-1-yl or pyrrolidin-1-yl (optionally mono or gem disubstituted by F, or phenyl, benzyl, piperidin-1-yl, pyrrolidin-1-yl, 1-4C alkyl, OH, CN or COR 12, -NR 13R 14, -NHCOR 15, -CH 2COR 12, -SO 2-Alk or -SO 2-NR 13R 14, where phenyl and benzyl are optionally substituted by halo, Me, -CF 3, hydrolyl or 1-4C alkoxy); R 3-R 8H or halo, 1-5C alkoxy, S(O) n-Alk2, -OS(O) n-Alk2 or 1-7C alkyl (optionally substituted by F, O-Alk2, S(O) nAlk2 or OS(O) nAlk); R 9OH, CN, -COOH, -NR 13R 14, -CONR 13R 14, -CONHNH 2, -CONHOH, -CONHSO 2-Alk, -S(O) n-Alk, -SO 2CF 3, -SO 2-NR 13R 14, -NHSO 2-Alk, -NHSO 2CF 3, -NH-SO 2-NR 13R 14 or 3-hydroxy-3H-imidazole-4-yl, 1H-tetrazol-5-yl, 3-hydroxy-1H-pyrazol-5-yl, 3-hydroxy-isoxazol-5-yl, 3-hydroxy-isothiazol-5-yl, 2-oxo-2,3-dihydro-2lambda-4-[1,2,3,5]oxathiadiazole-4-yl, 5-hydroxy-isoxazole-4-yl or 2-Hydroxy-2H-pyrazole-3-yl; either R 10H or Me; R 113-6C alkyl, phenyl or 3-10C cycloalkyl, where the phenyl and 3-10C cycloalkyl are optionally substituted by halo, 1-4C alkyl or -CF 3; or NR 10R 114-11 membered heterocyclic radical optionally comprising a spirannic carbon and optionally containing a second heteroatom of O or N, optionally substituted by OH, 1-4C alkyl, 1-4C alkoxycarbonyl or phenyl (optionally substituted by halo or 1-4C alkyl); R 121-4C alkyl, phenyl, benzyl, 1-4C alkoxy, CF 3 or NR 13R 14; either R 13, R 14H or 1-4C alkyl; NR 13R 144-7 membered heterocyclic (optionally containing second heteroatom N, O or S); R 15-14C alkyl or CF 3; n : 0-2; Alk2 : 1-4C alkyl (optionally substituted by F); and Alk : 1-4C alkyl. Independent claims are included for: (1) the preparation of (I); and (2) a pyrrole derivative of formula (IIa). X : halo, OH, 1-4C alkoxy or benzyloxy. [Image] [Image] [Image] ACTIVITY : Neuroleptic; Nootropic; Tranquilizer; Neuroprotective; Metabolic; Anorectic; Antidiabetic; Analgesic; Antianginal; Antilipemic; Gastrointestinal-Gen; Antiemetic; Antidiarrheic; Antiulcer; Hepatotropic; Immunomodulator; Antiarthritic; Antirheumatic; Antiinflammatory; Antiparkinsonian; Antismoking; Antidepressant; Hypnotic; Antialcoholic; Antimigraine; Anticonvulsant; Muscular-Gen.; Inotropic; Vasotropic; Cerebroprotective; Antiaddictive; Eating-Disorders-Gen; Cardiovascular-Gen; Uropathic; Virucide; Endocrine-Gen; Hypertensive; Antiarteriosclerotic; Antibacterial; Immunosuppressive; Antiasthmatic; Respiratory-Gen; Ophthalmological; Antiinfertility; Gynecological; CNS-Gen; Osteopathic. MECHANISM OF ACTION : Cannabinoid CB 1 receptor antagonist.