New 4,5-diphenyl-2-oxazolecarboxamide derivatives useful for treating eating disorders, gastrointestinal disorders, inflammations, immunological diseases, psychoses, alcohol and nicotine dependence

摘要

4,5-Diphenyl-2-oxazolecarboxamide derivatives (I) are new. 4,5-Diphenyl-2-oxazolecarboxamide derivatives of formula (I) and their acid addition salts, hydrates and solvates are new. R 1H or 1-4C alkyl; R 24-10C alkyl; 3-12C nonaromatic carbocyclic optionally substituted with 1-4C alkyl; 1,2,3,4-tetrahydro-1- or -2-naphthyl; 5- to 7-membered heterocyclic containing 1 O or 1 S optionally substituted with 1-4C alkyl; 5- to 7-membered heterocyclic containing 1 N, N-substituted with 1-4C alkyl, phenyl, benzyl, 1-4C alkoxycarbonyl or 1-4C alkanoyl; 1-3C alkylene substituted with 3-12C nonaromatic carbocyclic optionally substituted with 1-4C alkyl; phenyl(1-3C)alkylene optionally substituted on alkylene with Me or 1-4C alkoxycarbonyl and optionally substituted on phenyl with halo, 1-4C alkyl, CF 3, 1-4C alkoxy or OCF 3; or NR 9R 10; or NR 1R 21-piperazinyl or 1,4-diazepan-1-yl 4-substituted with phenyl or benzyl; piperidino or pyrrolidino substituted with 1-2 phenyl, benzyl (both optionally substituted with halo, Me, OH, OMe, CN, acetyl or COOMe), 1-4C alkyl, OH, CN, 1-3C alkanoyl, 1-4C alkoxycarbonyl, 1-4C alkoxycarbonylamino, CONR 11R 12or NR 11R 12; or spiro[1H-indene-1,4'-piperidine] or 3H-spiro[2-benzofuran-1,4'-piperidine] optionally substituted with oxo; R 3-R 8H, halo, 1-6C alkyl, 1-6C alkoxy, CF 3or SO nAlk; R 9H or Me; R 10phenyl, 3-10C cycloalkyl (both optionally substituted with halo or 1-4C alkyl) or 3-6C alkyl; or NR 9R 105- to 11-membered (un)saturated heterocycle optionally bridged, spiro and/or containing another heteroatom (O or N), optionally substituted with OH, 1-4C alkyl, 1-4C alkoxycarbonyl or phenyl optionally substituted with halo or 1-4C alkyl; R 11, R 12H or 1-4C alkyl; or NR 11R 123- to 7-membered heterocycle optionally containing another heteroatom (O or N), optionally substituted with Me; n : 0-2; Alk : 1-4C alkyl. Provided that R 3-R 8are not all H. Independent claims are also included for: (1) preparation of (I); and (2) 4,5-diphenyl-2-oxazolecarboxylic acid derivatives of formula (II). X : halo, OH, 1-4C alkyl or benzyl. [Image] [Image] ACTIVITY : Antiinflammatory; Neuroleptic; Antialcoholic; Antismoking; Tranquilizer; Antidepressant; Antimigraine; Anticonvulsant; Antiparkinsonian; Nootropic; Vasotropic; Analgesic; Anorectic; Antidiabetic; Antilipemic; Antidiarrheic; Antiemetic; Antibacterial; Immunosuppressive; Hepatotropic; Antiasthmatic; Ophthalmological; Antiarthritic; Neuroprotective; Virucide; Cerebroprotective; Cytostatic; Osteopathic. MECHANISM OF ACTION : Cannabinoid CB 1receptor ligand. (I) have high affinity for CB 1receptor (IC50 1 mu M to 1 nM) under the experimental conditions described in FEBS Letters, 350, 240 (1994).