DIBENZOCYCLOHEPTANONE DERIVATIVES AND PHARMACEUTICAL AGENTS CONTAINING SAID COMPOUNDS

摘要

Dibenzocycloheptanone derivatives (I) and their optical isomers, salts or solvates, are new. Dibenzocycloheptanone derivatives of formula (I) and their optical isomers, salts or solvates are new. Either X, Y 1> : CH 2, O, S, SO, SO 2 or NR 5>; or -X-Y 1>- : -CH 2-CH 2- or -CH=CH-; R 1> : RO, NR 6>R 7>, tetrazolo or NR 8>CONR 13>R 14>; R : 1-6C-alkyl optionally substituted with 1, 2 or 3 OH or 1-6C-alkoxy, 1-6C-alkyl (optionally substituted with optionally saturated, aromatic or non-aromatic heterocycle with 5 or 6 ring atoms and containing 1-3 heteroatoms of O, N or S, where the heterocycle is optionally substituted by 1 or 2 OH, 1-6C-alkoxy or 1-6C-alkyl and can be condensed with a phenyl ring or an optionally saturated carbocycle with 5 or 6 ring atoms), a non-aromatic heterocycle with 5 or 6 ring atoms having 1 or 2 heteroatoms of O or N, 1-6C-alkyl, H, 1-6C-alkyl substituted with NR 6>R 7>, CF 3SO 2-, 1-6C-alkylcarbonyloxy-1-6C-alkyl, or 3-7C-cycloalkyl-1-6C-alkyl (in which the cycloalkyl residue optionally contains 1 or 2 OH, 1-6C-alkoxy or 1-6C-alkyl); R 2> : H or 1-6C-alkyl; R 3> : substituted benzene group of formula (a)-(c), substituted cyclohexane group of formula (d), NH-1-6C-alkylen-NR 6>R 7> or tetrazolo; R 4> : H, halo or 1-6C-alkyl; R 5>-R 7> : H or 1-6C-alkyl (optionally substituted by 1, 2 or 3 OH or 1-6C-alkoxy); R 8> : H or 1-6C-alkyl; R 9>-R 11> : H, NH 2, mono-1-6C-alkylamino, di-1-6C-alkylamino, 1-6C-alkyl, 1-6C-alkoxy, OH, halo, 1-6C-alkyl (optionally substituted by 1, 2 or 3 halo), CONR 6>R 7> or NO 2; R 12> : H or NH 2; and either R 13>, R 14> : H or 1-6C-alkyl; or R 13>R 14>N : non-aromatic heterocycle with 5 or 6 ring atoms and having 1 or 2 heteroatoms of O or N. [Image] [Image] ACTIVITY : Immunomodulator; Antiinflammatory; Antiasthmatic; Antiallergic; Antiarthritic; Antirheumatic; Antiarteriosclerotic; Gastrointestinal-Gen.; Antipsoriatic; Dermatological; Cytostatic; Antibacterial; Osteopathic; Analgesic; Anti-HIV; Cardiant; Antidiabetic; Vasotropic; Endocrine-Gen.; Respiratory-Gen.; Neuroprotective; Anabolic; Nootropic; Cerebroprotective; Hepatotropic; Antiulcer; Cardiovascular-Gen.; CNS-Gen.; Virucide. MECHANISM OF ACTION : Interleukin-1beta inhibitor; TNF-alpha inhibitor. The ability of (I) to inhibit TNF-alpha was tested. The results showed that 2-(2-amino-phenylamino)-7-(2,3-dihydroxy-propoxy)-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one exhibited IC 5 0 value of greater than 5.