New dibenzocycloheptane compounds are tumor necrosis factor-alpha inhibitors useful to treat e.g. cancer, rheumatic arthritis, gout, septic shock, osteoporosis, naturopathic pain, HIV-propagation and periodontal diseases

摘要

Dibenzocycloheptane compounds (I) and their salt and solvate and its salts, are new. Dibenzocycloheptane compounds of formula (I) and their salt and solvate and its salts, are new. Either X, Y1 : CH 2, O, S, SO, SO 2or NR5; or X-Y1- : -(CH 2) 2- or -CH=CH-; R1 : H or 1-6C alkyl; R2 : H, halo or 1-4C alkyl-C?=C- (optionally substituted with amino group); R3 : -NH 2, phenyl compound of formula (a) or (b), cyclohexane compound of formula (c), -NH-1-6C alkylene-NH 2or halo; either R4 : H, halo or 1-6C alkyl; or CR3R4 : phenyl ring, 5-6 membered aromatic or non-aromatic heterocyclic ring with heteroatom such as N (where the heterocyclic ring is substituted with one or two 1-6C alkyl group or is condensed with a cyclohexyl group); R5, R6 : H or 1-6C alkyl; R7 : H, NH 2, mono-1-6C alkyl amino, di-1-6C alkylamino, 1-6C alkyl-CONH-, 1-6C alkyl-NHCONH-, 1-6C alkyl-O-CO-NH-, 1-6C alkyl, 1-6C alkoxy, NO 2or halo; R8 : H, NH 2, mono-1-6C alkylamino, di-1-6C alkylamino, 1-6C alkoxy or halo; and R9 : H or NH 2. [Image] [Image] ACTIVITY : Immunosuppressive; Cytostatic; Antiarthritic; Antirheumatic; Litholytic; Antibacterial; Osteopathic; Neuroprotective; Anti-HIV; Virucide; Antidiabetic; Antiinflammatory; Vasotropic; Endocrine-Gen.; Antipsoriatic; Antiarteriosclerotic; Immunomodulator; Nootropic; Cerebroprotective; Antiulcer; Gastrointestinal-Gen.; Cardiovascular-Gen.; Cardiant; Respiratory-Gen.; Hepatotropic; CNS-Gen.; Dermatological. MECHANISM OF ACTION : Interleukin-1beta inhibitor; Tumor necrosis factor-alpha inhibitor; Interleukin-1beta regulator; Tumor necrosis factor-alpha regulator. The ability of (I) to inhibit interleukin-1beta was tested using biological assays. The results showed that (I) exhibited an IC 50value of 1.8 mu M.