SULFONE SUBSTITUTED QUINAZOLINE DERIVATIVES AS IMMUNE-MODULATORS FOR THE TREATMENT OF INFLAMMATORY AND ALLERGIC DISEASES

摘要

Sulfone substituted quinazoline derivatives (I) and their salts, diastereomers and enantiomers, are new. Sulfone substituted quinazoline derivatives of formula (I) and their salts, diastereomers and enantiomers, are new. Either R 1>(hetero)aryl rings, 1-6C-alkyl, 2-6C-alkenyl, 2-6-alkynyl, 3-8C-cycloalkyl, or heterocyclyl ring with 3-8 ring atoms (all optionally substituted with one or more OH, NR 6>R 7>, NR 5>-C(O)-R 1> 0>, NR 5>-C(O)-OR 1> 0>, NR 5>-C(O)-NR 6>R 7>, NR 6>-SO 2-R 1> 0>, CN, halo, 1-6C-alkoxy, OCF 3, CF 3, 1-6C-alkyl, 3-6C-cycloalkyl and/or heterocyclyl with 3-8 ring atoms); and R 4>1-6C-alkyl, 3-8C-cycloalkyl or aryl ring, heterocyclyl ring with 3-8 ring atoms or heteroaryl ring (all optionally substituted OH, NR 8>R 9>, CN, halo, CF 3, 1-6C-alkoxy and/or OCF 3), C(O)-(1-6C)-alkyl, -C(O)-phenyl, -C(O)-benzyl or H; or XR 1>R 4>3-8 membered ring (which: optionally contains one or more heteroatoms, in addition to N, is optionally substituted by one or more OH, 1-6C-alkyl, 1-6C-alkoxy, C(O)R 1> 0>, SO 2R 1> 0>, halo or NR 7>R 8>, optionally contains 1-3 double bonds and/or is optionally interrupted by one or more -C(O)-group), when X is NR 4>; R 2>1-6C-alkyl or 1-6C-alkoxy (optionally substituted by halo, OH, 1-6C-alkoxy, CF 3, OCF 3 or NR 6>R 7>), H, OH, halo, CN, nitro, CF 3, OCF 3, C(O)OR 1> 0>, C(O)OH, C(O)NR 6>R 7>, C(S)NR 6>R 7>, NR 6>T 7>, NR 5>-C(O)-R 1> 0>, NR 5>-C(O)-OR 1> 0>, NR 5>-C(O)-NR 6>R 7>, NR 5>-SO 2-R 1> 0>, or 3-8C-cycloalkyl ring (optionally substituted by halo, OH, 1-6C-alkoxy, CF 3, OCF 3, NR 6>R 7> and/or 1-6C-alkyl); R 3>1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-7C-cycloalkyl or aryl ring, heterocyclyl ring with 3-8 ring atoms or a monocyclic heteroaryl ring (all optionally substituted by OH, -C(O)OR 1> 0>, -C(O)NR 6>R 7>, -NR 6>R 7>, CN, halo, CF 3, 1-6C-alkoxy, OCF 3 and/or 1-6C-alkyl ); X, Y 1>O or NR 4>; A : (hetero)aryl rings (optionally substituted with one or more OH, NR 6>R 7>, NR 5>-C(O)-R 1> 0>, C(O)NR 6>R 7>, NR 5>-C(O)-OR 1> 0>, NR 5>-C(O)-NR 6>R 7>, NR 6>-SO 2-R 1> 0>, CN, halo, 1-6C-alkoxy, OCF 3, CF 3, 1-6C-alkyl, 3-6C-cycloalkyl and/or heterocyclyl with 3-8 ring atoms); n : 1-6; R 5>H or 1-6C-alkyl; either R 6>, R 7>1-6C-alkyl, 2-6C-alkenyl, 3-8C-cycloalkyl- and/or aryl ring, heterocyclyl ring with 3-8 ring atoms and/or heteroaryl ring (all optionally substituted by one or more OH, NR 8>R 9>, CN, halo, CF 3, 1-6C-alkoxy and/or OCF 3) or H; R 6>R 7>N : 5-7-membered ring (which: optionally contains 1 or 2 further heteroatoms, in addition to N, and is optionally substituted by one or more OH, NR 8>R 9>, CN, halo, CF 3, 1-6C-alkyl, 1-6C-alkoxy and/or OCF 3); R 8>, R 9>H or 1-6C-alkyl (which is optionally substituted by OH or halo); and R 1> 0>1-6C-alkyl, 2-6C-alkenyl or 2-6C-alkynyl, 3-8C-cycloalkyl- or aryl- ring, heterocyclyl ring with 3-8 ring atoms or heteroaryl ring (optionally substituted by one or more OH, halo, CN, nitro, NR 6>R 7>, 1-6C-alkyl, CF 3, 1-6C-alkoxy and/or OCF 3). Independent claims are included for: (1) the preparations of (I); and (2) a benzonitrile compound of formula (II). [Image] [Image] - ACTIVITY : Antiinflammatory; Antiallergic; Cytostatic; Respiratory-Gen.; Antiasthmatic; Antibacterial; Immunosuppressive; Antipyretic; Antirheumatic; Antiarthritic; Vasotropic; Dermatological; Muscular-Gen.; Insecticide; Antipsoriatic; Antipruritic; Endocrine-Gen.; Nephrotropic; Hepatotropic; Virucide; Gastrointestinal-Gen.; Antiulcer; Ophthalmological; Cerebroprotective; Neuroprotective; Nootropic; Antianemic; Antithyroid; Antidiabetic; Immunomodulator. - MECHANISM OF ACTION : None given.