Patent EP-2321284-B1 (EP)
Inventor: BUCHMANN BERND
IPC: A61K31/517
Filed: 2009-07-18
Granted: 2012-05-09
Abstract: 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.