Patent EP-2072502-A1 (EP)
Inventor: SCHMEES NORBERT
IPC: A61K31/517
Filed: 2007-12-20
Abstract: Quinoline compounds (I) and/or their derivatives, nitrogen oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers or salts, are new. Quinoline compounds of formula (I) and/or their derivatives, nitrogen oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers or salts, are new. W 1>CH or N; Y 1>NR 1>R 2>or OR 1>; either R 1>, R 2>H, 1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 3-12C-heterocycloalkyl, 6-12C-aryl, 5-18C-heteroaryl, 1-6C-alkyl-1-6C-alkoxy, 1-6C-alkyl-1-6C- alkoxy-1-6C-alkoxy (all are unsubstituted or 1 or 2 times substituted by OH, halo, NO 2, CN, -NR 5>R 6>, C(O)NR 5>R, -S(O) 2NR 5>R 6>, NR 5>S(O) 2R 6>, NR 5>C(O)R 6>, SR 5>, R 5>, or OR 5>, where the carbon skeleton of the 3-10C-cycloalkyl and 1-10C-alkyl are optionally contains one or more N, O, S, NR 4>, C=O-group or one or more double bonds), (CH 2) n-6-12C-aryl, (CH 2) n-5-18C-heteroaryl, (CH 2) n-3-10C-cycloalkyl, (CH 2) n-3-12C-heterocycloalkyl, phenylene-(CH 2) p-R 6>, (CH 2) pPO 3(R 6>) 2, (CH 2) p-NR 4>C(=S)R 5>, (CH 2) p-NR 4>S(=O)R 5>, (CH 2) p-NR 4>C(=O)NR 5>R 6>-(CH 2) p-NR 4>C(=O)OR 5>,-(CH 2) p-NR 4>C(=NH)NR 5>R 6>, (CH 2) p-NR 4>C(=S)NR 5>R 6>, (CH 2) p-NR 4>S(=O)NR 5>R 6>, (CH 2) p-NR 4>S(=O) 2NR 5>R 6>, (CH 2) p-C(=O)R 5>, (CH 2) p-C(=S)R 5>, (CH 2) p-S(=O)R 5>, (CH 2) p-S(O)(NH)R 5>, (CH 2) p-S(O) 2R 5>, (CH 2) p-SO 2OR 5>, (CH 2) p-CO 2R 5>, (CH 2) p-CSNR 5>R 6>, CHR 5>R 6>, or (CH 2) p-SR 5>; or R 1>R 2>a bridge of 3-10 methylene units, where up to two methyl units are substituted by O, S or -NR 4>, and the phenyl is optionally one or more times substituted by OH, halo, NO 2, CN, phenyl, NR 5>R 6>, alkyl or OR 5>; T : 1-10C-alkyl, 2-10C-alkenyl, 2-10C-alkynyl, 1-6C-alkoxy, 3-10C-cycloalkyl, 3-12C-heterocycloalkyl, 6-12C-aryl or 5-18C-heteroaryl (all are optionally unsubstituted or one or more times substituted by OH, halo, NO 2, CN, phenyl, C(=O)R 5>, C(=O)OR 5>, C(=O)NR 5>R 6>, NR 5>R 6>, alkyl, -SR 5>or OR 5>); either R 3>T, H C(=O)R 5>, C(=O)NR 5>R 6>or C(=O)OR 5>; and R 4>T; or R 3>R 4>N, R 3>R 4>S : 5-10-membered ring consisting of C, N, O or S; either R 5>, R 6>1-10C-alkyl, 2-10C-alkenyl, 2-10C-alkynyl, 1-6C-alkoxy, 3-10C-cycloalkyl, 3-12C-heterocycloalkyl, 6-12C-aryl or 5-18C-heteroaryl (all are optionally substituted by OH, H, CN, NO 2, -OR 7>, NR 7>R 8>, C(O)NR 7>R 8>, -C(O)OR 7>or 1-6C-alkyl (which is unsubstituted, or one or more times substituted by halo, OH, CN, -NR 7>R 8>, -OR 7>or phenyl)). or H; or R 5>R 6>a bridge of 3-10 methylene units, where up to two methyl units are substituted by O, S or NR 4>; either R 7>, R 8>1-4C-alkyl, 5-18C-aryl or 5-18C-heteroaryl (all unsubstituted or one or more times substituted by halo or alkoxy), or H; or R 7>R 8>a bridge of 3-10 methylene units, where up to two methyl units are substituted by O, S or NR 4>; n : 1-6; and p : 0-6. When: Y 1>is NR 1>R 2>, and R 2>is hydrogen, then R 1>is not hydrogen; and Y 1>is OR 1>, then R 1>is not hydrogen. Independent claims are included for: (1) the preparation of (I); and (2) a quinoline intermediate compound of formula (II). X : halo, -OS(=O) 2R 9>-, OS(=O) 2C xF 2x+1, OP(=O)(OR 9>) 2or (NR 9>R 10>R 11>) +>.Z; R 9>-R 11>1-6C-alkyl or 6-12C-aryl; Z ->an anion, preferably a halide; and x : 1-5. [Image] [Image] ACTIVITY : Vasotropic; Cytostatic; Neuroprotective; Antiarteriosclerotic; Antiinflammatory; Antiarthritic; Antirheumatic; Antipsoriatic; Dermatological; Anticonvulsant; Nootropic; Antiparkinsonian; Anti-HIV. MECHANISM OF ACTION : Erythropoietin-producing hepatoma amplified sequence-receptor kinase inhibitor. The ability of (I) to inhibit erythropoietin-producing hepatoma amplified sequence-receptor kinase was tested in Chinese hamster ovary-erythropoietin-producing hepatoma amplified sequence B4 (CHO-EphB4) cells. The results showed that (I) exhibited an IC 5 0value of less than 10 mu M.