Patent DE-102007024470-A1 (DE)
Title: New sulfoximine-substituted quinoline and/or quinazoline derivatives are erythropoietin-producing hepatoma amplified sequence-receptor kinase inhibitors useful to prepare medicaments to e.g. treat endometriosis and stenosis
Inventor: PRIEN OLAF
IPC: A61P25/00
Filed: 2007-05-24
Abstract: Sulfoximine-substituted quinoline and/or quinazoline derivatives (I) and their N-oxides, solvates, hydrates, stereoisomers, diastereoisomers, enantiomers and salts are new. Sulfoximine-substituted quinoline and/or quinazoline derivatives of formula (I) and their N-oxides, solvates, hydrates, stereoisomers, diastereoisomers, enantiomers and salts are new. W 1>CH or N; Y 1>-Q : NR 1>R 2> or OR 1>; either R 1>, R 2>H, OH, halo, nitro, CN, 1-6C alkyl, 1-4C hydroxyalkyl, -2-6C-alkenyl, -2-6C-alkynyl, -3-10C-cycloalkyl, -3-12C-heterocycloalkyl, -6-12C-aryl, -5-18C-heteroaryl, -1-6C-alkoxy, -1-6C-alkoxy-1-6C-alkoxy, -1-6C-alkoxy-1-6C-alkyl, -1-6C-alkoxy-1-6C-alkoxy-1-6C-alkyl, -(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 5>R 6>, -(CH 2) p-NR 4>COR 5>, -(CH 2) p-NR 4>CSR 5>, -(CH 2) p-NR 4>S(O)R 5>, -(CH 2) p-NR 4>S(O) 2R 5>, -(CH 2) p-NR 4>CONR 5>R 6>, -(CH 2) p-NR 4>COOR 5>, -(CH 2) p-NR 4>C(NH)NR 5>R 6>, -(CH 2) p-NR 4>CSNR 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-COR 5>, -(CH 2) p-CSR 5>, -(CH 2) p-S(O)R 5>, -(CH 2) p-S(O)(NH)R 5>, -(CH 2)-S(O) 2R 5>, -(CH 2) p-S(O) 2NR 5>R 6>, -(CH 2) p-SO 2OR 5>, -(CH 2) p-CO 2R 5>, -(CH 2) p-CONR 5>R 6>, -(CH 2) p-CSNR 5>R 6>, -OR 5>, -CHR 5>R 6>, -(CH 2) p-SR 5> or -CR 5>(OH)-R 6> (where: -1-6C-alkyl, -2-6C-alkenyl, -2-6-alkynyl, -3-10C-cycloalkyl, -3-12C-heterocycloalkyl, -6-12C-aryl, -5-18C-heteroaryl or -1-6C-alkoxy are optionally substituted with OH, halo, nitro, CN, -NR 5>R 6>, -C(O)NR 5>R 6>, -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>; and the carbon skeleton of -3-10C-cycloalkyl and -1-10C-alkyl contain N-, O-, S-atoms, -NR 4>, C=O-group or one or more double bond); or R 1>R 2>optionally forms bridge from 3-10 methylene units, where up to two methylene units are optionally replaced with O, S or -NR 4> and the phenyl-residue is optionally substituted with one or more OH, halo, nitro, CN, phenyl, -NR 5>R 6>, alkyl or -OR 5>; R 3>, R 4>H, -1-10C-alkyl, -2-6C-alkenyl, -2-6C-alkynyl, -3-10C-cycloalkyl, -3-12C-heterocycloalkyl or -1-10C-alkanoyl, where -1-10C-alkyl, -2-6C-alkenyl, -2-6C-alkynyl, -3-10C-cycloalkyl, -3-12C-heterocycloalkyl or -1-10C-alkanoyl are optionally substituted with one or more OH, halo, nitro, CN, phenyl, -NR 5>R 6>, alkyl, -SR 5> or -OR 5>; either R 5>, R 6>H, -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 (where -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 are optionally substituted with one or more OH, halo, CN, nitro, -OR 7>, -NR 7>R 8>, -C(O)NR 7>R 8>, -C(O)OR 7> or -1-6C-alkyl, and -1-6C-alkyl is optionally substituted with halo, OH, CN, -NR 7>R 8>, -OR 7> or phenyl); or R 5>R 6>optionally forms bridge from 3-10 methylene unit, where up to two methylene units are replaced with O, S or NR 4>; either R 7>, R 8>H, -1-4C-alkyl, -6-12C-aryl or -5-18C-heteroaryl, where alkyl, aryl and heteroaryl are optionally substituted with one or more halo or alkoxy; or R 7>R 8>optionally forms bridge from 3-10 methylene units, where up to two methylene units are replaced with O, S or -NR 4>; n : 1-6; and p : 0-6. An independent claim is included for the preparation of (I). [Image] ACTIVITY : Angiogenesis inhibitor; Cytostatic; Neuroprotective; Gynecological; Ophthalmological; Cardiant; Vasotropic; Antiarteriosclerotic; Antiinflammatory; Antiarthritic; Anticonvulsant; Nootropic; Antiparkinsonian. MECHANISM OF ACTION : Erythropoietin-producing hepatoma amplified sequence (Eph)-receptor kinase inhibitor; Tyrosine kinase receptor inhibitor. The ability of (I) to inhibit erythropoietin-producing hepatoma amplified sequence (Eph)-receptor kinase was tested in a recombinant EphB4 kinase. The results showed that IC 5 0 of (I) was 10 mu M.