Patent DE-19928281-A1 (DE)
Title: Arylamino and aralkylamino substituted quinoline and quinazoline derivatives, useful for the treatment of e.g. tumors, pulmonary, respiratory and gastrointestinal disorders and psoriasis
Inventor: HIMMELSBACH FRANK
IPC: C07D239/94
Filed: 1999-06-21
Abstract: Substituted amino-quinoline and amino-quinazoline derivatives are new.  Substituted amino-quinoline and amino-quinazoline derivatives of formula (I) and their tautomers, stereoisomers and salts are new. Ra = H or 1-4C alkyl; Rb = Ph, Ph-CH2-, or -CH(Ph)-CH3-;  Ph = phenyl substituted by R1-R3; R1, R2 = H, halo, 1-4C alkyl, OH, 1-4C alkoxy, 3-6C cycloalkyl, 4-6C cycloalkoxy, 2-5C alkenyl, 2-5C alkynyl, Ar, Ar-O-, Ar-CH2-, Ar-O-CH2-, 3-5C alkenyloxy, 3-5C alkynyloxy, 1-4C alkylthio, 1-4C alkyl-SO-, 1-4C alkyl-SO2-, CF3-S-, CF3-SO-, CF3-SO2-, CH3 or OCH3 substituted with 1-3 F, C2H5 or OCH2H5 substituted by 1-5 F, CN, NO2, NH2, (1-4C alkyl)NH-, or (1-4C alkyl)2N-; or  R1 + R2 on adjacent C atoms = -CH = CH-CH=CH-, -CH=CH-NH- or -CH=N-NH-; R3 = H, F, Cl, Br, 1-4C alkyl, CF3, or 1-4C alkoxy; X = C(CN) or N; A = imino optionally substituted by 1-4C alkyl; B = C(O) or SO2; C = 1,3-allenylene, 1,1-vinylene or 1,2-vinylene (all optionally substituted by CF3 or 1-2 CH3), ethynylene, or 1,3-butadien-1,4-ylene optionally substituted by CF3 or 1-4 CH3; D = 1-8C alkylene, -CO-1-8C alkylene or -SO2-1-8C alkylene (optionally substituted by 1-4F), -CO-O-1-8C alkylene, -CO-NR4-1-8C alkylene, or -SO2-NR4-1-8C alkylene; or D = bond when attached to a C atom of E or CO or SO2 when attached to a N atom of E; E = NH2, or (1-4C alkyl)NH-, (1-4C alkyl)2N-, (2-4C alkyl)NH-, (1-4C alkyl)(2-4C alkyl)N- or (2-4C alkyl)2N- (all substituted in the beta -,  psi - or  delta -position by R5), (3-7C cycloalkyl)NH- or (3-7C cycloalkyl-1-3C alkyl)NH- (all optionally N-substituted by 1-4C alkyl), NH2 or (1-4C alkyl)NH- (all optionally N-substituted by tetrahydrofuran-3-yl, tetrahydropyran-(3 or 4)-yl, tetrahydrofuranylmethyl, 1-(tetrahydrofuran-3-yl)-piperidin-4-yl, 1-(tetrahydropyran-(3 or 4)-yl)-piperidin-4-yl, 3-pyrrolidinyl, 3- or 4-piperidinyl or 3- or 4-hexahydroazepinyl (all optionally substituted by 1-3 1-4C alkyl)), 4-7 membered alkyleneimino (optionally substituted by 1-4 CH3 or C2H5, and optionally substituted on a ring C atom or CH3 or C2H5 substituent by R5), piperidino (substituted by tetrahydrofuranyl, tetrahydropyranyl or tetrahydrofuranylmethyl), 6-7 membered alkyleneimino (optionally substituted with 1-2 CH3 or C2H5 and containing O, S, NR6, SO or SO2 in place of CH2 in the 4-position), imidazolyl (optionally substituted by 1-3 CH3), or 5-7C cycloalkyl containing O, S NR6, SO OR SO2 in place of 1 CH2; or D + E = H, F, Cl, 1-4C alkyl (optionally substituted by 1-5 F), 3-6C cycloalkyl, Ar, Het, 1-4C alkylcarbonyl, Ar-CO-, COOH, 1-4C alkoxycarbonyl, -CONH2, -CONH(1-4C alkyl), -CON(1-4C alkyl)2, or C(O) substituted with 4-7 membered alkyleneimino optionally containing O, S NR6, SO or SO2 in place of CH2 in the 4-position when it is 6-7 membered; Rc = 4-7C cycloalkoxy or 3-7C cycloalkoxy-1-6C alkoxy (each optionally ring-substituted with 1-3C alkyl, OH, 1-4C alkoxy, NH2, (1-4C alkyl)NH-, (1-4C alkyl)2N-, pyrrolidino, piperidino, morpholino, piperazino, N-(CH3 or C2H5)-piperazino, CH3 or C2H5 (all substituted by OH, 1-4C alkoxy, NH2, (1-4C alkyl)NH-, (1-4C alkyl)2N-, pyrrolidino, piperidino, morpholino, piperazino, N-(CH3 or C2H5)-piperazino, and the monosubstituted cycloalkyl group is optionally substituted by 1-3C alkyl), tetrahydrofuran-3-yloxy, tetrahydropyran-(3 or 4)-yloxy, tetrahydrofuranylmethoxy, 2-4C alkoxy (substituted in the  beta -, psi - or  delta -position by azetidin-1-yl or 4-(CH3 or C2H5)-homopiperazino), or 3-pyrrolidinyloxy, 2- or 3-pyrrolidinyl-1-4C alkoxy, 3- or 4-piperidinyloxy, 2-, 3- or 4-piperidinyl-1-4C alkoxy, 3- or 4-hexahydro-azepinyloxy or 2-, 3- or 4-hexahydro-azepinyl-1-4C alkoxy (all N-substituted by R6); R4 = H or 1-4C alkyl; R5 = OH, 1-4C alkoxy, NH2, (1-4C alkyl)NH, (1-4C alkyl)2N-, 4-7 membered alkyleneimino (optionally substituted with 1-2 CH3 and optionally containing O, S, SO, SO2, NH or N(1-4C alkyl) in place of CH2 in the 4-position when it is 6-7 membered); R6 = H, 1-4C alkyl, -CH2-CH2-OCH3, -(CH2)3-OCH3, 3-7C cycloalkyl; 3-7C cycloalkyl-1-4C alkyl, tetrahydrofuran-3-yl, tetrahydropyran-(3 or 4)-yl, tetrahydrofuranylmethyl, CHO, 1-4C alkylcarbonyl, 1-4C alkyl-SO2-, -CONH2, -CONH(1-4C alkyl), or -CON(1-4C alkyl)2; Het = 5-membered heteroaryl containing NH, O or S and optionally 1-2 N, and optionally substituted by 1-2 CH3 or C2H5, or 6-membered heteroaryl containing 1-3 N and optionally substituted by 1-2 CH3 or C2H5 or by halo, CF3, OH, OCH3 or OC2H5; Ar = phenyl optionally substituted with R7 or 1-3 R8, or R7 and 1-2 R8; R7 = CN, COOH, 1-4C alkoxycarbonyl, -CONH2, -CONH(1-4C alkyl), -CON(1-4C alkyl)2, 1-4C alkylthio, 1-4C alkyl-SO-, 1-4C alkyl-SO2-, OH, 1-4C alkyl-SO2-O-, CF3O-, NO2, NH2, (1-4C alkyl)NH-, (1-4C alkyl)2N-, 1-4C alkylcarbonyl-NH -, (1-4C alkyl)(1-4C alkylcarbonyl)N-, 1-4C alkyl-SO2-NH-, 1-4C alkyl-SO2-N(1-4C alkyl)-, SO2-NH2, -SO2-NH(1-4C alkyl), -SO2-N(1-4C alkyl), or C(O) (substituted by 5-7 membered alkyleneimino optionally containing O, S, SO, SO2 NH or N(1-4C alkyl) in place of the CH2 in the 4-position when it is 6-7 membered); and R8 = halo, 1-4C alkyl, CF3, or 1-4C alkoxy; or 2R8 on adjacent C atoms = 3-5C alkylene, methylenedioxy or 1,3-butadien-1,4-ylene. An Independent claim is also included for the preparation of compounds (I).