| 摘要 |
6-(Hetero)cycloalkoxy-4-(N-(phenyl or 1-phenylethyl)-amino)-quinazoline or quinoline derivatives (I) are new. Bicyclic heterocycles of formula (I) and their tautomers, stereoisomers, isomer mixtures and salts are new. R1 = H or T; T = 1-4C alkyl; Rb = Ph' or CHMePh'; Ph' = phenyl substituted by R1 - R3; R1, R2 = H, halo, T, OH, OT, 2-3C alkenyl, 2-3C alkynyl, Ar, OAr, CH2Ar, OCH2Ar, Het, OHet, CH2Het, OCH2Het, CH2F, CHF2, CF3, OCH2F, OCHF2, OCF3, CN, NO2 or NH2; R3 = H, F, Cl, Br, Me or CF3; Rc = (i) 4-6C cycloalkyl, substituted by NR4R5 or by R6, (ii) azetidinyl-3-yl, pyrrolidin-3-yl or piperidin-(3 or 4)-yl, all substituted in the 1-position by R5; or (iii) tetrahydrofuran-3-yl or tetrahydropyran-(3 or 4)-yl; R4 = H or alkyl; R5 = H or alkyl (optionally monosubstituted by -CO-Q1); 2-4C alkyl monosubstituted by Q2; SO2T (optionally monosubstituted by Q3); COOT; COQ4; CN; or SO2Q1; Q1 = NH2, mono- or dialkylamino, pyrrolidino, piperidino, homopiperidino, morpholino, homomorpholino, piperazino, N-alkyl-piperazino, homopiperazino or N-alkyl-homopiperazino; Q2 = OH, alkoxy, NHCOOT, NH2, mono- or dialkylamino, NHCONH2, mono- or dialkylaminocarbonylamino, pyrrolidinocarbonylamino, piperidinocarbonylamino, morpholinocarbonylamino, alkylsulfonyl, alkylsulfonylamino or R6; Q3 = Cl, Br or as for Q1; Q4 = H, T, alkoxy-(1-4C) alkyl, tetrahydrofuranyl, tetrahydropyranyl, -T-Q1, alkylsulfonyl-(1-4C) alkyl, Q1, (alkoxy-(2-4C) alkyl)-amino, N-alkyl-N-(alkoxy-(2-4C) alkyl)-amino, -NH-Ar, 2-oxa-5-aza-bicyclo (2.2.1) hept-5-yl, 3-oxa-8-aza-bicyclo (3.2.1) oct-8-yl or 8-oxa-3-aza-bicyclo (3.2.1) oct-3-yl; R6 = 2-oxo-pyrrolidino, 2-oxo-piperidino, 3-oxo-morpholino, 2-oxo-imidazolidino, 3-alkyl-2-oxo-imidazolidino, 2-oxo-hexahydropyrimidino or 3-alkyl-2-oxo-hexahydropyrimidino; Rd = H, F, Cl, Br, OH, OT, OCH2F, OCHF2, OCF3 or mono- to pentafluoroethoxy; 2-4C alkoxy substituted by R6 or R7; tetrahydrofuran-3-yl, tetrahydropyran-(3 or 4)-yl, tetrahydrofuranyl-(1-4C) akyl or tetrahydropyranyl-(1-4C) alkyl; or OT, substituted by pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl (all optionally N-substituted by alkyl); R7 = OH, alkoxy, N(CH2CH2OMe)2, Q1, 2-oxa-5-aza-bicyclo (2.2.1) hept-5-yl, 3-oxa-8-aza-bicyclo (3.2.1) oct-8-yl or 8-oxa-3-aza-bicyclo (3.2.1) oct-3-yl, NHCHO, NHCOT, alkoxyalkylcarbonylamino, NHCOOT, NHCONH2, mono- or dialkylaminocarbonylamino, pyrrolidinocarbonylamino, piperidinocarbonylamino, morpholinocarbonylamino or alkylsulfonylamino; X = C-CN or N; Ar = phenyl (optionally substituted by 1 or 2 groups R9); R9 = H, halo, alkyl, OH, alkoxy, CHF2, CF3, OCHF2, OCF3 or CN; Het = pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl (all optionally substituted by 1 or 2 groups R9); pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl moieties are optionally substituted by 1 or 2 alkyl; unless specified otherwise alkyl moieties have 1-3C; the compound 4-((3-chloro-4-fluorophenyl)-amino)-6-((S)-tetrahydrofuran-3-yloxy)-7-hydroxy-quinazoline is excluded. An Independent claim is included for the preparation of (I).
|
