Patent DE-10214412-A1 (DE)
Inventor: HIMMELSBACH FRANK
IPC: C07D401/12
Filed: 2002-03-30
Abstract: 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).