Aminoquinazolines and their use as medicaments

A compound of the formula:

• wherein
• X denotes a nitrogen atom,
• Ra denotes a hydrogen atom or a methyl group,
• Rb denotes a phenyl, benzyl or 1-phenylethyl group, wherein the phenyl nucleus in each case is substituted by the groups R1 to R3, where
• R1 and R2, which may be identical or different, each denote a hydrogen, fluorine, chlorine, bromine or iodine atom,
• a methyl, ethyl, hydroxy, methoxy, ethoxy, amino, cyano, vinyl or ethynyl group,
• an aryl, aryloxy, arylmethyl or arylmethoxy group,
• a methyl or methoxy group substituted by 1 to 3 fluorine atoms or
• R1 together with R2, if they are bound to adjacent carbon atoms, denotes a —CH═CH—CH═CH, —CH═CH—NH or —CH═N—NH group and
• R3 denotes a hydrogen, fluorine, chlorine or bromine atom,
• one of the groups Rc or Rd denotes an —A—B group and
• the other group Rc or Rd denotes a —C—D group, where
• A denotes a C1-6-alkylene group, a —O—C1-6-alkylene group, where the alkylene moiety is linked to the group B, or an oxygen atom, with the proviso that if A is an oxygen atom it may not be linked to the group B via a nitrogen atom of the group B, and
• B denotes a pyrrolidino group wherein the two hydrogen atoms in the 2 position are replaced by a group E, wherein
• E represents a —CH2—O—CO—CH2, —CH2CH2—O—CO, —CH2—O—CO—CH2CH2, —CH2CH2—O—CO—CH2 or —CH2CH2CH2—O—CO— bridge optionally substituted by one or two C1-2-alkyl groups,
• a pyrrolidino group wherein the two hydrogen atoms in the 3 position are replaced by a group F wherein
• F denotes an —O—CO—CH2CH2, —CH2—O—CO—CH2, —CH2CH2—O—CO, —O—CO—CH2CH2CH2, —CH2—O—CO—CH2CH2, —CH2CH2—O—CO—CH2, —CH2CH2CH2—O—CO, —O—CO—CH2—NR4—CH2, —CH2—O—CO—CH2—NR4, —O—CO—CH2—O—CH2 or —CH2—O—CO—CH2—O— bridge optionally substituted by one or two C1-2-alkyl groups, where R4 denotes a hydrogen atom or a C1-4-alkyl group,
• a piperidino or hexahydroazepino group, wherein the two hydrogen atoms in the 2 position are replaced by a group E, where E is as hereinbefore defined,
• a piperidino or hexahydroazepino group, wherein in each case the two hydrogen atoms in the 3 position or in the 4 position are replaced by a group F, where F is as hereinbefore defined,
• a piperazino or 4-(C1-4-alkyl)-piperazino group, wherein the two hydrogen atoms in the 2 position or in the 3 position of the piperazino ring are replaced by a group E, where E is as hereinbefore defined,
• a pyrrolidino or piperidino group, wherein two neighbouring hydrogen atoms are replaced by a —O—CO—CH2, —CH2—O—CO, —O—CO—CH2CH2, —CH2—O—CO—CH2, —CH2CH2—O—CO, —O—CO—CH2—NR4 or —O—CO—CH2—O— bridge optionally substituted by one or two C1-2-alkyl groups, where
• R4 is as hereinbefore defined and the heteroatoms of the abovementioned bridges are not bound to the 2 or 5 position of the pyrrolidino ring and are not bound to the 2 or 6 position of the piperidino ring,
• a piperazino or 4-(C1-4-alkyl)-piperazino group, wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 3 position of the piperazino ring are replaced by a —CH2—O—CO—CH2 or —CH2CH2—O—CO— bridge optionally substituted by one or two C1-2-alkyl groups,
• a piperazino group wherein a hydrogen atom in the 3 position together with the hydrogen atom in the 4 position are replaced by a —CO—O—CH2CH2 or —CH2—O—CO—CH2— bridge optionally substituted by one or two C1-2-alkyl groups, where in each case the left-hand end of the abovementioned bridges is bound to the 3 position of the piperazino ring,
• a pyrrolidino, piperidino or hexahydroazepino group substituted by the group R5 wherein
• R5 represents a 2-oxo-tetrahydrofuranyl, 2-oxo-tetrahydropyranyl, 2-oxo-1,4-dioxanyl or 2-oxo-4-(C1-4-alkyl)-morpholinyl group optionally substituted by one or two C1-2-alkyl groups,
• a pyrrolidino group substituted in the 3 position by a 2-oxo-morpholino group, while the 2-oxo-morpholino group may be substituted by one or two C1-2-alkyl groups,
• a piperidino or hexahydroazepino group substituted in the 3 or 4 position by a 2-oxo-morpholino group, while the 2-oxo-morpholino group may be substituted by one or two C1-2-alkyl groups,
• a 4-(C1-4-alkyl)-piperazino or 4-(C1-4-alkyl)-homopiperazino group substituted at a cyclic carbon atom by R5, wherein R5 is as hereinbefore defined,
• a piperazino or homopiperazino group substituted in the 4 position by the group R6, wherein
• R6 represents a 2-oxo-tetrahydrofuran-3-yl, 2-oxo-tetrahydrofuran-4-yl, 2-oxo-tetrahydropyran-3-yl, 2-oxo-tetrahydropyran-4-yl or 2-oxo-tetrahydropyran-5-yl group optionally substituted by one or two C1-2-alkyl groups,
• a pyrrolidino group substituted in the 3 position by an (R4NR6), R6O, R6S, R6SO or R6SO2 group, where R4 and R6 are as hereinbefore defined,
• a piperidino or hexahydroazepino group substituted in the 3 or 4 position by an (R4NR6), R6O, R6S, R6SO or R6SO2 group, wherein R4 and R6 are as hereinbefore defined,
• a pyrrolidino, piperidino or hexahydroazepino group substituted by an R5—C1-4-alkyl, (R4NR6)—C1-4-alkyl, R6O—C1-4-alkyl, R6S—C1-4-alkyl, R6SO—C1-4-alkyl, R6SO2—C1-4-alkyl or R4NR6—CO group, wherein R4 to R6 are as hereinbefore defined,
• a pyrrolidino group substituted in the 3 position by an R5—CO—NR4, R5—C1-4-alkylene-CONR4, (R4NR6)—C1-4-alkylene-CONR4, R6O—C1-4-alkylene-CONR4, R6S—C1-4-alkylene-CONR4, R6SO—C1-4-alkylene-CONR4, R6SO2—C1-4-alkylene-CONR4, 2-oxo-morpholino-C1-4-alkylene-CONR4, R5—C1-4-alkylene-Y or C2-4-alkyl-Y group, where the C2-4-alkyl moiety of the C2-4-alkyl-Y group in each case is substituted from position 2 by an (R4NR6), R6O, R6S, R6SO or R6SO2 group and the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups, wherein
• R4 to R6 are as hereinbefore defined and
• Y represents an oxygen or sulphur atom, an imino, N—(C1-4-alkyl)-imino, sulphinyl or sulphonyl group,
• a piperidino or hexahydroazepino group substituted in the 3 or 4 position by an R5—CO—NR4, R5—C1-4-alkylene-CONR4, (R4NR6)—C1-4-alkylene-CONR4, R6O—C1-4-alkylene-CONR4, R6S—C1-4-alkylene-CONR4, R6SO—C1-4-alkylene-CONR4, R6SO2—C1-4-alkylene-CONR4, 2-oxo-morpholino-C1-4-alkylene-CONR4, R5—C1-4-alkylene-Y or C2-4-alkyl-Y group, wherein
• Y is as hereinbefore defined, the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups and the C2-4-alkyl moiety of the C2-4-alkyl-Y group is substituted in each case from position 2 by an (R4NR6), R6O, R6S, R6SO or R6SO2 group, where R4 to R6 are as hereinbefore defined,
• a 4-(C1-4-alkyl)-piperazino or 4-(C1-4-alkyl)-homopiperazino group substituted at a cyclic carbon atom by an R5—C1-4-alkyl, (R4NR6)—C1-4-alkyl, R6O—C1-4-alkyl, R6S—C1-4-alkyl, R6SO—C1-4-alkyl, R6SO2—C1-4-alkyl or R4NR6—CO group, wherein R4 to R6 are as hereinbefore defined,
• a piperazino or homopiperazino group substituted in the 4 position by an R5—C1-4-alkyl, R5—CO, R5—C1-4-alkylene-CO, (R4NR6)—C1-4-alkylene-CO, R6O—C1-4-alkylene-CO, R6S—C1-4-alkylene-CO, R6SO—C1-4-alkylene-CO or R6SO2—C1-4-alkylene-CO group, wherein R4 to R6 are as hereinbefore defined,
• a piperazino or homopiperazino group substituted in the 4 position by a C2-4-alkyl group, wherein the C2-4-alkyl group is substituted in each case from position 2 by an (R4NR6), R6O, R6S, R6SO or R6SO2 group, where R4 and R6 are as hereinbefore defined,
• a pyrrolidino. piperidino or hexahydroazepino group substituted by a 2-oxo-morpholino-C1-4-alkyl group, wherein the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups,
• a pyrrolidino group substituted in the 3 position by a C2-4-alkyl-Y group, wherein
• Y is as hereinbefore defined and the C2-4-alkyl moiety of the C2-4-alkyl-Y group is substituted in each case from position 2 by a 2-oxo-morpholino group optionally substituted by one or two C1-2-alkyl groups,
• a piperidino or hexahydroazepino group substituted in the 3 or 4 position by a C2-4-alkyl-Y group, wherein
• Y is as hereinbefore defined and the C2-4-alkyl moiety of the C2-4-alkyl-Y group is substituted in each case from position 2 by a 2-oxo-morpholino group optionally substituted by one or two C1-2-alkyl groups,
• a 4-(C1-4-alkyl)-piperazino or 4-(C1-4-alkyl)-homopiperazino group substituted at a cyclic carbon atom by a 2-oxo-morpholino-C1-4-alkyl group, wherein the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups,
• a piperazino or homopiperazino group substituted in the 4 position by a 2-oxo-morpholino-C1-4-alkylene-CO group, wherein the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups,
• a piperazino or homopiperazino group substituted in the 4 position by a C2-4-alkyl group, wherein the C2-4-alkyl moiety is substituted in each case from position 2 by a 2-oxo-morpholino group optionally substituted by one or two C1-2-alkyl groups,
• a pyrrolidinyl or piperidinyl group substituted in the 1 position by the group R6, by an R5—C1-4-alkyl, R5—CO, R5—C1-4-alkylene-CO, (R4NR6)—C1-4-alkylene-CO, R6O—C1-4-alkylene R6S—C1-4-alkylene-CO, R6SO—C1-4-alkylene-CO, R6SO2—C1-4-alkylene-CO or 2-oxo-morpholino-C1-4-alkylene-CO group, wherein
• R4 to R6 are as hereinbefore defined and the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups,
• a pyrrolidinyl or piperidinyl group substituted in the 1 position by a C2-4-alkyl group, wherein the C2-4-alkyl moiety is substituted in each case from position 2 by an (R4NR6), R6O, R6S, R6SO, R6SO2 or 2-oxo-morpholino group, where
• R4 and R6 are as hereinbefore defined and the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups,
• a pyrrolidin-3-yl-NR4, piperidin-3-yl-NR4 or piperidin-4-yl-NR4 group substituted in each case at the cyclic nitrogen atom by the group R6, by an R5—C1-4-alkyl, R5—CO, R5—C1-4-alkylene-CO, (R4NR6)—C1-4-alkylene-CO, R6O—C1-4-alkylene-CO, R6S—C1-4-alkylene-CO, R6SO—C1-4-alkylene-CO, R6SO2—C1-4-alkylene-CO or 2-oxo-morpholino-C1-4-alkylene-CO group, wherein
• R4 to R6 are as hereinbefore defined and the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups,
• a pyrrolidin-3-yl-NR4, piperidin-3-yl-NR4 or piperidin-4-yl-NR4 group substituted in each case at the cyclic nitrogen atom by a C2-4-alkyl group, wherein the C2-4-alkyl moiety is substituted in each case from position 2 by an (R4NR6), R6O, R6S, R6SO, R6SO2 or 2-oxo-morpholino group, where
• R4 and R6 are as hereinbefore defined and the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups,
• a R5—C1-4-alkylene-NR4 group wherein R4 and R5 are as hereinbefore defined, or
• a C2-4-alkyl-NR4 group wherein the C2-4-alkyl moiety is substituted in each case from position 2 by an (R4NR6), R6O, R6S, R6SO, R6SO2 or 2-oxo-morpholino group, where
• R4 and R6 are as hereinbefore defined and the 2-oxo-morpholino moiety may be substituted by one or two C1-2-alkyl groups,
• a 2-oxo-morpholin-4-yl group substituted by the group R7 or by the group R7 and a C1-4-alkyl group,
• where
• R7 represents a C3-4-alkyl, hydroxy-C1-4-alkyl, C1-4-alkoxy-C1-4-alkyl, di-(C1-4-alkyl)-amino-C1-4-alkyl, pyrrolidino-C1-4-alkyl, piperidino-C1-4-alkyl, morpholino-C1-4-alkyl, 4-(C1-4-alkyl)-piperazino-C1-4-alkyl, C1-4-alkylsulphanyl-C1-4-alkyl, C1-4-alkylsulphinyl-C1-4-alkyl, C1-4-alkyl-sulphonyl-C1-4-alkyl, cyano-C1-4-alkyl, C1-4-alkoxycarbonyl-C1-4-alkyl, aminocarbonyl-C1-4-alkyl, C1-4-alkyl-aminocarbonyl-C1-4-alkyl, di-(C1-4-alkyl)-aminocarbonyl-C1-4-alkyl, pyrrolidinocarbonyl-C1-4-alkyl, piperidinocarbonyl-C1-4-alkyl, morpholinocarbonyl-C1-4-alkyl or a 4-(C1-4-alkyl)-piperazinocarbonyl-C1-4-alkyl group,
• a 2-oxo-morpholin-4-yl group substituted by two groups R7, where R7 is as hereinbefore defined and the two groups R7 may be identical or different,
• a 2-oxo-morpholin-4-yl group wherein the two hydrogen atoms of a methylene group are replaced by a —(CH2)m, —CH2—Y—CH2, —CH2—Y—CH2—CH2, —CH2CH2—Y—CH2CH2 or —CH2CH2—Y—CH2CH2CH2— bridge optionally substituted by one or two C1-2-alkyl groups, where
• Y is as hereinbefore defined and m represents the number 2, 3, 4, 5 or 6,
• a 2-oxo-morpholin-4-yl group wherein a hydrogen atom in the 5 position together with a hydrogen atom in the 6 position is replaced by a —(CH2)n, —CH2—Y—CH2, —CH2—Y—CH2CH2 or —CH2—CH2—Y—CH2— bridge, where
• Y is as hereinbefore defined and
• n denotes the number 2, 3 or 4,
• or, if C together with D represents a group Rc, it may also represent a 2-oxo-morpholin-4-yl group which may be substituted by 1 to 4 C1-2-alkyl groups,
• C denotes an —O—C1-6-alkylene group, where the alkylene moiety is linked to the group D, or an oxygen atom, while this may not be linked to a nitrogen atom of the group D, and
• D denotes an amino group substituted by 2 C1-4-alkyl groups wherein the alkyl groups may be identical or different and each alkyl moiety may be substituted from position 2 by a C1-4-alkoxy or di-(C1-4-alkyl)-amino group or by a 4- to 7-membered alkyleneimino group, while in the abovementioned 6- or 7-membered alkyleneimino groups a methylene group in each case may be replaced in the 4 position by an oxygen or sulphur atom of by a sulphinyl, sulphonyl or N—(C1-4alkyl)-imino group,
• a 4- or 7-membered alkyleneimino group optionally substituted by 1 to 4 methyl group,
• a 6- to 7-membered alkyleneimino group optionally substituted by 1 to 2 methyl group where in each case a methylene group in the 4 position is replaced by an oxygen of sulphur atom, by a sulphinyl, sulphonyl, or N—(C1-4-alkyl)-imino group,
• an imidazolyl group optionally substituted by 1 to 3 methyl group,
• a C5-7-cycloalkyl group wherein a methylene group is replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl or N—(C1-4-alkyl)-imino group, or
• C together with D denotes a hydrogen atom,
• a C1-6-alkoxy group optionally substituted from position 2 by a hydroxy or C1-4-alkyl group,
• a C3-7-cycloalkoxy or C3-7-cycloalkyl-C1-4-alkoxy group,
• a tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4-yloxy, tetrahydrofuranylmethoxy or tetrahydropyranylmethoxy group,
• or a group Rc, where
• Rc denotes a C2-6-alkoxy group which is substituted from position 2 by a C4-7-cycloalkoxy or C3-7-cycloalkyl-C1-3-alkoxy group,
• a C4-7-cycloalkoxy or C3-7-cycloalkyl-C1-6-alkoxy group, wherein the cycloalkyl moiety is substituted in each case by a C1-4-alkyl, C1-4-alkoxy, di-(C1-4-alkyl)-amino, pyrrolidino, piperidino, morpholino, piperazino, N—(C1-2-alkyl)-piperazino, C1-4-alkoxy-C1-2-alkyl, di-(C1-4-alkyl)-amino-C1-2-alkyl, pyrrolidino-C1-2-alkyl, piperidino-C1-2-alkyl, morpholino-C1-2-alkyl, piperazino-C1-2-alkyl or N—(C1-2-alkyl)-piperazino-C1-2-alkyl group, where the abovementioned cycloalkyl moieties may additionally be substituted by a methyl or ethyl group,
• while, unless stated otherwise, the aryl moieties mentioned in the definition of the abovementioned groups denote a phenyl group which may be mono- or disubstituted by R′, while the substituents may be identical or different, and
• R′ represents a fluorine, chlorine, bromine or iodine atom, a C1-2-alkyl, trifluoromethyl or C1-2-alkoxy group, or wherein if a phenyl group is disubstituted by R′ and the
• two groups R′ are bound to adjacent carbon atoms of the phenyl group then the two groups R′ may together denote a C3-4-alkylene, methylenedioxy or 1,3-butadien-1,4-ylene group,
• or a tautomer or salt thereof.