Bicyclic Heterocycles, Pharmaceutical Compositions Containing These Compounds, Their Use and Processes for Preparing Them

Bicyclic heterocycles of general formula

• wherein
• Ra denotes a hydrogen atom or a C1-4-alkyl group,
• Rb denotes a phenyl, benzyl or 1-phenylethyl group wherein the phenyl nucleus is substituted in each case by the groups R1 to R3, whilst
• R1 and R2, which may be identical or different, in each case denote a hydrogen, fluorine, chlorine, bromine or iodine atom,
• a C1-4-alkyl, hydroxy, C1-4-alkoxy, C3-6-cycloalkyl, C4-6-cycloalkoxy, C2-5-alkenyl or
• C2-5-alkynyl group,
• an aryl, aryloxy, arylmethyl or arylmethoxy group,
• a C3-5-alkenyloxy or C3-5-alkynyloxy group, whilst the unsaturated moiety may not be linked to the oxygen atom,
• a C1-4-alkylsulfenyl, C1-4-alkylsulfinyl, C1-4-alkylsulfonyl, C1-4-alkylsulfonyloxy, trifluoromethylsulfenyl, trifluoromethylsulfinyl or trifluoromethylsulfonyl group,
• a methyl or methoxy group substituted by 1 to 3 fluorine atoms,
• an ethyl or ethoxy group substituted by 1 to 5 fluorine atoms,
• a cyano or nitro group or an amino group optionally substituted by one or two C1-4-alkyl groups, wherein the substitutents may be identical or different, or
• R1 together with R2, if they are bound to adjacent carbon atoms, denote a —
• CH═CH—CH═CH, —CH═CH—NH or —CH═N—NH group and
• R3 denotes a hydrogen, fluorine, chlorine or bromine atom,
• a C1-4-alkyl, trifluoromethyl or C1-4-alkoxy group,
• X denotes a methine group substituted by a cyano group or a nitrogen atom,
• A denotes an imino group optionally substituted by a C1-4-alkyl group,
• B denotes a carbonyl or sulfonyl group,
• C denotes a 1,3-allenylene, 1,1- or 1,2-vinylene group which may be substituted in each case by one or two methyl groups or by a trifluoromethyl group,
• an ethynylene group or
• a 1,3-butadien-1,4-ylene group optionally substituted by 1 to 4 methyl groups or by a trifluoromethyl group,
• D denotes an alkylene, —CO-alkylene or —SO2-alkylene group wherein the alkylene moiety in each case contains 1 to 8 carbon atoms and additionally 1 to 4 hydrogen atoms in the alkylene moiety may be replaced by fluorine atoms, whilst the linking of the —CO-alkylene or —SO2-alkylene group to the adjacent group C in each case must take place via the carbonyl or sulfonyl group,
• a —CO—O-alkylene, —CO—NR4-alkylene or —SO2—NR4-alkylene group wherein the alkylene moiety in each case contains 1 to 8 carbon atoms, whilst the linking to the adjacent group C in each case must take place via the carbonyl or sulfonyl group, wherein
• R4 denotes a hydrogen atom or a C1-4-alkyl group,
• or, if D is bound to a carbon atom of the group E, it may also denote a bond
• or, if D is bound to a nitrogen atom of the group E, it may also denote a carbonyl or sulfonyl group,
• E denotes an amino, C1-4-alkylamino or di-(C1-4-alkyl)-amino group wherein the alkyl moieties may be identical or different,
• a C2-4-alkylamino group wherein the alkyl moiety is substituted in β-, γ-, or δ-position with regard to the nitrogen atom of the amino group by the group R5, whilst
• R5 denotes a hydroxy, C1-4-alkoxy, amino, C1-4-alkylamino or di-(C1-4-alkyl)-amino group,
• a 4- to 7-membered alkyleneimino group optionally substituted by one or two methyl groups or
• a 6- to 7-membered alkyleneimino group optionally substituted by one or two methyl groups wherein in each case a methylene group in position 4 is replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, imino or N—(C1-4-alkyl)-imino group,
• an N—(C1-4-alkyl)-N—(C2-4-alkyl)-amino group wherein the C2-4-alkyl moiety is substituted in β-, γ-, or δ-position with regard to the nitrogen atom of the amino group by the group R5, whilst R5 is as hereinbefore defined,
• a di-(C2-4-alkyl)-amino group wherein the two C2-4-alkyl moieties are substituted in each case in β-, γ-, or δ-position with regard to the nitrogen atom of the amino group by the group R5, whilst the substitutents may be identical or different and R5 is as hereinbefore defined,
• a C3-7-cycloalkylamino or C3-7-cycloalkyl-C1-3-alkylamino group wherein in each case the nitrogen atom may be substituted by a further C1-4-alkyl group,
• an amino or C1-4-alkylamino group wherein in each case the nitrogen atom is substituted by a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl, 1-(tetrahydrofuran-3-yl)-piperidin-4-yl, 1-(tetrahydropyran-3-yl)-piperidin-4-yl, 1-(tetrahydropyran-4-yl)-piperidin-4-yl, 3-pyrrolidinyl, 3-piperidinyl, 4-piperidinyl, 3-hexahydro-azepinyl or 4-hexahydro-azepinyl group optionally substituted by 1 to 3 C1-4-alkyl groups,
• a 4- to 7-membered alkyleneimino group optionally substituted by 1 to 4 C1-2-alkyl groups, which may be substituted by the group R5 either at a cyclic carbon atom or at one of the alkyl groups, whilst R5 is as hereinbefore defined,
• a piperidino group substituted by a tetrahydrofuranyl, tetrahydropyranyl or tetrahydrofuranylmethyl group,
• a 6- to 7-membered alkyleneimino group optionally substituted by 1 or 2 C1-2-alkyl groups wherein a methylene group in each case is replaced in the 4 position by an oxygen or sulfur atom, by an imino group substituted by the group R6, or by a sulfinyl or sulfonyl group, whilst
• R6 denotes a hydrogen atom, a C1-4-alkyl, 2-methoxy-ethyl, 3-methoxy-propyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-4-alkyl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl, formyl, C1-4-alkylcarbonyl, C1-4-alkylsulfonyl, aminocarbonyl, C1-4-alkylaminocarbonyl or di-(C1-4-alkyl)-aminocarbonyl group,
• an imidazolyl group optionally substituted by 1 to 3 methyl groups,
• a C5-7-cycloalkyl group wherein a methylene group is replaced by an oxygen or sulfur atom, by an imino group substituted by the group R6, by a sulfinyl or sulfonyl group, whilst R6 is as hereinbefore defined,
• or D together with E denotes a hydrogen, fluorine or chlorine atom,
• a C1-4-alkyl group optionally substituted by 1 to 5 fluorine atoms,
• a C3-6-cycloalkyl group,
• an aryl, heteroaryl, C1-4-alkylcarbonyl or arylcarbonyl group,
• a carboxy, C1-4-alkoxycarbonyl, aminocarbonyl, C1-4-alkylaminocarbonyl or di-(C1-4-alkyl)-aminocarbonyl group or
• a carbonyl which is substituted by a 4- to 7-membered alkyleneimino group, whilst in the abovementioned 6- to 7-membered alkyleneimino groups in each case a methylene group may be replaced in the 4 position by an oxygen or sulfur atom, by an imino group substituted by the group R6, by a sulfinyl or sulfonyl group, whilst R6 is as hereinbefore defined, and
• Rc denotes a C4-7-cycloalkoxy or C3-7-cycloalkyl-C1-6-alkoxy group wherein the cycloalkyl moiety in each case may be substituted by a C1-3-alkyl, hydroxy, C1-4-alkoxy, amino, C1-4-alkylamino, di-(C1-4-alkyl)-amino, pyrrolidino, piperidino, morpholino, piperazino, N—(C1-2-alkyl)-piperazino, hydroxy-C1-2-alkyl, C1-4-alkoxy-C1-2-alkyl, amino-C1-2-alkyl, C1-4-alkylamino-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, whilst the abovementioned monosubstituted cycloalkyl moieties may additionally be substituted by a C1-3-alkyl group,
• a tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4-yloxy or tetrahydrofuranylmethoxy group,
• an C2-4-alkoxy group substituted in β-, γ-, or δ-position with regard to the oxygen atom by an azetidin-1-yl, 4-methyl-homopiperazino or 4-ethyl-homopiperazino group,
• a 3-pyrrolidinyloxy, 2-pyrrolidinyl-C1-4-alkyloxy, 3-pyrrolidinyl-C1-4-alkyloxy, 3-piperidinyloxy, 4-piperidinyloxy, 2-piperidinyl-C1-4-alkyloxy, 3-piperidinyl-C1-4-alkyloxy, 4-piperidinyl-C1-4-alkyloxy, 3-hexahydro-azepinyloxy, 4-hexahydro-azepinyloxy, 2-hexahydro-azepinyl-C1-4-alkyloxy, 3-He-xahydro-azepinyl-C1-4-alkyloxy or 4-hexahydro-azepinyl-C1-4-alkyloxy group wherein in each case the cyclic nitrogen atom is substituted by the group R6, where R6 is as hereinbefore defined, whilst
• by the aryl moieties mentioned in the definition of the abovementioned groups is meant a phenyl group which in each case may be monosubstituted by R7, mono-, di- or trisubstituted by R8 or monosubstituted by R7 and additionally mono- or disubstituted by R8, wherein the substitutents may be identical or different and
• R7 denotes a cyano, carboxy, C1-4-alkoxycarbonyl, aminocarbonyl, C1-4-alkylaminocarbonyl, di-(C1-4-alkyl)-aminocarbonyl, C1-4-alkylsulfenyl, C1-4-alkylsulfinyl, C1-4-alkylsulfonyl, hydroxy, C1-4-alkylsulfonyloxy, trifluoromethyloxy, nitro, amino, C1-4-alkylamino, di-(C1-4-alkyl)-amino, C1-4-alkylcarbonylamino, N—(C1-4-alkyl)-C1-4-alkylcarbonylamino, C1-4-alkylsulfonylamino, N—(C1-4-alkyl)-C1-4-alkylsulfonylamino, aminosulfonyl, C1-4-alkylaminosulfonyl or di-(C1-4-alkyl)-aminosulfonyl group or a carbonyl group which is substituted by a 5- to 7-membered alkyleneimino group, whilst in the abovementioned 6- to 7-membered alkyleneimino groups in each case a methylene group in the 4 position may be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, imino or N—(C1-4-alkyl)-imino group, and
• R8 denotes a fluorine, chlorine, bromine or iodine atom, a C1-4-alkyl, trifluoromethyl or C1-4-alkoxy group or
• two groups R8, if they are bound to adjacent carbon atoms, together denote a C3-5-alkylene, methylenedioxy or 1,3-butadien-1,4-ylene group,
• and the heteroaryl groups mentioned in the definition of the abovementioned groups include a 5-membered heteroaromatic group which contains an imino group, an oxygen or sulfur atom or an imino group, an oxygen or sulfur atom and one or two nitrogen atoms, or
• a 6-membered heteroaromatic group which contains one, two or three nitrogen atoms,
• whilst the abovementioned 5-membered heteroaromatic groups may be substituted in each case by 1 or 2 methyl or ethyl groups and the abovementioned 6-membered heteroaromatic groups may be substituted in each case by 1 or 2 methyl or ethyl groups or by a fluorine, chlorine, bromine or iodine atom or by a trifluoromethyl, hydroxy, methoxy or ethoxy group,
• the tautomers, stereoisomers and salts thereof.