| Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them -> Monitor Keywords |
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Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing themRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Seven-membered Consisting Of One Nitrogen And Six Carbons, Additional Hetero Ring Attached Directly Or Indirectly To The Seven-membered Hetero Ring By Nonionic Bonding, The Additional Hetero Ring Is Six-membered And Contains Nitrogen, Plural Ring Hetero Atoms In The Additional Hetero Ring,Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070185091, Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] The present invention relates to bicyclic heterocycles of general formula the tautomers, the stereoisomers and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases, diseases of the lungs and respiratory tract, and the preparation thereof. [0002] In the above general formula I: R.sub.a denotes a hydrogen atom or a C.sub.1-4-alkyl group, R.sub.b denotes a phenyl, benzyl or 1-phenylethyl group wherein the phenyl nucleus is substituted in each case by the groups R.sub.1 to R.sub.3, whilst [0003] R.sub.1 and R.sub.2, which may be identical or different, in each case denote a hydrogen, fluorine, chlorine, bromine or iodine atom, [0004] a C.sub.1-4-alkyl, hydroxy, C.sub.1-4-alkoxy, C.sub.3-6-cycloalkyl, C.sub.4-6-cycloalkoxy, C.sub.2-5-alkenyl or C.sub.2-5-alkynyl group, [0005] an aryl, aryloxy, arylmethyl or arylmethoxy group, [0006] a C.sub.3-5-alkenyloxy or C.sub.3-5-alkynyloxy group, whilst the unsaturated moiety may not be linked to the oxygen atom, [0007] a C.sub.1-4-alkylsulfenyl, C.sub.1-4-alkylsulfinyl, C.sub.1-4-alkylsulfonyl, C.sub.1-4-alkylsulfonyloxy, trifluoromethylsulfenyl, trifluoromethylsulfinyl or trifluoromethylsulfonyl group, [0008] a methyl or methoxy group substituted by 1 to 3 fluorine atoms, [0009] an ethyl or ethoxy group substituted by 1 to 5 fluorine atoms, [0010] a cyano or nitro group or an amino group optionally substituted by one or two C.sub.1-4-alkyl groups, wherein the substitutents may be identical or different, or [0011] R.sub.1 together with R.sub.2, if they are bound to adjacent carbon atoms, denote a --CH.dbd.CH--CH.dbd.CH, --CH.dbd.CH--NH or --CH.dbd.N--NH group and [0012] R.sub.3 denotes a hydrogen, fluorine, chlorine or bromine atom, [0013] a C.sub.1-4-alkyl, trifluoromethyl or C.sub.1-4-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 C.sub.1-4-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 --SO.sub.2-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 --SO.sub.2-alkylene group to the adjacent group C in each case must take place via the carbonyl or sulfonyl group, a --CO--O-alkylene, --CO--NR.sub.4-alkylene or --SO.sub.2--NR.sub.4-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 [0014] R.sub.4 denotes a hydrogen atom or a C.sub.1-4-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, C.sub.1-4-alkylamino or di-(C.sub.1-4-alkyl)-amino group wherein the alkyl moieties may be identical or different, a C.sub.2-4-alkylamino group wherein the alkyl moiety is substituted in .beta.-, .gamma.-, or .delta.-position with regard to the nitrogen atom of the amino group by the group R.sub.5, whilst [0015] R.sub.5 denotes a hydroxy, C.sub.1-4-alkoxy, amino, C.sub.1-4-alkylamino or di-(C.sub.1-4-alkyl)-amino group, [0016] a 4- to 7-membered alkyleneimino group optionally substituted by one or two methyl groups or [0017] 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--(C.sub.1-4-alkyl)-imino group, an N--(C.sub.1-4-alkyl)-N--(C.sub.2-4-alkyl)-amino group wherein the C.sub.2-4-alkyl moiety is substituted in .beta.-, .gamma.-, or .delta.-position with regard to the nitrogen atom of the amino group by the group R.sub.5, whilst R.sub.5 is as hereinbefore defined, a di-(C.sub.2-4-alkyl)-amino group wherein the two C.sub.2-4-alkyl moieties are substituted in each case in .beta.-, .gamma.-, or .delta.-position with regard to the nitrogen atom of the amino group by the group R.sub.5, whilst the substitutents may be identical or different and R.sub.5 is as hereinbefore defined, a C.sub.3-7-cycloalkylamino or C.sub.3-7-cycloalkyl-C.sub.1-3-alkylamino group wherein in each case the nitrogen atom may be substituted by a further C.sub.1-4-alkyl group, an amino or C.sub.1-4-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 C.sub.1-4-alkyl groups, a 4- to 7-membered alkyleneimino group optionally substituted by 1 to 4 C.sub.1-2-alkyl groups, which may be substituted by the group R.sub.5 either at a cyclic carbon atom or at one of the alkyl groups, whilst R.sub.5 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 C.sub.1-2-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 R.sub.6, or by a sulfinyl or sulfonyl group, whilst [0018] R.sub.6 denotes a hydrogen atom, a C.sub.1-4-alkyl, 2-methoxyethyl, 3-methoxypropyl, C.sub.3-7-cycloalkyl, C.sub.3-7-cycloalkyl-C.sub.1-4-alkyl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl, formyl, C.sub.1-4-alkylcarbonyl, C.sub.1-4-alkylsulfonyl, aminocarbonyl, C.sub.1-4-alkylaminocarbonyl or di-(C.sub.1-4-alkyl)-aminocarbonyl group, an imidazolyl group optionally substituted by 1 to 3 methyl groups, a C.sub.5-7-cycloalkyl group wherein a methylene group is replaced by an oxygen or sulfur atom, by an imino group substituted by the group R.sub.6, by a sulfinyl or sulfonyl group, whilst R.sub.6 is as hereinbefore defined, or D together with E denotes a hydrogen, fluorine or chlorine atom, a C.sub.1-4-alkyl group optionally substituted by 1 to 5 fluorine atoms, a C.sub.3-6-cycloalkyl group, an aryl, heteroaryl, C.sub.1-4-alkylcarbonyl or arylcarbonyl group, a carboxy, C.sub.1-4-alkoxycarbonyl, aminocarbonyl, C.sub.1-4-alkylaminocarbonyl or di-(C.sub.1-4-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 R.sub.6, by a sulfinyl or sulfonyl group, whilst R.sub.6 is as hereinbefore defined, and R.sub.c denotes a C.sub.4-7-cycloalkoxy or C.sub.3-7-cycloalkyl-C.sub.1-6-alkoxy group wherein the cycloalkyl moiety in each case may be substituted by a C.sub.1-3-alkyl, hydroxy, C.sub.1-4-alkoxy, amino, C.sub.1-4-alkylamino, di-(C.sub.1-4-alkyl)-amino, pyrrolidino, piperidino, morpholino, piperazino, N--(C.sub.1-2-alkyl)-piperazino, hydroxy-C.sub.1-2-alkyl, C.sub.1-4-alkoxy-C.sub.1-2-alkyl, amino-C.sub.1-2-alkyl, C.sub.1-4-alkylamino-C.sub.1-2-alkyl, di-(C.sub.1-4-alkyl)-amino-C.sub.1-2-alkyl, pyrrolidino-C.sub.1-2-alkyl, piperidino-C.sub.1-2-alkyl, morpholino-C.sub.1-2-alkyl, piperazino-C.sub.1-2-alkyl or N--(C.sub.1-2-alkyl)-piperazino-C.sub.1-2-alkyl group, whilst the abovementioned monosubstituted cycloalkyl moieties may additionally be substituted by a C.sub.1-3-alkyl group, a tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4-yloxy or tetrahydrofuranylmethoxy group, an C.sub.2-4-alkoxy group substituted in .beta.-, .gamma.-, or .delta.-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-C.sub.1-4-alkyloxy, 3-pyrrolidinyl-C.sub.1-4-alkyloxy, 3-piperidinyloxy, 4-piperidinyloxy, 2-piperidinyl-C.sub.1-4-alkyloxy, 3-piperidinyl-C.sub.1-4-alkyloxy, 4-piperidinyl-C.sub.1-4-alkyloxy, 3-hexahydro-azepinyloxy, 4-hexahydro-azepinyloxy, 2-hexahydro-azepinyl-C.sub.1-4-alkyloxy, 3-He-xahydro-azepinyl-C.sub.1-4-alkyloxy or 4-hexahydro-azepinyl-C.sub.1-4-alkyloxy group wherein in each case the cyclic nitrogen atom is substituted by the group R.sub.6, where R.sub.6 is as hereinbefore defined, particularly those compounds of general formula I wherein R.sub.a, R.sub.b, A to C and X are as hereinbefore defined, E denotes an amino, C.sub.1-4-alkylamino or di-(C.sub.1-4-alkyl)-amino group wherein the alkyl moieties may be identical or different, a C.sub.2-4-alkylamino group wherein the alkyl moiety is substituted from position 2 by the group R.sub.5, whilst [0019] R.sub.5 denotes a hydroxy, C.sub.1-4-alkoxy, amino, C.sub.1-4-alkylamino or di-(C.sub.1-4-alkyl)-amino group, [0020] a 4- to 7-membered alkyleneimino group optionally substituted by one or two methyl groups or [0021] 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--(C.sub.1-4-alkyl)-imino group, an N--(C.sub.1-4-alkyl)-N--(C.sub.2-4-alkyl)-amino group wherein the C.sub.2-4-alkyl moiety is substituted from position 2 onwards by the group R.sub.5, where R.sub.5 is as hereinbefore defined, a di-(C.sub.2-4-alkyl)-amino group wherein the two C.sub.2-4-alkyl moieties are substituted in each case from position 2 onwards by the group R.sub.5, whilst the substitutents may be identical or different and R.sub.5 is as hereinbefore defined, a C.sub.3-7-cycloalkylamino or C.sub.3-7-cycloalkyl-C.sub.1-3-alkylamino group wherein in each case the nitrogen atom may be substituted by a further C.sub.1-4-alkyl group, an amino or C.sub.1-4-alkylamino group wherein in each case the nitrogen atom is substituted by a 3-pyrrolidinyl, 3-piperidinyl, 4-piperidinyl, 3-hexahydro-azepinyl or 4-hexahydro-azepinyl group optionally substituted by 1 to 3 C.sub.1-4-alkyl groups, a 4- to 7-membered alkyleneimino group optionally substituted by 1 to 4 C.sub.1-2-alkyl groups, which may be substituted by the group R.sub.5 either at a cyclic carbon atom or at one of the alkyl groups, whilst R.sub.5 is as hereinbefore defined, or a 6- to 7-membered alkyleneimino group optionally substituted by 1 or 2 C.sub.1-2-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 R.sub.6, or by a sulfinyl or sulfonyl group, whilst [0022] R.sub.6 denotes a hydrogen atom, a C.sub.1-4-alkyl, C.sub.3-7-cycloalkyl, C.sub.3-7-cycloalkyl-C.sub.1-4-alkyl, formyl, C.sub.1-4-alkylcarbonyl, C.sub.1-4-alkylsulfonyl, aminocarbonyl, C.sub.1-4-alkylaminocarbonyl or di-(C.sub.1-4-alkyl)-aminocarbonyl group, an imidazolyl group optionally substituted by 1 to 3 methyl groups, a C.sub.5-7-cycloalkyl group wherein a methylene group is replaced by an oxygen or sulfur atom, by an imino group substituted by the group R.sub.6, by a sulfinyl or sulfonyl group, whilst R.sub.6 is as hereinbefore defined, or D together with E denotes a hydrogen, fluorine or chlorine atom, a C.sub.1-4-alkyl group optionally substituted by 1 to 5 fluorine atoms, a C.sub.3-6-cycloalkyl group, an aryl, heteroaryl, C.sub.1-4-alkylcarbonyl or arylcarbonyl group, a carboxy, C.sub.1-4-alkoxycarbonyl, aminocarbonyl, C.sub.1-4-alkylaminocarbonyl or di-(C.sub.1-4-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 a methylene group may in each case be replaced in the 4 position by an oxygen or sulfur atom, by an imino group substituted by the group R.sub.6, by a sulfinyl or sulfonyl group, whilst R.sub.6 is as hereinbefore defined, and R.sub.c denotes a C.sub.4-7-cycloalkoxy or C.sub.3-7-cycloalkyl-C.sub.1-6-alkoxy group wherein the cycloalkyl moiety in each case may be substituted by a C.sub.1-3-alkyl, hydroxy, C.sub.1-4-alkoxy, amino, C.sub.1-4-alkylamino, di-(C.sub.1-4-alkyl)-amino, pyrrolidino, piperidino, morpholino, piperazino, N--(C.sub.1-2-alkyl)-piperazino, hydroxy-C.sub.1-2-alkyl, C.sub.1-4-alkoxy-C.sub.1-2-alkyl, amino-C.sub.1-2-alkyl, C.sub.1-4-alkylamino-C.sub.1-2-alkyl, di-(C.sub.1-4-alkyl)-amino-C.sub.1-2-alkyl, pyrrolidino-C.sub.1-2-alkyl, piperidino-C.sub.1-2-alkyl, morpholino-C.sub.1-2-alkyl, piperazino-C.sub.1-2-alkyl or N--(C.sub.1-2-alkyl)-piperazino-C.sub.1-2-alkyl group, whilst the abovementioned monosubstituted cycloalkyl moieties may additionally be substituted by a C.sub.1-3-alkyl group, or a 3-pyrrolidinyloxy, 2-pyrrolidinyl-C.sub.1-4-alkyloxy, 3-pyrrolidinyl-C.sub.1-4-alkyloxy, 3-piperidinyloxy, 4-piperidinyloxy, 2-piperidinyl-C.sub.1-4-alkyloxy, 3-piperidinyl-C.sub.1-4-alkyloxy, 4-piperidinyl-C.sub.1-4-alkyloxy, 3-hexahydro-azepinyloxy, 4-hexahydro-azepinyloxy, 2-hexahydro-azepinyl-C.sub.1-4-alkyloxy, 3-hexahydro-azepinyl-C.sub.1-4-alkyloxy or 4-hexahydro-azepinyl-C.sub.1-4-alkyloxy group wherein in each case the cyclic nitrogen atom is substituted by the group R.sub.6, where R.sub.6 is as hereinbefore defined. [0023] 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 R.sub.7, mono-, di- or trisubstituted by R.sub.8 or monosubstituted by R.sub.7 and additionally mono- or disubstituted by R.sub.8, wherein the substitutents may be identical or different and [0024] R.sub.7 denotes a cyano, carboxy, C.sub.1-4-alkoxycarbonyl, aminocarbonyl, C.sub.1-4-alkylaminocarbonyl, di-(C.sub.1-4-alkyl)-aminocarbonyl, C.sub.1-4-alkylsulfenyl, C.sub.1-4-alkylsulfinyl, C.sub.1-4-alkylsulfonyl, hydroxy, C.sub.1-4-alkylsulfonyloxy, trifluoromethyloxy, nitro, amino, C.sub.1-4-alkylamino, di-(C.sub.1-4-alkyl)-amino, C.sub.1-4-alkylcarbonylamino, N--(C.sub.1-4-alkyl)-C.sub.1-4-alkylcarbonylamino, C.sub.1-4-alkylsulfonylamino, N--(C.sub.1-4-alkyl)-C.sub.1-4-alkylsulfonylamino, aminosulfonyl, C.sub.1-4-alkylaminosulfonyl or di-(C.sub.1-4-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--(C.sub.1-4-alkyl)-imino group, and [0025] R.sub.8 denotes a fluorine, chlorine, bromine or iodine atom, a C.sub.1-4-alkyl, trifluoromethyl or C.sub.1-4-alkoxy group or [0026] two groups R.sub.8, if they are bound to adjacent carbon atoms, together denote a C.sub.3-5-alkylene, methylenedioxy or 1,3-butadien-1,4-ylene group. [0027] The heteroaryl groups mentioned in the definition of the abovementioned groups also 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 [0028] 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. [0029] Preferred compounds of the above general formula I are those wherein R.sub.a denotes a hydrogen atom, R.sub.b denotes a phenyl, benzyl or 1-phenylethyl group wherein the phenyl nucleus is substituted in each case by the groups R.sub.1 to R.sub.3, whilst [0030] R.sub.1 and R.sub.2, which may be identical or different, in each case denote a hydrogen, fluorine, chlorine, bromine or iodine atom, [0031] a C.sub.1-4-alkyl, hydroxy, C.sub.1-4-alkoxy, C.sub.3-6-cycloalkyl, C.sub.4-6-cycloalkoxy, C.sub.2-5-alkenyl or C.sub.2-5-alkynyl group, [0032] an aryl, aryloxy, arylmethyl or arylmethoxy group, [0033] a methyl or methoxy group substituted by 1 to 3 fluorine atoms, a cyano or nitro group and [0034] R.sub.3 denotes a hydrogen, fluorine, chlorine or bromine atom, [0035] a C.sub.1-4-alkyl, trifluoromethyl or C.sub.1-4-alkoxy group, X denotes a methine group substituted by a cyano group or a nitrogen atom, A denotes an imino group, B denotes a carbonyl or sulfonyl group, C denotes a 1,3-allenylene, 1,1- or 1,2-vinylene group, an ethynylene or 1,3-butadien-1,4-ylene group, D denotes an alkylene, --CO-alkylene or --SO.sub.2-alkylene group wherein the alkylene moiety in each case contains 1 to 4 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 --SO.sub.2-alkylene group to the adjacent group C in each case must take place via the carbonyl or sulfonyl group, a --CO--O-alkylene, --CO--NR.sub.4-alkylene or --SO.sub.2--NR.sub.4-alkylene group wherein the alkylene moiety in each case contains 1 to 4 carbon atoms, whilst the linking to the adjacent group C in each case must take place via the carbonyl or sulfonyl group, wherein [0036] R.sub.4 denotes a hydrogen atom or a C.sub.1-4-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 a di-(C.sub.1-4-alkyl)-amino group wherein the alkyl moieties may be identical or different, an N--(C.sub.1-4-alkyl)-N--(C.sub.2-4-alkyl)-amino group wherein the C.sub.2-4-alkyl moiety is substituted in .beta.-, .gamma.-, or .delta.-position with regard to the nitrogen atom of the amino group by the group R.sub.5, where [0037] R.sub.5 denotes a hydroxy, C.sub.1-4-alkoxy or di-(C.sub.1-4-alkyl)-amino group, [0038] a 4- to 7-membered alkyleneimino group optionally substituted by one or two methyl groups or [0039] 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, or by a sulfinyl, sulfonyl or N--(C.sub.1-4-alkyl)-imino group, a di-(C.sub.2-4-alkyl)-amino group wherein the two C.sub.2-4-alkyl moieties in each case are substituted in .beta.-, .gamma.-, or .delta.-position with regard to the nitrogen atom of the amino group by the group R.sub.5, wherein the substitutents may be identical or different and R.sub.5 is as hereinbefore defined, a C.sub.3-7-cycloalkylamino or C.sub.3-7-cycloalkyl-C.sub.1-3-alkylamino group wherein in each case the nitrogen atom is substituted by a further C.sub.1-4-alkyl group, a C.sub.1-4-alkylamino group wherein 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, N--(C.sub.1-2-alkyl)-3-pyrrolidinyl, N--(C.sub.1-2-alkyl)-3-piperidinyl, N--(C.sub.1-2-alkyl)-4-piperidinyl, N--(C.sub.1-2-alkyl)-3-hexahydro-azepinyl or N--(C.sub.1-2-alkyl)-4-hexahydro-azepinyl group, an 4- to 7-membered alkyleneimino group optionally substituted by 1 to 4 methyl groups, which may be substituted either at a cyclic carbon atom or at one of the methyl groups by the group R.sub.5, where R.sub.5 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 methyl groups wherein in each case a methylene group is replaced in the 4 position by an oxygen or sulfur atom, by an imino group substituted by the group R.sub.6, by a sulfinyl or sulfonyl group, whilst [0040] R.sub.6 denotes a C.sub.1-4-alkyl, 2-methoxyethyl, 3-methoxypropyl, C.sub.3-7-cycloalkyl, C.sub.3-7-cycloalkyl-C.sub.1-4-alkyl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl, formyl, C.sub.1-4-alkylcarbonyl, C.sub.1-4-alkylsulfonyl, aminocarbonyl, C.sub.1-4-alkylaminocarbonyl or di-(C.sub.1-4-alkyl)-aminocarbonyl group, a C.sub.5-7-cycloalkyl group wherein a methylene group is replaced by an oxygen or sulfur atom, by an imino group substituted by the group R.sub.6, or by a sulfinyl or sulfonyl group, where R.sub.6 is as hereinbefore defined, or D together with E denotes a hydrogen, fluorine or chlorine atom, a C.sub.1-4-alkyl group optionally substituted by 1 to 5 fluorine atoms, a C.sub.3-6-cycloalkyl group, an aryl, C.sub.1-4-alkylcarbonyl or arylcarbonyl group, a carboxy, C.sub.1-4-alkoxycarbonyl, aminocarbonyl, C.sub.1-4-alkylaminocarbonyl or di-(C.sub.1-4-alkyl)-aminocarbonyl group or a carbonyl group 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 in the 4 position may be replaced by an oxygen or sulfur atom, by an imino group substituted by the group R.sub.6, or by a sulfinyl or sulfonyl group, where R.sub.6 is as hereinbefore defined, and R.sub.c denotes a C.sub.4-7-cycloalkoxy or C.sub.3-7-cycloalkyl-C.sub.1-6-alkoxy group wherein the cycloalkyl moiety in each case may be substituted by a C.sub.1-3-alkyl, hydroxy, C.sub.1-4-alkoxy, di-(C.sub.1-4-alkyl)-amino, pyrrolidino, piperidino, morpholino, N--(C.sub.1-2-alkyl)-piperazino, hydroxy-C.sub.1-2-alkyl, C.sub.1-4-alkoxy-C.sub.1-2-alkyl, di-(C.sub.1-4-alkyl)-amino-C.sub.1-2-alkyl, pyrrolidino-C.sub.1-2-alkyl, piperidino-C.sub.1-2-alkyl, morpholino-C.sub.1-2-alkyl or N--(C.sub.1-2-alkyl)-piperazino-C.sub.1-2-alkyl group, whilst the abovementioned monosubstituted cycloalkyl moieties may additionally be substituted by a C.sub.1-3-alkyl group, a tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4-yloxy or tetrahydrofuranylmethoxy group, an C.sub.2-4-alkoxy group substituted in .beta.-, .gamma.-, or .delta.-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-C.sub.1-4-alkyloxy, 3-pyrrolidinyl-C.sub.1-4-alkyloxy, 3-piperidinyloxy, 4-piperidinyloxy, 2-piperidinyl-C.sub.1-4-alkyloxy, 3-piperidinyl-C.sub.1-4-alkyloxy, 4-piperidinyl-C.sub.1-4-alkyloxy, 3-hexahydro-azepinyloxy, 4-hexahydro-azepinyloxy, 2-hexahydro-azepinyl-C.sub.1-4-alkyloxy, 3-hexahydro-azepinyl-C.sub.1-4-alkyloxy or 4-hexahydro-azepinyl-C.sub.1-4-alkyloxy group wherein in each case the cyclic nitrogen atom is substituted by the group R.sub.6, where R.sub.6 is as hereinbefore defined, whilst by the aryl moieties mentioned in the definition of the abovementioned groups is meant a phenyl group which may in each case be monosubstituted by R.sub.7, mono-, di- or trisubstituted by R.sub.8 or monosubstituted by R.sub.7 and additionally mono- or disubstituted by R.sub.8, wherein the substitutents may be identical or different and [0041] R.sub.7 denotes a cyano, carboxy, C.sub.1-4-alkoxycarbonyl, aminocarbonyl, C.sub.1-4-alkylaminocarbonyl, di-(C.sub.1-4-alkyl)-aminocarbonyl, C.sub.1-4-alkylsulfenyl, C.sub.1-4-alkylsulfinyl, C.sub.1-4-alkylsulfonyl, hydroxy, C.sub.1-4-alkylsulfonyloxy, trifluoromethyloxy, nitro, amino, C.sub.1-4-alkylamino, di-(C.sub.1-4-alkyl)-amino, C.sub.1-4-alkylcarbonylamino, N--(C.sub.1-4-alkyl)-C.sub.1-4-alkylcarbonylamino, C.sub.1-4-alkylsulfonylamino, N--(C.sub.1-4-alkyl)-C.sub.1-4-alkylsulfonylamino, aminosulfonyl, C.sub.1-4-alkylaminosulfonyl or di-(C.sub.1-4-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 may be replaced in the 4 position by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, imino or N--(C.sub.1-4-alkyl)-imino group, and [0042] R.sub.8 denotes a fluorine, chlorine, bromine or iodine atom, a C.sub.1-4-alkyl, trifluoromethyl or C.sub.1-4-alkoxy group or [0043] two groups R.sub.8, if they are bound to adjacent carbon atoms, together denote a C.sub.3-5-alkylene, methylenedioxy or 1,3-butadien-1,4-ylene group, the tautomers, stereoisomers and salts thereof. [0044] Particularly preferred compounds of the above general formula I are those wherein R.sub.a denotes a hydrogen atom, R.sub.b denotes a phenyl, benzyl or 1-phenylethyl group wherein the phenyl nucleus is substituted in each case by the groups R.sub.1 and R.sub.2, where [0045] R.sub.1 and R.sub.2, which may be identical or different, in each case denote a hydrogen, fluorine, chlorine or bromine atom, [0046] a methyl, trifluoromethyl or methoxy group, X denotes a nitrogen atom, A denotes an imino group, B denotes a carbonyl group, C denotes a 1,2-vinylene group, an ethynylene or 1,3-butadien-1,4-ylene group, D denotes a C.sub.1-4-alkylene 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 group, E denotes a di-(C.sub.1-4-alkyl)-amino group wherein the alkyl moieties may be identical or different, an N--(C.sub.1-4-alkyl)-N--(C.sub.2-4-alkyl)-amino group wherein the C.sub.2-4-alkyl moiety is substituted in .beta.-, .gamma.-, or .delta.-position with regard to the nitrogen atom of the amino group by the group R.sub.5, whilst [0047] R.sub.5 denotes a hydroxy, C.sub.1-3-alkoxy or di-(C.sub.1-3-alkyl)-amino group, [0048] a pyrrolidino, piperidino or morpholino group, a di-(C.sub.2-4-alkyl)-amino group wherein the two C.sub.2-4-alkyl moieties in each case are substituted in .beta.-, .gamma.-, or .delta.-position with regard to the nitrogen atom of the amino group by the group R.sub.5, wherein the substitutents may be identical or different and R.sub.5 is as hereinbefore defined, an C.sub.1-4-alkylamino group substituted at the nitrogen atom by a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl, 1-(C.sub.1-2-alkyl)-pyrrolidin-3-yl, 1-(C.sub.1-2-alkyl)-piperidin-3-yl, 1-(C.sub.1-2-alkyl)-piperidin-4-yl, 1-(tetrahydrofuran-3-yl)piperidin-4-yl, 1-(tetrahydropyran-3-yl)piperidin-4-yl or 1-(tetrahydropyran-4-yl)piperidin-4-yl group, a C.sub.3-5-cycloalkylamino or C.sub.3-5-cycloalkyl-C.sub.1-3-alkylamino group wherein in each case the nitrogen atom is substituted by a further C.sub.1-3-alkyl group, a 5- to 7-membered alkyleneimino group optionally substituted by 1 or 2 methyl groups which may be substituted either at a cyclic carbon atom or at one or the methyl groups by the group R.sub.5, where R.sub.5 is as hereinbefore defined, or a piperidino group substituted by a tetrahydrofuranyl, tetrahydropyranyl or tetrahydrofuranylmethyl group, a piperidino group optionally substituted by 1 or 2 methyl groups wherein the methylene group is replaced in the 4 position by an oxygen or sulfur atom, by sulfinyl or sulfonyl group or by an imino group substituted by the group R.sub.6, whilst [0049] R.sub.6 denotes a C.sub.1-3-alkyl, 2-methoxyethyl, 3-methoxypropyl, C.sub.3-6-cycloalkyl, C.sub.3-6-cycloalkyl-C.sub.1-3-alkyl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl, C.sub.1-3-alkylcarbonyl, C.sub.1-3-alkylsulfonyl, aminocarbonyl, C.sub.1-3-alkylaminocarbonyl or di-(C.sub.1-3-alkyl)-aminocarbonyl group, or D together with E denotes a hydrogen atom, a C.sub.1-3-alkyl group, an aryl or C.sub.1-4-alkylcarbonyl group or a C.sub.1-4-alkoxycarbonyl group, R.sub.c denotes a C.sub.4-7-cycloalkoxy or C.sub.3-7-cycloalkyl-C.sub.1-4-alkoxy group wherein the cycloalkyl moiety in each case may be substituted by a C.sub.1-3-alkyl or C.sub.1-3-alkoxy group, a tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4-yloxy or tetrahydrofuranylmethoxy group, an C.sub.2-4-alkoxy group substituted in .beta.-, .gamma.-, or .delta.-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-C.sub.1-3-alkyloxy, 3-pyrrolidinyl-C.sub.1-3-alkyloxy, 3-piperidinyloxy, 4-piperidinyloxy, 2-piperidinyl-C.sub.1-3-alkyloxy, 3-piperidinyl-C.sub.1-3-alkyloxy, 4-piperidinyl-C.sub.1-3-alkyloxy, 3-hexahydro-azepinyloxy, 4-hexahydro-azepinyloxy, 2-hexahydro-azepinyl-C.sub.1-3-alkyloxy, 3-hexahydro-azepinyl-C.sub.1-3-alkyloxy or 4-hexahydro-azepinyl-C.sub.1-3-alkyloxy group wherein in each case the cyclic nitrogen atom is substituted by a methyl or ethyl group, whilst by the aryl moieties mentioned in the definition of the abovementioned groups is meant a phenyl group which may be mono-, di- or trisubstituted by R.sub.8, wherein the substitutents may be identical or different and [0050] R.sub.8 denotes a fluorine, chlorine, bromine or iodine atom, a C.sub.1-4-alkyl, trifluoromethyl or C.sub.1-4-alkoxy group, the tautomers, stereoisomers and salts thereof. [0051] Most particularly preferred compounds of the above general formula I are those wherein R.sub.a denotes a hydrogen atom, R.sub.b denotes a phenyl, benzyl or 1-phenylethyl group, whilst the phenyl nucleus is substituted in each case by the radicals R.sub.1 and R.sub.2, whilst [0052] R.sub.1 and R.sub.2, which may be identical or different, each denotes a hydrogen, fluorine, chlorine or bromine atom, X denotes a nitrogen atom, A denotes an imino group, B denotes a carbonyl group, C denotes a 1,2-vinylene, ethinylene or 1,3-butadien-1,4-ylene group, D denotes an C.sub.1-3-alkylene group, E denotes a Di-(C.sub.1-4-alkyl)-amino group, wherein the alkyl moieties may be identical or different, a methylamino or ethylamino group each substituted at the nitrogen atom by a 2-methoxyethyl, 1-methoxy-2-propyl, 2-methoxypropyl, 3-methoxypropyl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, tetrahydrofuran-2-ylmethyl, 1-methylpiperidin-4-yl, 1-ethylpiperidin-4-yl, 1-(tetrahydrofuran-3-yl)piperidin-4-yl, cyclopropyl or cyclopropylmethyl group, a Bis-(2-methoxyethyl)amino group, a pyrrolidino, piperidino or morpholino group each optionally substituted by one or two methyl groups, a piperazino group substituted in 4-position by a methyl, ethyl, cyclopropyl, cyclopropylmethyl, 2-methoxyethyl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or tetrahydrofuran-2-ylmethyl group, a thiomorpholino, S-oxidothiomorpholino or S,S-dioxidothiomorpholino group, a 2-(methoxymethyl)pyrrolidino, 2-(ethoxymethyl)pyrrolidino, 4-hydroxypiperidino, 4-methoxypiperidino, 4-ethoxypiperidino, 4-(tetrahydrofuran-3-yl)piperidino or 4-morpholinopiperidino group or D together with E denote a hydrogen atom, a methyl, phenyl, methoxycarbonyl or ethoxycarbonyl group and R.sub.c denotes a cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy or cyclohexylmethoxy group, a cyclobutyloxy, cyclopentyloxy or cyclohexyloxy group, a tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy or tetrahydrofuran-2-ylmethoxy group, a straight chained C.sub.2-4-alkoxy group terminally substituted by an azetidin-1-yl, 4-methyl-homopiperazino or 4-ethyl-homopiperazino group, a 1-methylpiperidin-4-yloxy or 1-ethylpiperidin-4-yloxy group, a (1-methylpiperidin-4-yl)-C.sub.1-3-alkyloxy or (1-ethylpiperidin-4-yl)-C.sub.1-3-alkyloxy group, especially those compounds wherein R.sub.a denotes a hydrogen atom, R.sub.b denotes a 1-phenylethyl group or a phenyl group wherein the phenyl nucleus is substituted by the radicals R.sub.1 and R.sub.2, whilst [0053] R.sub.1 and R.sub.2, which may be identical or different, each denote a hydrogen, fluorine, chlorine or bromine atom, X denotes a nitrogen atom, A denotes an imino group, B denotes a carbonyl group, C denotes a 1,2-vinylene, ethinylene or 1,3-butadien-1,4-ylene group, D denotes a methylene group, E denotes a dimethylamino, diethylamino, bis(2-methoxyethyl)amino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, N-methyl-N-cyclopropyl-amino, N-methyl-N-cyclopropylmethyl-amino, N-methyl-N-(1-methoxy-2-propyl)amino, N-methyl-N-(2-methoxypropyl)amino, N-methyl-N-(3-methoxypropyl)amino-, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino or N-methyl-N-(1-methylpiperidin-4-yl)amino group, a pyrrolidino, piperidino or morpholino group each optionally substituted by one or two methyl groups, a piperazino group substituted in 4-position by a methyl, ethyl, cyclopropylmethyl or 2-methoxyethyl group, a S-oxidothiomorpholino group, a 2-(methoxymethyl)pyrrolidino, 4-hydroxypiperidino or 4-methoxypiperidino group or D together with E denote a hydrogen atom, a methyl, phenyl or ethoxycarbonyl group, and R.sub.c denotes a cyclopropylmethoxy, cyclobutyloxy or cyclopentyloxy group, a tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy or tetrahydrofuran-2-ylmethoxy group, a straight chained C.sub.2-4-alkoxy group terminally substituted by an azetidin-1-yl or 4-methyl-homopiperazino group, a 1-methylpiperidin-4-yloxy group or a (1-methylpiperidin-4-yl)-C.sub.1-3-alkyloxy group, the tautomers, stereoisomers and salts thereof. [0054] The following particularly valuable compounds of general formula I may be mentioned by way of example: [0055] (a) 4-[(3-Chloro-4-fluorophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy- ]-6-[(vinylcarbonyl)amino]quinazoline, [0056] (b) 4-[(3-Chloro-4-fluorophenyl)amino]-6-{[4-(N,N-diethylamino)-1-oxo-2-buten- -1-yl]amino}-7-cyclopropylmethoxyquinazoline and [0057] (c) 4-[(3-Chloro-4-fluorophenyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1- -yl]amino}-7-cyclopropylmethoxyquinazoline as well as the salts thereof. [0058] The compounds of general formula I may be prepared, for example, by the following processes: a) reacting a compound of general formula wherein R.sub.a to R.sub.c, A and X are as hereinbefore defined, with a compound of general formula Z.sub.1-B-C-D-E (III) wherein B to E are as hereinbefore defined and Z.sub.1 denotes a leaving group such as a halogen atom, e.g., a chlorine or bromine atom, or a hydroxy group. [0059] The reaction is optionally carried out in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuran, benzene/-tetrahydrofuran or dioxane optionally in the presence of an inorganic or organic base and optionally in the presence of a dehydrating agent, expediently at temperatures between -50.degree. C. and 150.degree. C., preferably at temperatures between -20.degree. C. and 80.degree. C. [0060] With a compound of general formula III wherein Z.sub.1 denotes a leaving group, the reaction is optionally carried out in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuran, benzene/tetrahydrofuran or dioxane conveniently in the presence of a tertiary organic base such as triethylamine, pyridine or 2-dimethylaminopyridine, in the presence of N-ethyl-diisopropylamine (Hunig base), whilst these organic bases may simultaneously also act as solvent, or in the presence of an inorganic base such as sodium carbonate, potassium carbonate or sodium hydroxide solution expediently at temperatures between -50.degree. C. and 150.degree. C., preferably at temperatures between -20.degree. C. and 80.degree. C. Continue reading about Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them... 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