CA2540501A1 - Quinoline derivatives and quinazoline derivatives, medicaments containing said compounds, use thereof, and method for the production thereof - Google Patents
Quinoline derivatives and quinazoline derivatives, medicaments containing said compounds, use thereof, and method for the production thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Abstract
The invention relates to bicyclic heterocycles of general formula (I), wherein Ra, Rb, Rc, Rd, and X are defined as indicated in claim 1, the tautomers, stereoisomers, mixtures, and salts thereof, especially the physiologically acceptable salts thereof with inorganic or organic acids that have valuable pharmacological properties, particularly an inhibitory effect on the signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, above all tumor diseases, benign prostate hyperplasia (BPH), and diseases of the lung and respiratory tract, and the production thereof.
Claims (10)
1. Bicyclic heterocycles of the general formula in which R a is a hydrogen atom or a C1-4-alkyl group, R b is a 1-phenylethyl group, in which the phenyl nucleus is in each case substituted by the groupgroups R1 to R3, where R1 and R2, which can be identical or different, are in each case a hydrogen, fluorine, chlorine, bromine or iodine atom, a C1-4-alkyl, hydroxyl, C1-4-alkoxy, C2-3-alkenyl or C2-3-alkynyl group, an aryl, aryloxy, arylmethyl or arylmethoxy group, a heteroaryl, heteroaryloxy, heteroarylmethyl or heteroarylmethoxy group, a methyl or methoxy group substituted by 1 to 3 fluorine atoms or a cyano, nitro or amino group, and R3 is a hydrogen, fluorine, chlorine or bromine atom or a methyl or trifluoromethyl group, R c is a cyclobutyl, cyclopentyl or cyclohexyl group, which is in each case substituted by a group R4-N-R5, where R4 is a hydrogen atom or a C1-3-alkyl group and R5 is a hydrogen atom or a C1-3-alkyl group, an aminocarbonyl-C1-3-alkyl, C1-3-alkylaminocarbonyl-C1-3-alkyl, di-(C1-3-alkyl)-aminocarbonyl-C1-3-alkyl, pyrrolidin-1-ylcarbonyl-C1-3-alkyl, piperidin-1-ylcarbonyl-C1-3-alkyl, homopiperidin-1-ylcarbonyl-C1-3-alkyl, morpholin-4-ylcarbonyl-C1-3-alkyl, homomorpholin-4-ylcarbonyl-C1-3-alkyl, piperazin-1-ylcarbonyl-C1-3-alkyl, 4-C1-3-alkylpiperazin-1-ylcarbonyl-C1-3-alkyl, homopiperazin-1-yl-carbonyl-C1-3-alkyl or a 4-C1-3-alkylhomopiperazin-1-ylcarbonyl-C1-3-alkyl group, a hydroxy-C2-4-alkyl, C1-3-alkyloxy-C2-4-alkyl, C1-4-alkyloxycarbonylamino-C2-alkyl, amino-C2-4-alkyl, C1-3-alkylamino-C2-4-alkyl, di-(C1-3-alkyl)amino-C2-4-alkyl, C1-3-alkylcarbonylamino-C2-4-alkyl, aminocarbonylamino-C2-4-alkyl, C1-3-alkyl-aminocarbonylamino-C2-4-alkyl, di-(C1-3-alkyl)aminocarbonylamino-C2-4-alkyl, pyrrolidin-1-ylcarbonylamino-C2-4-alkyl, piperidin-1-ylcarbonylamino-C2-4-alkyl, morpholin-4-ylcarbonylamino-C2-4-alkyl, C1-3-alkylsulphonyl-C2-4-alkyl or a C1-3-alkylsulphonylamino-C2-4-alkyl group, a (2-oxopyrrolidin-1-yl)-C2-4-alkyl, (2-oxopiperidin-1-yl)-C2-4-alkyl, (3-oxo-morpholin-4-yl)-C2-4-alkyl, (2-oxoimidazolidin-1-yl)-C2-4-alkyl, (2-oxo-3-C1-3-alkyl-imidazolidin-1-yl)-C2-4-alkyl, (2-oxohexahydropyrimidin-1-yl)-C2-4-alkyl or a (2-oxo-3-C1-3-alkylhexahydropyrimidin-1-yl)-C2-4-alkyl group, a C1-4-alkylsulphonyl, chloro-C1-4-alkylsulphonyl, bromo-C1-4-alkylsulphonyl, amino-C1-4-alkylsulphonyl, C1-3-alkylamino-C1-4-alkylsulphonyl, di-(C1-3-alkyl)-amino-C1-4-alkylsulphonyl, (pyrrolidin-1-yl)-C1-4-alkylsulphonyl, (piperidin-1-yl)-C1-4-alkylsulphonyl, (homopiperidin-1-yl)-C1-4-alkylsulphonyl, (morpholin-4-yl)-C1-4-alkylsulphonyl, (homomorpholin-4-yl)-C1-4-alkylsulphonyl, (piperazin-1-yl)-C1-4-alkylsulphonyl, (4-C1-3-alkylpiperazin-1-yl)-C1-4-alkylsulphonyl, (homo-piperazin-1-yl)-C1-4-alkylsulphonyl or a (4-C1-3-alkylhomopiperazin-1-yl)-C1-4-alkylsulphonyl group, a C1-4-alkyloxycarbonyl group, a formyl, C1-4-alkylcarbonyl, C1-3-alkyloxy-C1-4-alkylcarbonyl, tetrahydrofuranyl-carbonyl, tetrahydropyranylcarbonyl, amino-C1-4-alkylcarbonyl, C1-3-alkylamino-C1-4-alkylcarbonyl, di-(C1-3-alkyl)amino-C1-4-alkylcarbonyl, pyrrolidin-1-yl-C1-4-alkylcarbonyl, piperidin-1-yl-C1-4-alkylcarbonyl, (homopiperidin-1-yl)-C1-4-alkylcarbonyl, morpholin-4-yl-C1-4-alkylcarbonyl, (homomorpholin-4-yl)-C1-4-alkylcarbonyl, (piperazin-1-yl)-C1-4-alkylcarbonyl, (4-C1-3-alkylpiperazin-1-yl)-C1-4-alkylcarbonyl, (homopiperazin-1-yl)-C1-4-alkylcarbonyl, (4-C1-3-alkyl-homopiperazin-1-yl)-C1-4-alkylcarbonyl or a C1-3-alkylsulphonyl-C1-4-alkylcarbonyl group, a cyano, aminocarbonyl, C1-3-alkylaminocarbonyl, di-(C1-3-alkyl)aminocarbonyl, (C1-3-alkyloxy-C2-4-alkyl)aminocarbonyl, N-(C1-3-alkyl)-N-(C1-3-alkyloxy-C2-4-alkyl)-aminocarbonyl, arylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, homopiperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, homomorpholin-4-yl-carbonyl, 2-oxa-5-azabicyclo[2.2.1]hept-5-ylcarbonyl, 3-oxa-8-azabicyclo[3.2.1]-oct-8-ylcarbonyl, 8-oxa-3-azabicyclo[3.2.1]oct-3-ylcarbonyl, piperazin-1-yl-carbonyl, 4-C1-3-alkylpiperazin-1-ylcarbonyl, homopiperazin-1-ylcarbonyl, 4-C1-3-alkylhomopiperazin-1-ylcarbonyl, aminosulphonyl, C1-3-alkylaminosulphonyl, di-(C1-3-alkyl)aminosulphonyl, pyrrolidin-1-yl-sulphonyl, piperidin-1-ylsulphonyl, homopiperidin-1-ylsulphonyl, morpholin-4-ylsulphonyl, homomorpholin-4-yl-sulphonyl, piperazin-1-ylsulphonyl, 4-C1-3-alkylpiperazin-1-ylsulphonyl, homo-piperazin-1-ylsulphonyl or a 4-C1-3-alkylhomopiperazin-1-ylsulphonyl group, a cyclobutyl, cyclopentyl or cyclohexyl group, which is in each case substituted by a group R6, where R6 is a 2-oxopyrrolidin-1-yl, 2-oxopiperidin-1-yl, 3-oxomorpholin-4-yl, 2-oxo-imidazolidin-1-yl, 2-oxo-3-C1-3-alkylimidazolidin-1-yl, 2-oxohexahydropyrimidin-1-yl or a 2-oxo-3-C1-3-alkylhexahydropyrimidin-1-yl group, an azetidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a pyrrolidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a piperidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a piperidin-4-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, or a tetrahydrofuran-3-yl, tetrahydropyran-3-yl or tetrahydropyran-4-yl group, R d is a hydrogen atom or a fluorine, chlorine or bromine atom, a hydroxyl group, a C1-4-alkyloxy group, a methoxy group substituted by 1 to 3 fluorine atoms, an ethyloxy group substituted by 1 to 5 fluorine atoms, a C2-4-alkyloxy group, which is substituted by the group R6 or R7, where R6 is defined as mentioned above and R7 is a hydroxyl, C1-3-alkyloxy, C3-6-cycloalkyloxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)amino, bis(2-methoxyethyl)amino, pyrrolidin-1-yl, piperidin-1-yl, homopiperidin-1-yl, morpholin-4-yl, homomorpholin-4-yl, 2-oxa-5-azabicyclo-
[2.2.1 ]hept-5-yl, 3-oxa-8-azabicyclo[3.2.1 ]oct-8-yl, 8-oxa-3-azabicyclo[3.2.1 ]oct-3-yl, piperazin-1-yl, 4-C1-3-alkylpiperazin-1-yl, homopiperazin-1-yl or C1-3-alkyl-homopiperazin-1-yl group, or a formylamino, C1-4-alkylcarbonylamino, C1-3-alkyloxy-C1-3-alkylcarbonylamino, C1-4-alkyloxycarbonylamino, aminocarbonylamino, C1-3-alkylaminocarbonylamino, di-(C1-3-alkyl)aminocarbonylamino, pyrrolidin-1-ylcarbonylamino, piperidin-1-yl-carbonylamino, piperazin-1-ylcarbonylamino, 4-C1-3-alkylpiperazin-1-ylcarbonyl-amino, morpholin-4-ylcarbonylamino or a C1-4-alkylsulphonylamino group, a C3-7-cycloalkyloxy or C3-7-cycloalkyl-C1-4-alkyloxy group, a tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy or tetrahydropyran-4-yloxy group, a tetrahydrofuranyl-C1-4-alkyloxy or tetrahydropyranyl-C1-4-alkyloxy group, a C1-4-alkoxy group, which is substituted by a pyrrolidinyl, piperidinyl or homopiperidinyl group substituted in the 1- position by the group R8, where R8 is a hydrogen atom or a C1-3-alkyl group, or a C1-4-alkoxy group, which is substituted by a morpholinyl group substituted in the 4-position by the group R8, where R8 is defined as mentioned above, and X is a methine group substituted by a cyano group or is a nitrogen atom, and where the aryl groups mentioned in the definition of the abovementioned groupgroups are in each case to be understood as meaning a phenyl group which is mono- or disubstituted by R9, where the substituents can be identical or different and R9 is a hydrogen atom, a fluorine, chlorine, bromine, or iodine atom or a C1-3-alkyl, hydroxyl, C1-3-alkyloxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy or cyano group, the heteroaryl groups mentioned in the definition of the abovementioned groupgroups are to be understood as meaning a pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl group, where the abovementioned heteroaryl groups are in each case mono- or disubstituted by the group R9, where the substituents can be identical or different and R9 is defined as mentioned above, and the abovementioned pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl groups can in each case be substituted by one or two C1-3-alkyl groups, and if not mentioned otherwise, the abovementioned alkyl groups can be straight-chain or branched, their tautomers, their stereoisomers, their mixtures and their salts.
2. Bicyclic heterocycles of the general formula I according to Claim 1, in which R a is a hydrogen atom, R b is a 1-phenylethyl group, R c is a cyclopentyl group, which is substituted in the 3-position by a group R4-N-R5, where R4 is a hydrogen atom or a C1-3-alkyl group and R5 is a hydrogen atom or a C1-3-alkyl group, an aminocarbonyl-C1-3-alkyl, C1-3-alkylaminocarbonyl-C1-3-alkyl, di-(C1-3-alkyl)-aminocarbonyl-C1-3-alkyl, pyrrolidin-1-ylcarbonyl-C1-3-alkyl, piperidin-1-ylcarbonyl-C1-3-alkyl, piperazin-1-ylcarbonyl-C1-3-alkyl, 4-C1-3-alkylpiperazin-1-ylcarbonyl-C1-3-alkyl or morpholin-4-ylcarbonyl-C1-3-alkyl group, a hydroxy-C2-4-alkyl, C1-3-alkyloxy-C2-4-alkyl, C1-4-alkyloxycarbonylamino-C2-alkyl, amino-C2-4-alkyl, C1-3-alkylamino-C2-4-alkyl, di-(C1-3-alkyl)amino-C2-4-alkyl, C1-3-alkylcarbonylamino-C2-4-alkyl, aminocarbonylamino-C2-4-alkyl, C1-3-alkyl-aminocarbonylamino-C2-4-alkyl, di-(C1-3-alkyl)aminocarbonylamino-C2-4-alkyl, morpholin-4-ylcarbonylamino-C2-4-alkyl, C1-3-alkylsulphonyl-C2-4-alkyl or C1-3-alkylsulphonylamino-C2-4-alkyl group, a (2-oxopyrrolidin-1-yl)-C2-4-alkyl, (2-oxopiperidin-1-yl)-C2-4-alkyl, (3-oxo-morpholin-4-yl)-C2-4-alkyl, (2-oxoimidazolidin-1-yl)-C2-4-alkyl, (2-oxo-3-methyl-imidazolidin-1-yl)-C2-4-alkyl, (2-oxohexahydropyrimidin-1-yl)-C2-4-alkyl or (2-oxo-
2. Bicyclic heterocycles of the general formula I according to Claim 1, in which R a is a hydrogen atom, R b is a 1-phenylethyl group, R c is a cyclopentyl group, which is substituted in the 3-position by a group R4-N-R5, where R4 is a hydrogen atom or a C1-3-alkyl group and R5 is a hydrogen atom or a C1-3-alkyl group, an aminocarbonyl-C1-3-alkyl, C1-3-alkylaminocarbonyl-C1-3-alkyl, di-(C1-3-alkyl)-aminocarbonyl-C1-3-alkyl, pyrrolidin-1-ylcarbonyl-C1-3-alkyl, piperidin-1-ylcarbonyl-C1-3-alkyl, piperazin-1-ylcarbonyl-C1-3-alkyl, 4-C1-3-alkylpiperazin-1-ylcarbonyl-C1-3-alkyl or morpholin-4-ylcarbonyl-C1-3-alkyl group, a hydroxy-C2-4-alkyl, C1-3-alkyloxy-C2-4-alkyl, C1-4-alkyloxycarbonylamino-C2-alkyl, amino-C2-4-alkyl, C1-3-alkylamino-C2-4-alkyl, di-(C1-3-alkyl)amino-C2-4-alkyl, C1-3-alkylcarbonylamino-C2-4-alkyl, aminocarbonylamino-C2-4-alkyl, C1-3-alkyl-aminocarbonylamino-C2-4-alkyl, di-(C1-3-alkyl)aminocarbonylamino-C2-4-alkyl, morpholin-4-ylcarbonylamino-C2-4-alkyl, C1-3-alkylsulphonyl-C2-4-alkyl or C1-3-alkylsulphonylamino-C2-4-alkyl group, a (2-oxopyrrolidin-1-yl)-C2-4-alkyl, (2-oxopiperidin-1-yl)-C2-4-alkyl, (3-oxo-morpholin-4-yl)-C2-4-alkyl, (2-oxoimidazolidin-1-yl)-C2-4-alkyl, (2-oxo-3-methyl-imidazolidin-1-yl)-C2-4-alkyl, (2-oxohexahydropyrimidin-1-yl)-C2-4-alkyl or (2-oxo-
3-methylhexahydropyrimidin-1-yl)-C2-4-alkyl group, a C1-3-alkylsulphonyl, chloro-C2-4-alkylsulphonyl, bromo-C2-4-alkylsulphonyl, amino-C2-4-alkylsulphonyl, C1-3-alkylamino-C2-4-alkylsulphonyl, di-(C1-3-alkyl)-amino-C2-4-alkylsulphonyl, (pyrrolidin-1-yl)-C2-4-alkylsulphonyl, (piperidin-1-yl)-C2-4-alkylsulphonyl or (morpholin-4-yl)-C2-4-alkylsulphonyl group, a C1-4-alkyloxycarbonyl group, a formyl, C1-3-alkylcarbonyl, C1-3-alkyloxy-C1-3-alkylcarbonyl, tetrahydrofuranyl-carbonyl, tetrahydropyranylcarbonyl, amino-C1-3-alkylcarbonyl, C1-3-alkylamino-C1-3-alkylcarbonyl, di-(C1-3-alkyl)amino-C1-3-alkylcarbonyl, pyrrolidin-1-yl-C1-3-alkylcarbonyl, piperidin-1-yl-C1-3-alkylcarbonyl, piperazin-1-yl-C1-3-alkyl-carbonyl, 4-C1-3-alkylpiperazin-1-yl-C1-3-alkylcarbonyl, morpholin-4-yl-C1-3-alkyl-carbonyl or a C1-3-alkylsulphonyl-C1-3-alkylcarbonyl group, a cyano, aminocarbonyl, C1-3-alkylaminocarbonyl, di-(C1-3-alkyl)aminocarbonyl, (C1-3-alkyloxy-C2-4-alkyl)aminocarbonyl, N-(C1-3-alkyl)-N-(C1-3-alkyloxy-C2-4-alkyl)-aminocarbonyl, phenylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-yl-carbonyl, morpholin-4-ylcarbonyl, C1-3-alkylmorpholin-4-ylcarbonyl, di-(C1-3-alkyl)morpholin-4-ylcarbonyl, homomorpholin-4-ylcarbonyl, 2-oxa-5-azabicyclo-[2.2.1 ]hept-5-ylcarbonyl, 3-oxa-8-azabicyclo[3.2.1 ]oct-8-ylcarbonyl, 8-oxa-3-aza-bicyclo[3.2.1]oct-3-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C1-3-alkyl)-piperazin-1-ylcarbonyl, aminosulphonyl, C1-3-alkylaminosulphonyl, di-(C1-3-alkyl)amino-sulphonyl, pyrrolidin-1-yl-sulphonyl, piperidin-1-ylsulphonyl or a morpholin-4-ylsulphonyl group, or a cyclopentyl group, which is substituted in the 3-position by a group R6, where R6 is a 2-oxopyrrolidin-1-yl, 2-oxopiperidin-1-yl, 3-oxomorpholin-4-yl, 2-oxo-imidazolidin-1-yl, 2-oxo-3-methylimidazolidin-1-yl, 2-oxohexahydropyrimidin-1-yl or a 2-oxo-3-methylhexahydropyrimidin-1-yl group, a cyclohexyl group, which is substituted in the 3-position or in the 4-position by a group R4-N-R5, where R4 and R5 are defined as mentioned above, a cyclohexyl group, which is substituted in the 3-position or in the 4-position by a group R6, where R6 is defined as mentioned above, a pyrrolidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a piperidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a piperidin-4-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, or a tetrahydrofuran-3-yl, tetrahydropyran-3-yl or tetrahydropyran-4-yl group, R d is a hydrogen atom, a C1-3-alkyloxy group, a methoxy group, which is substituted by one to three fluorine atoms, an ethyloxy group, which is substituted in the 2-position by a group R6 or R7, where R6 is defined as mentioned above and R7 is a hydroxyl, C1-3-alkyloxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)amino, bis(2-methoxyethyl)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, homomorpholin-4-yl, 2-oxa-5-azabicyclo[2.2.1]hept-5-yl, 3-oxa-8-azabicyclo-[3.2.1]oct-8-yl, 8-oxa-3-azabicyclo[3.2.1]oct-3-yl, piperazin-1-yl or a
4-C1-3-alkylpiperazin-1-yl group, or a formylamino, C1-4-alkylcarbonylamino, C1-3-alkyloxy-C1-3-alkylcarbonylamino, C1-4-alkyloxycarbonylamino, aminocarbonylamino, C1-3-alkylaminocarbonylamino, di-(C1-3-alkyl)aminocarbonylamino, pyrrolidin-1-ylcarbonylamino, piperidin-1-ylcarbonylamino, piperazin-1-ylcarbonylamino, 4-C1-3-alkylpiperazin-1-ylcarbonylamino, morpholin-4-ylcarbonylamino or a C1-4-alkylsulphonylamino group, a propyloxy group, which is substituted in the 3-position by a group R6 or R7, where R6 and R7 are defined as mentioned above, or a butyloxy group, which is substituted in the 4-position by a group R6 or R7, where R6 and R7 are defined as mentioned above, and X is a nitrogen atom, where, if not mentioned otherwise, the abovementioned alkyl groups can be straight-chain or branched, their tautomers, their stereoisomers, their mixtures and their salts.
3. Bicyclic heterocycles of the general formula I according to Claim 1, in which R a is a hydrogen atom, R b is a 1-phenylethyl group, R c is a cyclohexyl group, which is substituted in the 3-position or in the 4-position by a group R4-N-R5, where R4 is a hydrogen atom, a methyl or ethyl group and R5 is a hydrogen atom, a methyl, aminocarbonylmethyl, methylamino-carbonylmethyl, dimethylaminocarbonylmethyl, pyrrolidin-1-ylcarbonylmethyl, piperidin-1-ylcarbonylmethyl, piperazin-1-ylcarbonylmethyl, 4-methylpiperazin-ylcarbonylmethyl, morpholin-4-ylcarbonylmethyl, 2-(morpholin-4-yl-carbonyl)ethyl or 3-(morpholin-4-yl-carbonyl)propyl group, an ethyl, propyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, 3-methoxy-propyl, 2-(butyloxycarbonylamino)ethyl, 2-aminoethyl, 3-aminopropyl, 2-(acetyl-amino)ethyl, 3-(acetylamino)propyl, 2-(ethylcarbonylamino)ethyl, 3-(ethyl-carbonylamino)propyl, 2-(propylcarbonylamino)ethyl, 3-(propylcarbonylamino)-propyl, 2-(ethylaminocarbonylamino)ethyl, 3-(ethylaminocarbonylamino)propyl, 2-(dimethylaminocarbonylamino)ethyl, 3-(dimethylaminocarbonylamino)propyl, 2-(morpholin-4-ylcarbonylamino)ethyl, 3-(morpholin-4-ylcarbonylamino)propyl, 2-(methylsulphonyl)ethyl, 3-(methylsulphonyl)propyl, 2-(methylsulphonylamino)-ethyl or a 3-(methylsulphonylamino)propyl group, a 2-(2-oxopyrrolidin-1-yl)ethyl, 2-(2-oxopiperidin-1-yl)ethyl, 2-(3-oxomorpholin-4-yl)ethyl, 2-(2-oxoimidazolidin-1-yl)ethyl, 2-(2-oxo-3-methylimidazolidin-1-yl)ethyl, 2-(2-oxohexahydropyrimidin-1-yl)ethyl or a 2-(2-oxo-3-methylhexahydropyrimidin-1-yl)ethyl group, a 3-(2-oxopyrrolidin-1-yl)propyl, 3-(2-oxopiperidin-1-yl)propyl, 3-(3-oxomorpholin-4-yl)propyl, 3-(2-oxoimidazolidin-1-yl)propyl, 3-(2-oxo-3-methylimidazolidin-1-yl)propyl, 3-(2-oxohexahydropyrimidin-1-yl)propyl or a 3-(2-oxo-3-methyl-hexahydropyrimidin-1-yl)propyl group, a methylsulphonyl, ethylsulphonyl, 3-chloropropylsulphonyl, 2-(morpholin-4-yl)-ethylsulphonyl or a 3-(morpholin-4-yl)-propylsulphonyl group, a propyloxycarbonyl or butyloxycarbonyl group, a formyl, acetyl, ethylcarbonyl, propylcarbonyl, methoxyacetyl, (2-methoxy-ethyl)carbonyl, (3-methoxypropyl)carbonyl, tetrahydrofuran-2-ylcarbonyl, tetrahydropyran-4-ylcarbonyl, aminoacetyl, methylaminoacetyl, dimethylamino-acetyl, morpholin-4-ylacetyl, [2-(morpholin-4-yl)ethyl]carbonyl, [3-(morpholin-yl)propyl]carbonyl or a methylsulphonylacetyl group, a cyano, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, ethyl-aminocarbonyl, diethylaminocarbonyl, propylaminocarbonyl, (2-methoxyethyl)-aminocarbonyl, N-methyl-N-(2-methoxyethyl)aminocarbonyl, (3-methoxypropyl)-aminocarbonyl, N-methyl-N-(3-methoxypropyl)aminocarbonyl, phenylamino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, 2-methylmorpholin-4-ylcarbonyl, 2,6-dimethylmorpholin-4-ylcarbonyl, homo-morpholin-4-ylcarbonyl, 2-oxa-5-azabicyclo[2.2.1]hept-5-ylcarbonyl, 3-oxa-8-azabicyclo[3.2.1]oct-8-ylcarbonyl, 8-oxa-3-azabicyclo[3.2.1]oct-3-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, aminosulphonyl, methylaminosulphonyl, dimethylaminosulphonyl or a morpholin-4-ylsulphonyl group, a cyclohexyl group, which is substituted in the 3-position or in the 4-position by a group R6, where R6 is a 2-oxopyrrolidin-1-yl, 2-oxopiperidin-1-yl, 3-oxomorpholin-4-yl, 2-oxo-imidazolidin-1-yl, 2-oxo-3-methylimidazolidin-1-yl, 2-oxohexahydropyrimidin-1-yl or a 2-oxo-3-methylhexahydropyrimidin-1-yl group, a pyrrolidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a piperidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a piperidin-4-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl or tetrahydropyran-4-yl group, R d is a hydrogen atom, a methoxy, difluoromethoxy or ethyloxy group, an ethyloxy group, which is substituted in the 2-position by a group R6 or R7, where R6 _55_ is defined as mentioned above and R7 is a hydroxyl, methoxy, ethoxy, amino, dimethylamino, diethylamino, bis(2-methoxyethyl)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, homo-morpholin-4-yl, 2-oxa-5-azabicyclo[2.2.1]hept-5-yl, 3-oxa-8-azabicyclo[3.2.1]oct-8-yl, 8-oxa-3-azabicyclo[3.2.1]oct-3-yl, piperazin-1-yl, 4-methylpiperazin-1-yl or 4-ethylpiperazin-1-yl group, or an acetylamino, ethylcarbonylamino, propylcarbonylamino, butylcarbonylamino, methoxyacetylamino, butyloxycarbonylamino, ethylaminocarbonylamino, dimethylaminocarbonylamino, pyrrolidin-1-ylcarbonylamino, piperidin-1-yl-carbonylamino, morpholin-4-ylcarbonylamino, methylsulphonylamino, ethyl-sulphonylamino or butylsulphonylamino group, a propyloxy group, which is substituted in the 3-position by a group R6 or R7, where R6 and R7 are defined as mentioned above, or a butyloxy group, which is substituted in the 4-position by a group R6 or R7, where R6 and R7 are defined as mentioned above, and X is a nitrogen atom, where, if not mentioned otherwise, the abovementioned alkyl groups can be straight-chain or branched, their tautomers, their stereoisomers, their mixtures and their salts.
4. Bicyclic heterocycles of the general formula I according to Claim 1, in which R a is a hydrogen atom, R b is a 1-phenylethyl group, R c is a cyclohexyl group, which is substituted in the 4-position by an amino, methylamino, dimethylamino, acetylamino, N-(acetyl)methylamino, methoxy-acetylamino, N-(methoxyacetyl)methylamino, tetrahydropyran-4-ylcarbonylamino, N-(tetrahydropyran-4-ylcarbonyl)methylamino, tert-butyloxycarbonylamino, N-(tert-butyloxycarbonyl)methylamino, N-(ethylaminocarbonyl)methylamino, dimethylamino-carbonylamino, N-(dimethylaminocarbonyl)methylamino, N-(piperidin-1-ylcarbonyl)-methylamino, morpholin-4-ylcarbonylamino, N-(morpholin-4-ylcarbonyl)methylamino, N-(4-methylpiperazin-1-ylcarbonyl)methylamino, methylsulphonylamino, N-(methyl-sulphonyl)methylamino, ethylsulphonylamino, N-(ethylsulphonyl)methylamino, dimethyl-aminosulphonylamino, N-(dimethylaminosulphonyl)methylamino, morpholin-4-yl-sulphonylamino or N-(morpholin-4-ylsulphonyl)methylamino group, a pyrrolidin-3-yl group, a pyrrolidin-3-yl group, which is substituted in the 1-position by a tert-butyloxycarbonyl or methylsulphonyl group, a piperidin-3-yl group, a piperidin-3-yl group, which is substituted in the 1-position by a tert-butyloxycarbonyl or methylsulphonyl group, a piperidin-4-yl group, a piperidin-4-yl group, which is substituted in the 1-position by a methyl, (aminocarbonyl)methyl, (dimethylaminocarbonyl)methyl, (morpholin-4-ylcarbonyl)-methyl, 2-(tert-butyloxycarbonylamino)ethyl, 2-aminoethyl, 2-(acetylamino)ethyl, 2-(methylsulphonylamino)ethyl, cyano, acetyl, methoxyacetyl, (dimethylamino)acetyl, (morpholin-4-yl)acetyl, tetrahydropyran-4-ylcarbonyl, ethylaminocarbonyl, isopropyl-aminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, 2-methylmorpholin-4-ylcarbonyl, 2,6-di-methylmorpholin-4-ylcarbonyl, homomorpholin-4-ylcarbonyl, 4-methylpiperazin-1-yl-carbonyl, isopropyloxycarbonyl, tert-butyloxycarbonyl, methylsulphonyl, dimethylamino-sulphonyl or morpholin-4-ylsulphonyl group, or a tetrahydrofuran-3-yl, tetrahydropyran-3-yl or tetrahydropyran-4-yl group, R d is a methoxy, ethyloxy or a 2-(methoxy)ethyloxy group, and X is a nitrogen atom, their tautomers, their stereoisomers, their mixtures and their salts.
3. Bicyclic heterocycles of the general formula I according to Claim 1, in which R a is a hydrogen atom, R b is a 1-phenylethyl group, R c is a cyclohexyl group, which is substituted in the 3-position or in the 4-position by a group R4-N-R5, where R4 is a hydrogen atom, a methyl or ethyl group and R5 is a hydrogen atom, a methyl, aminocarbonylmethyl, methylamino-carbonylmethyl, dimethylaminocarbonylmethyl, pyrrolidin-1-ylcarbonylmethyl, piperidin-1-ylcarbonylmethyl, piperazin-1-ylcarbonylmethyl, 4-methylpiperazin-ylcarbonylmethyl, morpholin-4-ylcarbonylmethyl, 2-(morpholin-4-yl-carbonyl)ethyl or 3-(morpholin-4-yl-carbonyl)propyl group, an ethyl, propyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, 3-methoxy-propyl, 2-(butyloxycarbonylamino)ethyl, 2-aminoethyl, 3-aminopropyl, 2-(acetyl-amino)ethyl, 3-(acetylamino)propyl, 2-(ethylcarbonylamino)ethyl, 3-(ethyl-carbonylamino)propyl, 2-(propylcarbonylamino)ethyl, 3-(propylcarbonylamino)-propyl, 2-(ethylaminocarbonylamino)ethyl, 3-(ethylaminocarbonylamino)propyl, 2-(dimethylaminocarbonylamino)ethyl, 3-(dimethylaminocarbonylamino)propyl, 2-(morpholin-4-ylcarbonylamino)ethyl, 3-(morpholin-4-ylcarbonylamino)propyl, 2-(methylsulphonyl)ethyl, 3-(methylsulphonyl)propyl, 2-(methylsulphonylamino)-ethyl or a 3-(methylsulphonylamino)propyl group, a 2-(2-oxopyrrolidin-1-yl)ethyl, 2-(2-oxopiperidin-1-yl)ethyl, 2-(3-oxomorpholin-4-yl)ethyl, 2-(2-oxoimidazolidin-1-yl)ethyl, 2-(2-oxo-3-methylimidazolidin-1-yl)ethyl, 2-(2-oxohexahydropyrimidin-1-yl)ethyl or a 2-(2-oxo-3-methylhexahydropyrimidin-1-yl)ethyl group, a 3-(2-oxopyrrolidin-1-yl)propyl, 3-(2-oxopiperidin-1-yl)propyl, 3-(3-oxomorpholin-4-yl)propyl, 3-(2-oxoimidazolidin-1-yl)propyl, 3-(2-oxo-3-methylimidazolidin-1-yl)propyl, 3-(2-oxohexahydropyrimidin-1-yl)propyl or a 3-(2-oxo-3-methyl-hexahydropyrimidin-1-yl)propyl group, a methylsulphonyl, ethylsulphonyl, 3-chloropropylsulphonyl, 2-(morpholin-4-yl)-ethylsulphonyl or a 3-(morpholin-4-yl)-propylsulphonyl group, a propyloxycarbonyl or butyloxycarbonyl group, a formyl, acetyl, ethylcarbonyl, propylcarbonyl, methoxyacetyl, (2-methoxy-ethyl)carbonyl, (3-methoxypropyl)carbonyl, tetrahydrofuran-2-ylcarbonyl, tetrahydropyran-4-ylcarbonyl, aminoacetyl, methylaminoacetyl, dimethylamino-acetyl, morpholin-4-ylacetyl, [2-(morpholin-4-yl)ethyl]carbonyl, [3-(morpholin-yl)propyl]carbonyl or a methylsulphonylacetyl group, a cyano, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, ethyl-aminocarbonyl, diethylaminocarbonyl, propylaminocarbonyl, (2-methoxyethyl)-aminocarbonyl, N-methyl-N-(2-methoxyethyl)aminocarbonyl, (3-methoxypropyl)-aminocarbonyl, N-methyl-N-(3-methoxypropyl)aminocarbonyl, phenylamino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, 2-methylmorpholin-4-ylcarbonyl, 2,6-dimethylmorpholin-4-ylcarbonyl, homo-morpholin-4-ylcarbonyl, 2-oxa-5-azabicyclo[2.2.1]hept-5-ylcarbonyl, 3-oxa-8-azabicyclo[3.2.1]oct-8-ylcarbonyl, 8-oxa-3-azabicyclo[3.2.1]oct-3-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, aminosulphonyl, methylaminosulphonyl, dimethylaminosulphonyl or a morpholin-4-ylsulphonyl group, a cyclohexyl group, which is substituted in the 3-position or in the 4-position by a group R6, where R6 is a 2-oxopyrrolidin-1-yl, 2-oxopiperidin-1-yl, 3-oxomorpholin-4-yl, 2-oxo-imidazolidin-1-yl, 2-oxo-3-methylimidazolidin-1-yl, 2-oxohexahydropyrimidin-1-yl or a 2-oxo-3-methylhexahydropyrimidin-1-yl group, a pyrrolidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a piperidin-3-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a piperidin-4-yl group, which is substituted in the 1-position by the group R5, where R5 is defined as mentioned above, a tetrahydrofuran-3-yl, tetrahydropyran-3-yl or tetrahydropyran-4-yl group, R d is a hydrogen atom, a methoxy, difluoromethoxy or ethyloxy group, an ethyloxy group, which is substituted in the 2-position by a group R6 or R7, where R6 _55_ is defined as mentioned above and R7 is a hydroxyl, methoxy, ethoxy, amino, dimethylamino, diethylamino, bis(2-methoxyethyl)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, homo-morpholin-4-yl, 2-oxa-5-azabicyclo[2.2.1]hept-5-yl, 3-oxa-8-azabicyclo[3.2.1]oct-8-yl, 8-oxa-3-azabicyclo[3.2.1]oct-3-yl, piperazin-1-yl, 4-methylpiperazin-1-yl or 4-ethylpiperazin-1-yl group, or an acetylamino, ethylcarbonylamino, propylcarbonylamino, butylcarbonylamino, methoxyacetylamino, butyloxycarbonylamino, ethylaminocarbonylamino, dimethylaminocarbonylamino, pyrrolidin-1-ylcarbonylamino, piperidin-1-yl-carbonylamino, morpholin-4-ylcarbonylamino, methylsulphonylamino, ethyl-sulphonylamino or butylsulphonylamino group, a propyloxy group, which is substituted in the 3-position by a group R6 or R7, where R6 and R7 are defined as mentioned above, or a butyloxy group, which is substituted in the 4-position by a group R6 or R7, where R6 and R7 are defined as mentioned above, and X is a nitrogen atom, where, if not mentioned otherwise, the abovementioned alkyl groups can be straight-chain or branched, their tautomers, their stereoisomers, their mixtures and their salts.
4. Bicyclic heterocycles of the general formula I according to Claim 1, in which R a is a hydrogen atom, R b is a 1-phenylethyl group, R c is a cyclohexyl group, which is substituted in the 4-position by an amino, methylamino, dimethylamino, acetylamino, N-(acetyl)methylamino, methoxy-acetylamino, N-(methoxyacetyl)methylamino, tetrahydropyran-4-ylcarbonylamino, N-(tetrahydropyran-4-ylcarbonyl)methylamino, tert-butyloxycarbonylamino, N-(tert-butyloxycarbonyl)methylamino, N-(ethylaminocarbonyl)methylamino, dimethylamino-carbonylamino, N-(dimethylaminocarbonyl)methylamino, N-(piperidin-1-ylcarbonyl)-methylamino, morpholin-4-ylcarbonylamino, N-(morpholin-4-ylcarbonyl)methylamino, N-(4-methylpiperazin-1-ylcarbonyl)methylamino, methylsulphonylamino, N-(methyl-sulphonyl)methylamino, ethylsulphonylamino, N-(ethylsulphonyl)methylamino, dimethyl-aminosulphonylamino, N-(dimethylaminosulphonyl)methylamino, morpholin-4-yl-sulphonylamino or N-(morpholin-4-ylsulphonyl)methylamino group, a pyrrolidin-3-yl group, a pyrrolidin-3-yl group, which is substituted in the 1-position by a tert-butyloxycarbonyl or methylsulphonyl group, a piperidin-3-yl group, a piperidin-3-yl group, which is substituted in the 1-position by a tert-butyloxycarbonyl or methylsulphonyl group, a piperidin-4-yl group, a piperidin-4-yl group, which is substituted in the 1-position by a methyl, (aminocarbonyl)methyl, (dimethylaminocarbonyl)methyl, (morpholin-4-ylcarbonyl)-methyl, 2-(tert-butyloxycarbonylamino)ethyl, 2-aminoethyl, 2-(acetylamino)ethyl, 2-(methylsulphonylamino)ethyl, cyano, acetyl, methoxyacetyl, (dimethylamino)acetyl, (morpholin-4-yl)acetyl, tetrahydropyran-4-ylcarbonyl, ethylaminocarbonyl, isopropyl-aminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, 2-methylmorpholin-4-ylcarbonyl, 2,6-di-methylmorpholin-4-ylcarbonyl, homomorpholin-4-ylcarbonyl, 4-methylpiperazin-1-yl-carbonyl, isopropyloxycarbonyl, tert-butyloxycarbonyl, methylsulphonyl, dimethylamino-sulphonyl or morpholin-4-ylsulphonyl group, or a tetrahydrofuran-3-yl, tetrahydropyran-3-yl or tetrahydropyran-4-yl group, R d is a methoxy, ethyloxy or a 2-(methoxy)ethyloxy group, and X is a nitrogen atom, their tautomers, their stereoisomers, their mixtures and their salts.
5. Bicyclic heterocycles of the general formula I according to Claim 1, in which R a is a hydrogen atom, R b is a 1-phenylethyl group, R c is a piperidin-4-yl group, a piperidin-4-yl group, which is substituted in the 1-position by a methyl, cyano, acetyl, morpholin-4-ylcarbonyl, tert-butyloxycarbonyl or methylsulphonyl group, R d is a methoxy group and X is a nitrogen atom, their tautomers, their stereoisomers, their mixtures and their salts.
6. Physiologically tolerable salts of the compounds according to at least one of Claims 1 to 5 with inorganic or organic acids or bases.
7. Medicaments comprising a compound according to at least one of Claims 1 to 5 or a physiologically tolerable salt according to Claim 6 in addition, if appropriate, to one or more inert vehicles and/or diluents.
8. Use of a compound according to at least one of Claims 1 to 6 for the preparation of a medicament which is suitable for the treatment of benign or malignant tumours, for the prevention and treatment of diseases of the airways and of the lung and for the treatment of diseases of the gastrointestinal tract and of the bile ducts and gall bladder.
9. Process for the preparation of a medicament according to Claim 7, characterized in that, by non-chemical means, a compound according to at least one of Claims 1 to 6 is incorporated into one or more inert vehicles and/or diluents.
10. Process for the preparation of the compounds of the general formula I
according to Claims 1 to 5, characterized in that a) a compound of the general formula in which R a, R b, R d and X are defined as mentioned in Claims 1 to 6, is reacted with a compound of the general formula Z1 - R c (III) in which R c is defined as mentioned in Claims 1 to 6 and Z1 is a leaving group, or b) for the preparation of compounds of the general formula I, in which R d is one of the optionally substituted alkyloxy groups mentioned in Claims 1 to 6, a compound of the general formula in which R a, R b, R c and X are defined as mentioned in Claims 1 to 6, is reacted with a compound of the general formula Z2 - R d' (V) in which R d' is a C1-4-alkyl group, a methyl group substituted by 1 to 3 fluorine atoms, an ethyl group substituted by 1 to 5 fluorine atoms, a C2-4-alkyl group substituted by a group R6 or R7, where R6 and R7 are defined as mentioned in Claims 1 to 6, a C1-4-alkyl group, which is substituted by a pyrrolidinyl, piperidinyl or homopiperidinyl group substituted in the 1-position by the group R8, or a C1-4-alkyl group, which is substituted by a morpholinyl group substituted in the 4-position by the group R8, where R8 is in each case defined as mentioned in Claims 1 to 6, and Z2 is a leaving group, or c) for the preparation of compounds of the general formula I, in which R d is one of the alkyloxy groups mentioned in Claims 1 to 6, which is substituted by an optionally substituted amino, alkylamino or dialkylamino group or by an optionally substituted heterocyclic group bonded via an imino nitrogen atom, a compound of the general formula in which R a, R b, R c and X are defined as mentioned in Claims 1 to 6 and Z3 is a leaving group, is reacted with ammonia, an appropriate, optionally substituted alkylamine, dialkylamine or an imino compound or their suitable salts or derivatives or d) for the preparation of compounds of the general formula I, in which R d is a hydroxyl group, a protective group is cleaved from a compound of the general formula n which R a, R b, R c and X are defined as mentioned in Claims 1 to 6 and R d"
is a group which can be converted into a hydroxyl group, or e) for the preparation of compounds of the general formula I, in which R c contains an -NH group, a protective group is cleaved from a compound of the general formula in which R a, R b, R d and X are defined as mentioned in Claims 1 to 6 and R
c' has the meanings mentioned for R c in Claims 1 to 6 with the proviso that R c contains a protected nitrogen atom, or f) for the preparation of compounds of the general formula I, in which R c contains an alkyl group substituted by an optionally substituted amino, alkylamino or dialkyamino group or by an optionally substituted heterocyclic group bonded via a nitrogen atom, a compound of the general formula in which R a, R b, R d and X are defined as mentioned in Claims 1 to 6, Z3 is a leaving group and R c" has the meanings mentioned for R c in Claims 1 to 6 with the proviso that a hydrogen atom bonded to an aliphatic carbon atom is replaced by the group Z3, is reacted with ammonia, an appropriate, optionally substituted alkylamine, dialkylamine or an imino compound or their suitable salts or derivatives and if desired a compound of the general formula I thus obtained, which contains an amino, alkylamino or imino group, is converted by means of acylation, cyanation or sulphonylation into a corresponding acyl, cyano or sulphonyl compound of the general formula I and/or a compound of the general formula I thus obtained, which contains an amino, alkylamino or imino group, is converted by means of alkylation or reductive alkylation into a corresponding alkyl compound of the general formula I and/or a compound of the general formula I thus obtained, which contains a chloro-C1-4-alkylsulphonyl or a bromo-C1-4-alkylsulphonyl group, is converted by means of reaction with an amine into a corresponding amino-C1-4-alkylsulphonyl compound and/or a compound of the general formula I thus obtained, which contains a tert-butyloxycarbonylamino, N-alkyl-N-(tert-butyloxycarbonyl)amino or an N-tert-butyloxycarbonylimino group, is converted by means of treatment with an acid into a corresponding amino, alkylamino or imino compound of the general formula I, and/or if necessary a protective group used in the reactions described above is cleaved again and/or if desired a compound of the general formula I thus obtained is separated into its stereoisomers and/or a compound of the general formula I thus obtained is converted into its salts, in particular for pharmaceutical administration into its physiologically tolerable salts.
according to Claims 1 to 5, characterized in that a) a compound of the general formula in which R a, R b, R d and X are defined as mentioned in Claims 1 to 6, is reacted with a compound of the general formula Z1 - R c (III) in which R c is defined as mentioned in Claims 1 to 6 and Z1 is a leaving group, or b) for the preparation of compounds of the general formula I, in which R d is one of the optionally substituted alkyloxy groups mentioned in Claims 1 to 6, a compound of the general formula in which R a, R b, R c and X are defined as mentioned in Claims 1 to 6, is reacted with a compound of the general formula Z2 - R d' (V) in which R d' is a C1-4-alkyl group, a methyl group substituted by 1 to 3 fluorine atoms, an ethyl group substituted by 1 to 5 fluorine atoms, a C2-4-alkyl group substituted by a group R6 or R7, where R6 and R7 are defined as mentioned in Claims 1 to 6, a C1-4-alkyl group, which is substituted by a pyrrolidinyl, piperidinyl or homopiperidinyl group substituted in the 1-position by the group R8, or a C1-4-alkyl group, which is substituted by a morpholinyl group substituted in the 4-position by the group R8, where R8 is in each case defined as mentioned in Claims 1 to 6, and Z2 is a leaving group, or c) for the preparation of compounds of the general formula I, in which R d is one of the alkyloxy groups mentioned in Claims 1 to 6, which is substituted by an optionally substituted amino, alkylamino or dialkylamino group or by an optionally substituted heterocyclic group bonded via an imino nitrogen atom, a compound of the general formula in which R a, R b, R c and X are defined as mentioned in Claims 1 to 6 and Z3 is a leaving group, is reacted with ammonia, an appropriate, optionally substituted alkylamine, dialkylamine or an imino compound or their suitable salts or derivatives or d) for the preparation of compounds of the general formula I, in which R d is a hydroxyl group, a protective group is cleaved from a compound of the general formula n which R a, R b, R c and X are defined as mentioned in Claims 1 to 6 and R d"
is a group which can be converted into a hydroxyl group, or e) for the preparation of compounds of the general formula I, in which R c contains an -NH group, a protective group is cleaved from a compound of the general formula in which R a, R b, R d and X are defined as mentioned in Claims 1 to 6 and R
c' has the meanings mentioned for R c in Claims 1 to 6 with the proviso that R c contains a protected nitrogen atom, or f) for the preparation of compounds of the general formula I, in which R c contains an alkyl group substituted by an optionally substituted amino, alkylamino or dialkyamino group or by an optionally substituted heterocyclic group bonded via a nitrogen atom, a compound of the general formula in which R a, R b, R d and X are defined as mentioned in Claims 1 to 6, Z3 is a leaving group and R c" has the meanings mentioned for R c in Claims 1 to 6 with the proviso that a hydrogen atom bonded to an aliphatic carbon atom is replaced by the group Z3, is reacted with ammonia, an appropriate, optionally substituted alkylamine, dialkylamine or an imino compound or their suitable salts or derivatives and if desired a compound of the general formula I thus obtained, which contains an amino, alkylamino or imino group, is converted by means of acylation, cyanation or sulphonylation into a corresponding acyl, cyano or sulphonyl compound of the general formula I and/or a compound of the general formula I thus obtained, which contains an amino, alkylamino or imino group, is converted by means of alkylation or reductive alkylation into a corresponding alkyl compound of the general formula I and/or a compound of the general formula I thus obtained, which contains a chloro-C1-4-alkylsulphonyl or a bromo-C1-4-alkylsulphonyl group, is converted by means of reaction with an amine into a corresponding amino-C1-4-alkylsulphonyl compound and/or a compound of the general formula I thus obtained, which contains a tert-butyloxycarbonylamino, N-alkyl-N-(tert-butyloxycarbonyl)amino or an N-tert-butyloxycarbonylimino group, is converted by means of treatment with an acid into a corresponding amino, alkylamino or imino compound of the general formula I, and/or if necessary a protective group used in the reactions described above is cleaved again and/or if desired a compound of the general formula I thus obtained is separated into its stereoisomers and/or a compound of the general formula I thus obtained is converted into its salts, in particular for pharmaceutical administration into its physiologically tolerable salts.
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| DEDE10345875.1 | 2003-09-30 | ||
| DE10345875A DE10345875A1 (en) | 2003-09-30 | 2003-09-30 | Bicyclic heterocycles, pharmaceutical compositions containing them, their use and methods of preparation |
| PCT/EP2004/010723 WO2005033096A1 (en) | 2003-09-30 | 2004-09-24 | Quinoline derivatives and quinazoline derivatives, medicaments containing said compounds, use thereof, and method for the production thereof |
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| EP (1) | EP1670781A1 (en) |
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| PT1731511E (en) | 1999-06-21 | 2015-11-13 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and methods for the production thereof |
| US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| JP5688877B2 (en) | 2005-11-11 | 2015-03-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Quinazoline derivatives for the treatment of cancer diseases |
| JPWO2008023720A1 (en) * | 2006-08-23 | 2010-01-14 | アステラス製薬株式会社 | Urea compound or salt thereof |
| SI2068880T1 (en) | 2006-09-18 | 2012-08-31 | Boehringer Ingelheim Int | Method for treating cancer harboring egfr mutations |
| LT2451445T (en) | 2009-07-06 | 2019-06-25 | Boehringer Ingelheim International Gmbh | Process for drying of bibw2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
| KR101317809B1 (en) | 2011-06-07 | 2013-10-16 | 한미약품 주식회사 | Pharmaceutical composition comprising amide derivative inhibiting the growth of cancer cell and non-metalic salt lubricant |
| KR20140096571A (en) | 2013-01-28 | 2014-08-06 | 한미약품 주식회사 | Method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)prop-2-en-1-one |
| US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
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| CA2249446C (en) * | 1996-04-12 | 2008-06-17 | Warner-Lambert Company | Irreversible inhibitors of tyrosine kinases |
| BR0008524A (en) * | 1999-02-27 | 2001-12-18 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for their preparation |
| DE19911509A1 (en) * | 1999-03-15 | 2000-09-21 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| PT1731511E (en) * | 1999-06-21 | 2015-11-13 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and methods for the production thereof |
| AU7425801A (en) * | 2000-06-24 | 2002-01-08 | Astrazeneca Ab | Guanidine derivatives of quinazoline and quinoline for use in the treatment of autoimmune diseases |
| DE10042059A1 (en) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| DE10042058A1 (en) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| US7067532B2 (en) * | 2000-11-02 | 2006-06-27 | Astrazeneca | Substituted quinolines as antitumor agents |
| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| BR0308902A (en) * | 2002-03-30 | 2005-01-04 | Boehringer Ingelheim Pharma | 4- (n-phenylamino) -quinazolines / quinolines as tyrosine kinase inhibitors |
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- 2003-09-30 DE DE10345875A patent/DE10345875A1/en not_active Withdrawn
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2004
- 2004-09-24 WO PCT/EP2004/010723 patent/WO2005033096A1/en active Application Filing
- 2004-09-24 JP JP2006530024A patent/JP2007507445A/en active Pending
- 2004-09-24 EP EP04765571A patent/EP1670781A1/en not_active Withdrawn
- 2004-09-24 CA CA2540501A patent/CA2540501C/en not_active Expired - Fee Related
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| CA2540501C (en) | 2012-05-22 |
| DE10345875A1 (en) | 2005-04-21 |
| EP1670781A1 (en) | 2006-06-21 |
| JP2007507445A (en) | 2007-03-29 |
| WO2005033096A1 (en) | 2005-04-14 |
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