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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- CA2540501A1 CA2540501A1 CA002540501A CA2540501A CA2540501A1 CA 2540501 A1 CA2540501 A1 CA 2540501A1 CA 002540501 A CA002540501 A CA 002540501A CA 2540501 A CA2540501 A CA 2540501A CA 2540501 A1 CA2540501 A1 CA 2540501A1
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- Prior art keywords
- group
- alkyl
- ylcarbonyl
- substituted
- morpholin
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- 150000001875 compounds Chemical class 0.000 title claims 25
- 239000003814 drug Substances 0.000 title claims 4
- 238000000034 method Methods 0.000 title claims 3
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract 13
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract 6
- 239000000203 mixture Substances 0.000 claims abstract 6
- 201000010099 disease Diseases 0.000 claims abstract 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 4
- 210000004072 lung Anatomy 0.000 claims abstract 2
- 150000007522 mineralic acids Chemical class 0.000 claims abstract 2
- 150000007524 organic acids Chemical class 0.000 claims abstract 2
- 235000005985 organic acids Nutrition 0.000 claims abstract 2
- -1 2-oxopyrrolidin-1-yl Chemical group 0.000 claims 241
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 7
- 229910052740 iodine Inorganic materials 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 229910052757 nitrogen Inorganic materials 0.000 claims 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 7
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 7
- 125000001153 fluoro group Chemical group F* 0.000 claims 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 5
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 5
- 125000003282 alkyl amino group Chemical group 0.000 claims 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 5
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 4
- 229910052801 chlorine Inorganic materials 0.000 claims 4
- 239000000460 chlorine Substances 0.000 claims 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 4
- 229910052731 fluorine Inorganic materials 0.000 claims 4
- 239000011737 fluorine Substances 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 3
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 125000002757 morpholinyl group Chemical group 0.000 claims 3
- 125000003386 piperidinyl group Chemical group 0.000 claims 3
- 125000006239 protecting group Chemical group 0.000 claims 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 3
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims 2
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 2
- 125000006599 (C1-C3) alkylaminocarbonylamino group Chemical group 0.000 claims 2
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 2
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims 2
- 150000003973 alkyl amines Chemical class 0.000 claims 2
- 229910021529 ammonia Inorganic materials 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims 2
- 125000005265 dialkylamine group Chemical class 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims 1
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 230000029936 alkylation Effects 0.000 claims 1
- 238000005804 alkylation reaction Methods 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims 1
- 125000005002 aryl methyl group Chemical group 0.000 claims 1
- 125000004104 aryloxy group Chemical group 0.000 claims 1
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 1
- 210000000013 bile duct Anatomy 0.000 claims 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 238000007333 cyanation reaction Methods 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical group N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims 1
- 210000000232 gallbladder Anatomy 0.000 claims 1
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 1
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 1
- 125000004673 propylcarbonyl group Chemical group 0.000 claims 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims 1
- 125000003373 pyrazinyl group Chemical group 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 238000005932 reductive alkylation reaction Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 125000005415 substituted alkoxy group Chemical group 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 abstract 2
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 210000002345 respiratory system Anatomy 0.000 abstract 1
- 230000019491 signal transduction Effects 0.000 abstract 1
Classifications
-
- 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
-
- 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
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
-
- 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
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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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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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US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
CA2833706C (en) | 2005-11-11 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
CA2665804A1 (en) * | 2006-08-23 | 2008-02-28 | Astellas Pharma Inc. | Urea compound or salt thereof |
PT2068880E (en) | 2006-09-18 | 2012-07-12 | 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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AU7425801A (en) * | 2000-06-24 | 2002-01-08 | Astrazeneca Ab | Guanidine derivatives of quinazoline and quinoline for use in the treatment of autoimmune diseases |
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EA200701302A1 (en) * | 2002-03-30 | 2007-12-28 | Бёрингер Ингельхайм Фарма Гмбх Унд Ко. Кг | 4- (N-PHYLENAMINO) QUINAZOLIN / -CHINOLINE AS THYROSINKINASE INHIBITORS |
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