NO330486B1 - 3-z-(1-(4-(n-((4-4metyl-piperazin-1-yl)-metylkarbonyl)-n-metyl-amino)-anilino)-1-fenyl-metylen)-6-metoksykarb onyl-2-indolinon-monoetansulfonat, farmasoytisk preparat med og metbolitt av denne, fremstilling av farmasoytisk preparat og anvendelse av forbindelsen for fremstilling av farmasoytisk preparat for behandling av sykdom - Google Patents
3-z-(1-(4-(n-((4-4metyl-piperazin-1-yl)-metylkarbonyl)-n-metyl-amino)-anilino)-1-fenyl-metylen)-6-metoksykarb onyl-2-indolinon-monoetansulfonat, farmasoytisk preparat med og metbolitt av denne, fremstilling av farmasoytisk preparat og anvendelse av forbindelsen for fremstilling av farmasoytisk preparat for behandling av sykdom Download PDFInfo
- Publication number
- NO330486B1 NO330486B1 NO20050985A NO20050985A NO330486B1 NO 330486 B1 NO330486 B1 NO 330486B1 NO 20050985 A NO20050985 A NO 20050985A NO 20050985 A NO20050985 A NO 20050985A NO 330486 B1 NO330486 B1 NO 330486B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- phenyl
- piperazin
- amino
- methylene
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 17
- 239000002207 metabolite Substances 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title description 11
- 201000010099 disease Diseases 0.000 title description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 title 3
- -1 (4-methyl-piperazin-1-yl) -methylcarbonyl Chemical group 0.000 claims abstract description 24
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 19
- MMMVNAGRWOJNMW-FJBFXRHMSA-N nintedanib esylate Chemical compound CCS(O)(=O)=O.O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 MMMVNAGRWOJNMW-FJBFXRHMSA-N 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 6
- 238000002844 melting Methods 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 238000010586 diagram Methods 0.000 claims description 3
- 238000011156 evaluation Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 3
- KEHNCEDHZGQSNP-DQSJHHFOSA-N (3z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1h-indole-6-carboxylic acid Chemical compound C=1C=C(N\C(=C/2C3=CC=C(C=C3NC\2=O)C(O)=O)C=2C=CC=CC=2)C=CC=1N(C)C(=O)CN1CCN(C)CC1 KEHNCEDHZGQSNP-DQSJHHFOSA-N 0.000 claims description 2
- 238000005259 measurement Methods 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 4
- 239000003085 diluting agent Substances 0.000 claims 4
- 230000002159 abnormal effect Effects 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 239000013543 active substance Substances 0.000 description 17
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical class C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 3
- CPMDPSXJELVGJG-UHFFFAOYSA-N methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate Chemical compound OC=1NC2=CC(=CC=C2C=1C(=NC1=CC=C(C=C1)N(C(CN1CCN(CC1)C)=O)C)C1=CC=CC=C1)C(=O)OC CPMDPSXJELVGJG-UHFFFAOYSA-N 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 2
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 2
- 239000001828 Gelatine Substances 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000006257 n-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])OC(*)=O 0.000 description 2
- 125000006256 n-propyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC(*)=O 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 238000012289 standard assay Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000002076 thermal analysis method Methods 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 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 description 1
- 101100223811 Caenorhabditis elegans dsc-1 gene Proteins 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- 108010051152 Carboxylesterase Proteins 0.000 description 1
- 102000013392 Carboxylesterase Human genes 0.000 description 1
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 1
- 101150026109 INSR gene Proteins 0.000 description 1
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 1
- 101150038994 PDGFRA gene Proteins 0.000 description 1
- 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 1
- 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 150000001602 bicycloalkyls Chemical group 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000000119 electrospray ionisation mass spectrum Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- JKNKNWJNCOJPLI-UHFFFAOYSA-N o-phthalaldehydic acid Chemical compound C1=CC=C2C(O)OC(=O)C2=C1 JKNKNWJNCOJPLI-UHFFFAOYSA-N 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 239000003186 pharmaceutical solution Substances 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002023 wood Substances 0.000 description 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10233500A DE10233500A1 (de) | 2002-07-24 | 2002-07-24 | 3-Z-[1-(4-(N-((4-Methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylen]-6-methoxycarbonyl-2-indolinon-Monoethansulfonat und dessen Verwendung als Arzneimittel |
| PCT/EP2003/007822 WO2004013099A1 (fr) | 2002-07-24 | 2003-07-18 | 3-z-[1-(4-(n-((4-methyl-piperazin-1-yl)-methylcarbonyl)-n-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone-monoethanesulfonate et utilisation en tant que composition pharmaceutique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20050985L NO20050985L (no) | 2005-02-23 |
| NO330486B1 true NO330486B1 (no) | 2011-04-26 |
Family
ID=30469050
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20050985A NO330486B1 (no) | 2002-07-24 | 2005-02-23 | 3-z-(1-(4-(n-((4-4metyl-piperazin-1-yl)-metylkarbonyl)-n-metyl-amino)-anilino)-1-fenyl-metylen)-6-metoksykarb onyl-2-indolinon-monoetansulfonat, farmasoytisk preparat med og metbolitt av denne, fremstilling av farmasoytisk preparat og anvendelse av forbindelsen for fremstilling av farmasoytisk preparat for behandling av sykdom |
Country Status (36)
| Country | Link |
|---|---|
| US (2) | US7119093B2 (fr) |
| EP (2) | EP2386543A1 (fr) |
| JP (1) | JP5039279B2 (fr) |
| KR (1) | KR101145691B1 (fr) |
| CN (1) | CN100351235C (fr) |
| AR (2) | AR040662A1 (fr) |
| AT (1) | ATE551322T1 (fr) |
| AU (1) | AU2003254376B2 (fr) |
| BR (1) | BRPI0312811B8 (fr) |
| CA (1) | CA2493310C (fr) |
| CY (1) | CY1112916T1 (fr) |
| DE (1) | DE10233500A1 (fr) |
| DK (1) | DK1527047T3 (fr) |
| EA (1) | EA008684B1 (fr) |
| EC (1) | ECSP055571A (fr) |
| EG (1) | EG24562A (fr) |
| ES (1) | ES2384968T3 (fr) |
| HK (1) | HK1078851A1 (fr) |
| HR (1) | HRP20050070B1 (fr) |
| IL (2) | IL166405A0 (fr) |
| ME (1) | ME00353B (fr) |
| MX (1) | MXPA04012785A (fr) |
| MY (1) | MY136883A (fr) |
| NO (1) | NO330486B1 (fr) |
| NZ (1) | NZ538367A (fr) |
| PE (1) | PE20040704A1 (fr) |
| PL (1) | PL223758B1 (fr) |
| PT (1) | PT1527047E (fr) |
| RS (1) | RS52283B (fr) |
| SA (1) | SA03240446B1 (fr) |
| SI (1) | SI1527047T1 (fr) |
| TW (1) | TWI285635B (fr) |
| UA (1) | UA78352C2 (fr) |
| UY (1) | UY27904A1 (fr) |
| WO (1) | WO2004013099A1 (fr) |
| ZA (1) | ZA200409814B (fr) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10233500A1 (de) * | 2002-07-24 | 2004-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 3-Z-[1-(4-(N-((4-Methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylen]-6-methoxycarbonyl-2-indolinon-Monoethansulfonat und dessen Verwendung als Arzneimittel |
| US20040204458A1 (en) * | 2002-08-16 | 2004-10-14 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of Lck inhibitors for treatment of immunologic diseases |
| US20050043233A1 (en) | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| PE20060777A1 (es) * | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| WO2007057397A1 (fr) * | 2005-11-15 | 2007-05-24 | Boehringer Ingelheim International Gmbh | Traitement du cancer |
| EP1870400A1 (fr) * | 2006-06-08 | 2007-12-26 | Boehringer Ingelheim Pharma GmbH & Co. KG | Sels et sels cristallines d'un produit 2-indolinone |
| EP2170827B1 (fr) | 2007-06-21 | 2013-08-14 | Janssen Pharmaceutica, N.V. | Indolin-2-ones et aza-indolin-2-ones |
| US8304541B2 (en) * | 2007-12-03 | 2012-11-06 | Boehringer Ingelheim International Gmbh | Process for the manufacture of an indolinone derivative |
| UY31506A1 (es) * | 2007-12-03 | 2009-08-03 | Derivados de indolinona y procedimiento para su preparacion | |
| UA107560C2 (uk) * | 2008-06-06 | 2015-01-26 | Фармацевтична лікарська форма для негайного вивільнення похідної індолінону | |
| ME02273B (me) * | 2008-06-06 | 2016-02-20 | Boehringer Ingelheim Int | Farmaceutska kombinacija |
| PT2299987T (pt) | 2008-06-06 | 2018-05-21 | Boehringer Ingelheim Int | Forma de dosagem farmacêutica em cápsula compreendendo uma formulação de suspensão de um derivado de indolinona |
| US20170065529A1 (en) | 2015-09-09 | 2017-03-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical dosage form for immediate release of an indolinone derivative |
| EP2387401A1 (fr) | 2009-01-14 | 2011-11-23 | Boehringer Ingelheim International GmbH | Méthode de traitement d'un cancer colorectal |
| US8802384B2 (en) * | 2009-03-12 | 2014-08-12 | Boehringer Ingelheim International Gmbh | Method or system using biomarkers for the monitoring of a treatment |
| JP2012526766A (ja) | 2009-05-14 | 2012-11-01 | 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 | 腫瘍性及び線維性疾患の処置における新規な併用療法 |
| WO2010130758A1 (fr) * | 2009-05-14 | 2010-11-18 | Boehringer Ingelheim International Gmbh | Nouvelle thérapie en combinaison dans le traitement du cancer et de maladies fibreuses |
| US20120107304A1 (en) | 2010-04-27 | 2012-05-03 | Boehringer Ingelheim International Gmbh | Combination therapy in treatment of oncological and fibrotic diseases |
| WO2012068441A2 (fr) | 2010-11-19 | 2012-05-24 | Ratiopharm Gmbh | Sels d'intedanib et leurs formes à l'état solide |
| WO2013059740A1 (fr) | 2011-10-21 | 2013-04-25 | Foundation Medicine, Inc. | Nouvelles molécules de fusion alk et ntrk1 et leurs utilisations |
| JP2015524400A (ja) | 2012-07-19 | 2015-08-24 | 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 | ９−［４−（３−クロロ−２−フルオロ−フェニルアミノ）−７−メトキシ−キナゾリン−６−イルオキシ］−１，４−ジアザ−スピロ［５．５］ウンデカン−５−オンのフマル酸塩、その薬物としての使用及び調製 |
| AU2013337264B2 (en) | 2012-11-05 | 2018-03-08 | Foundation Medicine, Inc. | Novel fusion molecules and uses thereof |
| EP2914621B1 (fr) | 2012-11-05 | 2023-06-07 | Foundation Medicine, Inc. | Nouvelles molécules de fusion de ntrk1 et leurs utilisations |
| US10980804B2 (en) | 2013-01-18 | 2021-04-20 | Foundation Medicine, Inc. | Methods of treating cholangiocarcinoma |
| US20140350022A1 (en) * | 2013-05-10 | 2014-11-27 | Boehringer Ingelheim International Gmbh | Efficacious treatment of NSCLC and predictive clinical marker of the responsiveness of a tumour to a treatment |
| CN104003925B (zh) * | 2013-06-05 | 2016-03-30 | 四川大学 | 吲哚酮化合物或其衍生物及其用途 |
| WO2015009889A1 (fr) * | 2013-07-18 | 2015-01-22 | Concert Pharmaceuticals, Inc. | Dérivés deutériés d'intédanib et leur utilisation pour le traitement de troubles prolifératifs |
| US20150044288A1 (en) | 2013-07-31 | 2015-02-12 | Windward Pharma, Inc. | Aerosol tyrosine kinase inhibitor compounds and uses thereof |
| US20170114323A1 (en) * | 2014-06-19 | 2017-04-27 | Whitehead Institute For Biomedical Research | Uses of kinase inhibitors for inducing and maintaining pluripotency |
| CN106008308A (zh) * | 2015-03-13 | 2016-10-12 | 正大天晴药业集团股份有限公司 | 尼达尼布乙磺酸盐结晶 |
| WO2016178064A1 (fr) | 2015-05-06 | 2016-11-10 | Suven Life Sciences Limited | Polymorphe d'éthanesulfonate de nintedanib, procédés et intermédiaires associés |
| CN105126909B (zh) * | 2015-07-13 | 2018-01-23 | 淮海工学院 | 固载钯催化剂在4‑苯乙炔基‑3‑硝基苯甲酸甲酯合成中的应用 |
| CN105001143A (zh) * | 2015-07-24 | 2015-10-28 | 南京正大天晴制药有限公司 | 一种制备高纯度乙磺酸尼达尼布的方法 |
| CN106432042A (zh) * | 2015-08-13 | 2017-02-22 | 南京华威医药科技开发有限公司 | 尼达尼布乙磺酸水合物的药物新晶型 |
| WO2017077551A2 (fr) * | 2015-11-03 | 2017-05-11 | Mylan Laboratories Limited | Esylate nintedanib amorphe et sa dispersion solide |
| CZ2016104A3 (cs) | 2016-02-24 | 2017-09-06 | Zentiva, K.S. | Krystalické modifikace solí methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}fenyl)amino](fenyl)methyliden}-2-oxo-2,3-dihydro-1H-indol-6-karboxylátu a způsoby jejich přípravy |
| WO2017178428A1 (fr) | 2016-04-13 | 2017-10-19 | Boehringer Ingelheim International Gmbh | Combinaison pharmaceutique de nintédanib, de trifluridine et de tipiracil pour le traitement du cancer colorectal |
| EP3246029A1 (fr) | 2016-05-19 | 2017-11-22 | Boehringer Ingelheim International Gmbh | Combinaison pharmaceutique de nintedanib et de capécitabine dans le traitement du cancer colorectal |
| CN109415314A (zh) * | 2016-05-19 | 2019-03-01 | 上海诚妙医药科技有限公司 | 尼达尼布的新晶型及其制备方法及其用途 |
| JP2019522638A (ja) | 2016-05-27 | 2019-08-15 | 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 | ニンテダニブ及びピルフェニドンによる治療開始を判定するためのｅｃｍバイオマーカーの使用 |
| EP3463353A1 (fr) | 2016-06-01 | 2019-04-10 | Boehringer Ingelheim International GmbH | Utilisation de biomarqueurs de matrice extracellulaire pour déterminer le moment d'instauration d'un traitement sous nintédanib et pirfénidone |
| ITUA20164213A1 (it) | 2016-06-08 | 2017-12-08 | Olon Spa | Polimorfo di nintedanib |
| JP7018939B2 (ja) | 2016-09-26 | 2022-02-14 | ルヤン （スーチョウ） バイオロジー サイエンス アンド テクノロジー カンパニー，リミテッド | 眼疾患の治療のための組成物ならびに使用および調製方法 |
| US20200069679A1 (en) | 2016-12-12 | 2020-03-05 | Boehringer Ingelheim International Gmbh | Nintedanib for use in methods for the treatment of interstitial lung diseases by coadministration with oladaterol |
| US10981896B2 (en) * | 2017-03-02 | 2021-04-20 | Board Of Regents, The University Of Texas System | Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase |
| CN110072849A (zh) * | 2017-03-14 | 2019-07-30 | 新源生物科技股份有限公司 | 3-z-[1-(4-(n-((4-甲基-哌嗪-1-基)-甲羰基)-n-甲基-氨基)-苯氨基)-1-苯基-亚甲基]-6-甲氧羰基-2-吲哚满酮的晶型 |
| TWI632133B (zh) * | 2017-03-15 | 2018-08-11 | 新源生物科技股份有限公司 | ３－ｚ－［１－（４－（ｎ－（（４－甲基－哌嗪－１－基）－甲羰基）－ｎ－甲基－胺基）－苯胺基）－１－苯基－亞甲基］－６－甲氧羰基－２－吲哚啉酮的晶型 |
| TWI676617B (zh) * | 2017-03-15 | 2019-11-11 | 新源生物科技股份有限公司 | 3-z-[1-(4-(n-((4-甲基-呱嗪-1-基)-甲羰基)-n-甲基-胺基)-苯胺基)-1-苯基-亞甲基]-6-甲氧羰基-2-吲哚啉酮的晶型 |
| CN110573161A (zh) | 2017-03-28 | 2019-12-13 | 勃林格殷格翰国际有限公司 | 用于治疗肌营养不良的方法的尼达尼布 |
| WO2019048974A1 (fr) * | 2017-09-06 | 2019-03-14 | Glenmark Pharmaceuticals Limited | Procédé de préparation de nintédanib |
| WO2019081235A1 (fr) | 2017-10-23 | 2019-05-02 | Boehringer Ingelheim International Gmbh | Nouvelle association d'agents actifs pour le traitement de pneumopathies interstitielles fibrosantes progressives (pf-ild) |
| WO2019097112A1 (fr) | 2017-11-17 | 2019-05-23 | Fermion Oy | Synthèse d'un dérivé de 2-indolinone appelé intermédiaire pour la préparation de nintédanib |
| PL3761980T3 (pl) | 2018-03-07 | 2024-06-10 | Pliant Therapeutics, Inc. | Związki aminokwasowe i sposoby zastosowania |
| EP3806858A4 (fr) | 2018-06-15 | 2022-03-09 | Handa Pharmaceuticals, Inc. | Sels d'inhibiteurs de kinases et compositions associées |
| CN109988094B (zh) * | 2019-04-29 | 2020-04-14 | 石药集团中奇制药技术（石家庄）有限公司 | 一种乙磺酸尼达尼布的制备方法 |
| CN114761001A (zh) | 2019-12-04 | 2022-07-15 | 爱杜西亚药品有限公司 | 氮杂环丁烷lpa1受体拮抗剂与抗纤维化药剂的组合 |
| US20230135671A1 (en) | 2020-04-01 | 2023-05-04 | Boehringer Ingelheim International Gmbh | Use of biomarkers in the treatment of fibrotic conditions |
| EP4149475A1 (fr) | 2020-05-22 | 2023-03-22 | QX Therapeutics Inc. | Compositions et procédés permettant de traiter les lésions pulmonaires associées aux infections virales |
| CA3191013A1 (fr) * | 2020-08-07 | 2022-02-10 | Bdr Lifesciences Private Limited | Procede ameliore extremement efficace de preparation de nintedanib et d'un sel de qualite pharmaceutique de ce dernier |
| CN111848490B (zh) * | 2020-08-24 | 2021-09-24 | 江西国药有限责任公司 | 一种高纯度乙磺酸尼达尼布的制备方法 |
| CN113024439A (zh) * | 2021-03-28 | 2021-06-25 | 郑州大学 | 尼达尼布乙磺酸盐新晶型ⅰ的制备 |
| EP4098246A1 (fr) | 2021-05-31 | 2022-12-07 | Lotus Pharmaceutical Co., Ltd. | Formulation de nintedanib |
| WO2023161668A1 (fr) | 2022-02-28 | 2023-08-31 | Nuformix Technologies Limited | Compositions et méthodes de traitement de la fibrose pulmonaire idiopathique |
| WO2024037982A1 (fr) | 2022-08-16 | 2024-02-22 | Boehringer Ingelheim International Gmbh | Formulations pharmaceutiques de nintédanib pour utilisation intraoculaire |
| KR20240042322A (ko) | 2022-09-23 | 2024-04-02 | 삼아제약 주식회사 | 티로신 키나제 저해제를 유효성분으로 하는 약제학적 조성물 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB395546A (en) | 1931-10-12 | 1933-07-20 | Robert Pauli Scherer | Method of and apparatus for making capsules |
| US2720463A (en) | 1950-11-17 | 1955-10-11 | American Cyanamid Co | Gelatin capsule casting composition preparation |
| US2870062A (en) | 1956-04-27 | 1959-01-20 | Scherer Corp R P | Gelatin composition for capsules |
| DE3579384D1 (de) | 1984-07-24 | 1990-10-04 | Scherer Gmbh R P | Oxytetracyclin-hc1-weichgelatinekapseln und verfahren zu ihrer herstellung. |
| GB9718913D0 (en) * | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
| DE19816624A1 (de) * | 1998-04-15 | 1999-10-21 | Boehringer Ingelheim Pharma | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| KR100634039B1 (ko) * | 1999-08-23 | 2006-10-17 | 솔베이 파마슈티칼스 비. 브이 | 신규한 페닐피페라진 |
| US6762180B1 (en) * | 1999-10-13 | 2004-07-13 | Boehringer Ingelheim Pharma Kg | Substituted indolines which inhibit receptor tyrosine kinases |
| UA75054C2 (uk) * | 1999-10-13 | 2006-03-15 | Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг | Заміщені в положенні 6 індолінони, їх одержання та їх застосування як лікарського засобу |
| DE19949209A1 (de) * | 1999-10-13 | 2001-04-19 | Boehringer Ingelheim Pharma | In 5-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE10117204A1 (de) | 2001-04-06 | 2002-10-10 | Boehringer Ingelheim Pharma | In 6-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE10233500A1 (de) * | 2002-07-24 | 2004-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 3-Z-[1-(4-(N-((4-Methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylen]-6-methoxycarbonyl-2-indolinon-Monoethansulfonat und dessen Verwendung als Arzneimittel |
-
2002
- 2002-07-24 DE DE10233500A patent/DE10233500A1/de not_active Withdrawn
-
2003
- 2003-07-18 JP JP2004525239A patent/JP5039279B2/ja not_active Expired - Lifetime
- 2003-07-18 SI SI200332162T patent/SI1527047T1/sl unknown
- 2003-07-18 WO PCT/EP2003/007822 patent/WO2004013099A1/fr active Application Filing
- 2003-07-18 DK DK03766212.9T patent/DK1527047T3/da active
- 2003-07-18 ME MEP-2008-537A patent/ME00353B/fr unknown
- 2003-07-18 AT AT03766212T patent/ATE551322T1/de active
- 2003-07-18 EA EA200500146A patent/EA008684B1/ru active Protection Beyond IP Right Term
- 2003-07-18 MX MXPA04012785A patent/MXPA04012785A/es active IP Right Grant
- 2003-07-18 RS YU20050046A patent/RS52283B/sr unknown
- 2003-07-18 CN CNB038175304A patent/CN100351235C/zh not_active Ceased
- 2003-07-18 PT PT03766212T patent/PT1527047E/pt unknown
- 2003-07-18 BR BRPI0312811A patent/BRPI0312811B8/pt active IP Right Grant
- 2003-07-18 NZ NZ538367A patent/NZ538367A/en not_active IP Right Cessation
- 2003-07-18 EP EP11172210A patent/EP2386543A1/fr not_active Withdrawn
- 2003-07-18 ES ES03766212T patent/ES2384968T3/es not_active Expired - Lifetime
- 2003-07-18 UA UAA200501637A patent/UA78352C2/uk unknown
- 2003-07-18 EP EP03766212A patent/EP1527047B1/fr not_active Expired - Lifetime
- 2003-07-18 IL IL16640503A patent/IL166405A0/xx unknown
- 2003-07-18 PL PL372996A patent/PL223758B1/pl unknown
- 2003-07-18 KR KR1020057001207A patent/KR101145691B1/ko active IP Right Grant
- 2003-07-18 AU AU2003254376A patent/AU2003254376B2/en active Active
- 2003-07-18 CA CA2493310A patent/CA2493310C/fr not_active Expired - Lifetime
- 2003-07-21 US US10/623,971 patent/US7119093B2/en not_active Expired - Lifetime
- 2003-07-22 MY MYPI20032748A patent/MY136883A/en unknown
- 2003-07-22 EG EG2003070712A patent/EG24562A/xx active
- 2003-07-22 PE PE2003000728A patent/PE20040704A1/es active IP Right Grant
- 2003-07-23 AR AR20030102633A patent/AR040662A1/es not_active Ceased/Invalidation/Refusal/Rejection/Nullification
- 2003-07-23 TW TW092120101A patent/TWI285635B/zh active
- 2003-07-23 UY UY27904A patent/UY27904A1/es not_active Application Discontinuation
- 2003-12-16 SA SA03240446A patent/SA03240446B1/ar unknown
-
2004
- 2004-12-03 ZA ZA200409814A patent/ZA200409814B/xx unknown
-
2005
- 2005-01-20 IL IL166405A patent/IL166405A/en active IP Right Grant
- 2005-01-21 HR HRP20050070AA patent/HRP20050070B1/hr not_active IP Right Cessation
- 2005-01-24 EC EC2005005571A patent/ECSP055571A/es unknown
- 2005-02-23 NO NO20050985A patent/NO330486B1/no not_active IP Right Cessation
- 2005-11-24 HK HK05110630A patent/HK1078851A1/xx not_active IP Right Cessation
-
2006
- 2006-07-28 US US11/460,677 patent/US20060258681A1/en not_active Abandoned
-
2012
- 2012-06-13 CY CY20121100538T patent/CY1112916T1/el unknown
-
2013
- 2013-12-20 AR ARP130104954A patent/AR094217A2/es not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO330486B1 (no) | 3-z-(1-(4-(n-((4-4metyl-piperazin-1-yl)-metylkarbonyl)-n-metyl-amino)-anilino)-1-fenyl-metylen)-6-metoksykarb onyl-2-indolinon-monoetansulfonat, farmasoytisk preparat med og metbolitt av denne, fremstilling av farmasoytisk preparat og anvendelse av forbindelsen for fremstilling av farmasoytisk preparat for behandling av sykdom | |
| RU2663663C2 (ru) | Соль омекамтива мекарбила и способ ее получения | |
| EP2362873B1 (fr) | Nouvelle forme cristalline de malate de sunitinib | |
| JPH03271288A (ja) | インドール誘導体 | |
| WO2017016463A1 (fr) | Inhibiteur de l'egfr et sel pharmaceutiquement acceptable et polymorphe de celui-ci, et utilisation associée | |
| TW202302587A (zh) | 異喹啉酮類化合物及其用途 | |
| US20220315576A1 (en) | Polymorph of cdk9 inhibitor and preparation method for polymorph and use thereof | |
| CN107980038A (zh) | 沙库巴曲钙盐 | |
| KR20030042038A (ko) | 온단세트론 히드로클로라이드의 신규한 결정 형태 및용매화물 형태와 이들의 제조 방법 | |
| CN105461587A (zh) | Ahu-377半钙盐晶型及其制备方法和应用 | |
| JP2018518515A (ja) | フェニルアミノピリミジン化合物またはその塩の多形物 | |
| RU2518076C1 (ru) | Новое производное индазола или его соль и промежуточное соединение для их получения, а также антиоксидант с их использованием, и применение производных индазола или его соли | |
| JP2015500255A (ja) | ２−（２−メチルアミノ−ピリミジン−４−イル）−１ｈ−インドール−５−カルボン酸［（ｓ）−１−カルバモイル−２−（フェニル−ピリミジン−２−イル−アミノ）−エチル］−アミドの結晶形 | |
| EP2238108B1 (fr) | Formes de sel d'un dérivé de 6-fluoro-1,2-dihydro-2-oxo-3h-indol-3-ylidène, procédé de fabrication et compositions pharmaceutiques le contenant | |
| CN102666528A (zh) | 晶体cdc7 抑制剂盐 | |
| NO322240B1 (no) | Substituerte bisindolylmaleimider, deres fremstilling, farmasoytiske preparater inneholdende slike, samt anvendelse av slike forbindelser for fremstilling av medikamenter for inhibering av celleproliferasjon | |
| JP2024526242A (ja) | チアゾール－ラクタム－スピロ複素環化合物及びその適用 | |
| TW201211036A (en) | Useful salts of indazole derivative | |
| JPH068296B2 (ja) | アミノクロマノール誘導体 | |
| JPH0625231A (ja) | イソインダゾール誘導体 | |
| SK288226B6 (sk) | Kryštalická alfa-forma Imatinib mezylátu s novým habitom a spôsob jeho prípravy a použitie |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |