DK3019497T3 - Nyt salt af 3-[(3-{[4-(4-morpholinylmethyl)-1h-pyrrol-2-yl]methylen}-2-oxo-2,3-dihydro-1h-indol-5-yl)methyl]-1,3-thiazolidin-2,4-dion, fremstilling deraf og formuleringer indeholdende disse - Google Patents
Nyt salt af 3-[(3-{[4-(4-morpholinylmethyl)-1h-pyrrol-2-yl]methylen}-2-oxo-2,3-dihydro-1h-indol-5-yl)methyl]-1,3-thiazolidin-2,4-dion, fremstilling deraf og formuleringer indeholdende disse Download PDFInfo
- Publication number
- DK3019497T3 DK3019497T3 DK14758600.2T DK14758600T DK3019497T3 DK 3019497 T3 DK3019497 T3 DK 3019497T3 DK 14758600 T DK14758600 T DK 14758600T DK 3019497 T3 DK3019497 T3 DK 3019497T3
- Authority
- DK
- Denmark
- Prior art keywords
- methyl
- compound
- pyrrol
- oxo
- methylene
- Prior art date
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- 150000003839 salts Chemical class 0.000 title claims description 9
- AREYWCZYVPSHGS-UHFFFAOYSA-N 3-[[3-[[4-(morpholin-4-ylmethyl)-1h-pyrrol-2-yl]methylidene]-2-oxo-1h-indol-5-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1CC1=CC=C(NC(=O)C2=CC=3NC=C(CN4CCOCC4)C=3)C2=C1 AREYWCZYVPSHGS-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- HLEPAHCDDMLYAE-UHFFFAOYSA-N methanesulfonic acid 3-[[3-[[4-(morpholin-4-ylmethyl)-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indol-5-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CS(O)(=O)=O.O=C1CSC(=O)N1Cc1ccc2NC(=O)C(=Cc3cc(CN4CCOCC4)c[nH]3)c2c1 HLEPAHCDDMLYAE-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 239000013078 crystal Substances 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- -1 4-morpholinylmethyl Chemical group 0.000 claims description 4
- 229910002056 binary alloy Inorganic materials 0.000 claims description 4
- 238000010586 diagram Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 206010039491 Sarcoma Diseases 0.000 claims description 3
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
- 230000005540 biological transmission Effects 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 229940079156 Proteasome inhibitor Drugs 0.000 claims 1
- 230000000340 anti-metabolite Effects 0.000 claims 1
- 229940100197 antimetabolite Drugs 0.000 claims 1
- 239000002256 antimetabolite Substances 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 210000003238 esophagus Anatomy 0.000 claims 1
- 231100000024 genotoxic Toxicity 0.000 claims 1
- 230000001738 genotoxic effect Effects 0.000 claims 1
- 229940043355 kinase inhibitor Drugs 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 230000000394 mitotic effect Effects 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 1
- 239000002574 poison Substances 0.000 claims 1
- 231100000614 poison Toxicity 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- 239000003207 proteasome inhibitor Substances 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920003223 poly(pyromellitimide-1,4-diphenyl ether) Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
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- 239000000725 suspension Substances 0.000 description 1
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- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (14)
1. 3-[(3-{[4-(4-morpholinylmethyl)-1 /-/-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1/-/indol-5-yl) methyl] -1,3-thiazolidin-2,4-dion methansulfonat med formel (II):
hvor notationen
betyder, at dobbeltbindingen har Z eller E-konfiguration.
2. Forbindelsen ifølge krav 1, som er Z-isomeren af 3-[(3-{[4-(4-morpholinyl-methyl)-1 H-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1 /-/-indol-5-yl)methyl]-1,3-thiazolidin-2,4-dion-methansulfonat.
3. Forbindelse ifølge krav 1 eller 2, kendetegnet ved sit X-pulverrøntgendiffrak-tionsdiagram af Bragg-vinkler 2 theta (udtrykt i° ± 0,2) 12,86; 15,13; 15.50; 17,70; 18.25; 18.71; 20.11; 21,46; 21,67; 21.89; 22.29; 22,58; 24,57; 25,82; 26,33.
4. Forbindelse ifølge krav 1 eller 2, kendetegnet ved følgende parametre opnået fra pulverdiagrammet, der er udført på et Panalytical Xpert-Pro MPD diffraktome-ter (kobber-antikatode) i transmissionsmode med et vinkelområde på 3-55° 2Θ, et trin på 0,017° og 35,5 s pr trin, hvilket giver mulighed forfølgende krystalparametre at blive identificeret: - enhedscelleparametre: a = 15,0958 (5) A, b = 18,4586 (6) A, c = 8,8269 (2) Å, β = 94,074 (1)°,y = 90° - rumgruppe: C1 c1 (9) - volumen af enhedscellen: Venhedsceiie = 2453,37600 Å3.
5. Fremgangsmåden til at opnå forbindelsen med formlen (II) ifølge krav 1, kendetegnet ved, at der som udgangsmateriale anvendes 3-[(3-{[4-(4-morpholinyl-methyl)-1 H-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1 /-/indol-5-yl)methyl]-1,3-thiazolidin-2,4-dion, som anbringes i opløsning i et opløsningsmiddel/vand binært system, hvortil der tilsættes fra 1 til 2 molækvivalenter methansulfonsyre, som omrøres indtil udfældning af methansulfonatet, som filtreres fra.
6. Fremgangsmåden til at opnå forbindelsen med formlen (II) ifølge krav 1, kendetegnet ved, at der som udgangsmateriale anvendes 3-[(3-{[4-(4-morpholinyl-methyl)-1 H-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1 /-/-indol-5-yl)methyl]-1,3-thiazolidin-2,4-dion-hydrochlorid, som opløses i et opløsningsmiddel/vand binære system, hvis pH indstilles på 8 ved tilsætning af en base, det dannede salt fjernes ved filtrering, hvorefter filtratet opvarmes, og der tilsættes methansulfonsyre, blandingen omrøres og afkøles indtil udfældning af methansulfonatet, som filtreres fra.
7. Farmaceutisk sammensætning, der omfatter forbindelsen med formlen (II) ifølge et hvilket som helst af kravene 1 til 4 i kombination med et eller flere farmaceutisk acceptable excipienser.
8. Farmaceutisk sammensætning ifølge krav 7, kendetegnet ved, at forbindelsen med formlen (II) er Z-isomeren af 3-[(3-{[4-(4-morpholinylmethyl)-1/-/-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1 /-/-indol-5-yl)methyl]-1,3-thiazolidin-2,4-dion-methansulfonat.
9. Farmaceutisk sammensætning ifølge krav 7 eller 8 til anvendelse til fremstilling af medikamenter til anvendelse i behandlingen af cancere i tyktarm, bryst, lever, nyrer, hjerne og spiserøret, melanomer, myelomer, ovariecancere, ikke-småcel-let lungecancer, småcellet lungecancer, prostatacancer og pancreascancer, sarkomer.
10. Kombination af en forbindelse med formlen (II) ifølge et hvilket som helst af kravene 1 til 4 med et anticancermiddel, der er valgt blandt genotoksiske midler, mitotiske gifte, antimetabolitter, proteasominhibitorer og kinaseinhibitorer.
11. Kombinationen ifølge krav 10, kendetegnet ved, at forbindelsen med formlen (II) er Z-isomeren af 3-[(3-{[4-(4-morpholinylmethyl)-1/-/-pyrrol-2-yl]-methylene}-2-oxo-2,3-dihydro-1 /-/-indol-5-yl)methyl]-1,3-thiazolidin-2,4-dion-methansulfonat.
12. Anvendelse af en kombination ifølge krav 10 eller 11 til fremstilling af medikamenter til anvendelse til behandling af cancere.
13. Forbindelse med formel (II) ifølge et hvilket som helst af kravene 1 til 4 i kombination med strålebehandling til anvendelse ved behandling af cancere.
14. Forbindelse med formel (II) til brug ifølge krav 13, hvilken forbindelse er Z-isomeren af 3-[(3-{[4-(4-morpholinylmethyl)-1 /-/-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1H-indol-5-yl)methyl]-1,3-thiazolidin-2,4-dionmethansulfonat.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1356870A FR3008411B1 (fr) | 2013-07-12 | 2013-07-12 | Nouveau sel de la 3-[(3-{[4-(4-morpholinylmethyl)-1h-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1h-indol-5-yl)methyl]-1,3-thiazolidine-2,4-dione, sa preparation, et les formulations qui le contiennent |
| PCT/FR2014/051783 WO2015004395A1 (fr) | 2013-07-12 | 2014-07-11 | Nouveau sel de la 3-[(3-{[4-(4-morpholinylméthyl)-1h-pyrrol-2-yl]méthylène}-2-oxo-2,3-dihydro-1h-indol-5-yl)méthyl]-1,3-thiazolidine-2,4-dione, sa préparation, et les formulations qui le contiennent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK3019497T3 true DK3019497T3 (da) | 2017-08-07 |
Family
ID=50424327
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK14758600.2T DK3019497T3 (da) | 2013-07-12 | 2014-07-11 | Nyt salt af 3-[(3-{[4-(4-morpholinylmethyl)-1h-pyrrol-2-yl]methylen}-2-oxo-2,3-dihydro-1h-indol-5-yl)methyl]-1,3-thiazolidin-2,4-dion, fremstilling deraf og formuleringer indeholdende disse |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10245270B2 (en) * | 2013-07-12 | 2019-04-02 | Les Laboratoires Servier | Salt of 3-[(3-{[4-(4-morpholinylmethyl)-1H-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1H-indol-5-yl)methyl]-1,3-thiazolidine-2,4-dione, its preparation, and formulations containing it |
| FR3039401B1 (fr) * | 2015-07-31 | 2018-07-13 | Les Laboratoires Servier | Nouvelle association entre le 3-[(3-{[4-(4-morpholinylmethyl)-1h-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1h-indol-5-yl)methyl]-1,3-thiazolidine-2,4-dione et un inhibiteur de la tyr kinase du egfr |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1329390C (zh) * | 2000-02-15 | 2007-08-01 | 苏根公司 | 吡咯取代的2－二氢吲哚酮蛋白激酶抑制剂 |
| CA2424689A1 (en) * | 2000-10-17 | 2002-04-25 | Merck & Co., Inc. | Orally active salts with tyrosine kinase activity |
| AR042586A1 (es) * | 2001-02-15 | 2005-06-29 | Sugen Inc | 3-(4-amidopirrol-2-ilmetiliden)-2-indolinona como inhibidores de la protein quinasa; sus composiciones farmaceuticas; un metodo para la modulacion de la actividad catalitica de la proteinquinasa; un metodo para tratar o prevenir una afeccion relacionada con la proteinquinasa |
| WO2003057690A1 (en) * | 2001-12-27 | 2003-07-17 | Theravance, Inc. | Indolinone derivatives useful as protein kinase inhibitors |
| EP1680401A2 (en) * | 2003-10-24 | 2006-07-19 | Schering Aktiengesellschaft | Indolinone derivatives and their use in treating disease-states such as cancer |
| PL1959948T3 (pl) | 2005-12-05 | 2012-12-31 | Xenoport Inc | Metanosulfonian proleku lewodopy, jego kompozycje, oraz jego zastosowania |
| FR2948940B1 (fr) * | 2009-08-04 | 2011-07-22 | Servier Lab | Nouveaux derives dihydroindolones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
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2013
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