CN102993213A - 有机化合物 - Google Patents
有机化合物 Download PDFInfo
- Publication number
- CN102993213A CN102993213A CN2012104320940A CN201210432094A CN102993213A CN 102993213 A CN102993213 A CN 102993213A CN 2012104320940 A CN2012104320940 A CN 2012104320940A CN 201210432094 A CN201210432094 A CN 201210432094A CN 102993213 A CN102993213 A CN 102993213A
- Authority
- CN
- China
- Prior art keywords
- staurosporine
- benzoyl
- crystal form
- preparation
- ethanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000002894 organic compounds Chemical class 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 122
- 239000013078 crystal Substances 0.000 claims description 95
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 claims description 25
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 claims description 25
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 claims description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 8
- 229960004217 benzyl alcohol Drugs 0.000 claims description 8
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- BMGQWWVMWDBQGC-IIFHNQTCSA-N midostaurin Chemical compound CN([C@H]1[C@H]([C@]2(C)O[C@@H](N3C4=CC=CC=C4C4=C5C(=O)NCC5=C5C6=CC=CC=C6N2C5=C43)C1)OC)C(=O)C1=CC=CC=C1 BMGQWWVMWDBQGC-IIFHNQTCSA-N 0.000 abstract description 133
- 238000002360 preparation method Methods 0.000 abstract description 48
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- 238000002560 therapeutic procedure Methods 0.000 abstract 1
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- 229960004756 ethanol Drugs 0.000 description 37
- 238000003483 aging Methods 0.000 description 33
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- 238000000926 separation method Methods 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 11
- 229950010895 midostaurin Drugs 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 239000003814 drug Substances 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 239000007921 spray Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000000634 powder X-ray diffraction Methods 0.000 description 8
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- 239000000126 substance Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 102000003923 Protein Kinase C Human genes 0.000 description 5
- 108090000315 Protein Kinase C Proteins 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 230000001476 alcoholic effect Effects 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229960000935 dehydrated alcohol Drugs 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
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- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 2
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- -1 [1,7] benzo diazonin-11-yl Chemical group 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000005352 clarification Methods 0.000 description 2
- 201000010989 colorectal carcinoma Diseases 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 238000002329 infrared spectrum Methods 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
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000036457 multidrug resistance Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
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- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
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- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
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- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
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- 239000007903 gelatin capsule Substances 0.000 description 1
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- 238000005469 granulation Methods 0.000 description 1
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- 238000002513 implantation Methods 0.000 description 1
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- 230000036512 infertility Effects 0.000 description 1
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- 230000003993 interaction Effects 0.000 description 1
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- 239000008101 lactose Substances 0.000 description 1
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- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
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- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
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- 210000003205 muscle Anatomy 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
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- 235000009566 rice Nutrition 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Extraction Or Liquid Replacement (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62534304P | 2004-11-05 | 2004-11-05 | |
| US60/625,343 | 2004-11-05 | ||
| US64213105P | 2005-01-07 | 2005-01-07 | |
| US60/642,131 | 2005-01-07 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200580037222 Division CN101048416A (zh) | 2004-11-05 | 2005-11-03 | 有机化合物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102993213A true CN102993213A (zh) | 2013-03-27 |
Family
ID=35501294
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012104320940A Pending CN102993213A (zh) | 2004-11-05 | 2005-11-03 | 有机化合物 |
| CN2012101018747A Pending CN102627658A (zh) | 2004-11-05 | 2005-11-03 | 有机化合物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101018747A Pending CN102627658A (zh) | 2004-11-05 | 2005-11-03 | 有机化合物 |
Country Status (31)
| Country | Link |
|---|---|
| US (2) | US8198435B2 (enExample) |
| EP (3) | EP1812448B1 (enExample) |
| JP (4) | JP5057986B2 (enExample) |
| KR (3) | KR101333851B1 (enExample) |
| CN (2) | CN102993213A (enExample) |
| AR (1) | AR052322A1 (enExample) |
| AU (2) | AU2005300693B2 (enExample) |
| BR (1) | BRPI0517689A (enExample) |
| CA (1) | CA2584911C (enExample) |
| CY (1) | CY1113059T1 (enExample) |
| DK (1) | DK1812448T3 (enExample) |
| EC (1) | ECSP12007431A (enExample) |
| ES (1) | ES2388142T3 (enExample) |
| GT (1) | GT200500311A (enExample) |
| HK (1) | HK1211587A1 (enExample) |
| HR (1) | HRP20120652T1 (enExample) |
| IL (3) | IL182691A (enExample) |
| JO (1) | JO2897B1 (enExample) |
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| TN (1) | TNSN07165A1 (enExample) |
| TW (4) | TWI530500B (enExample) |
| WO (1) | WO2006048296A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111393454A (zh) * | 2020-05-07 | 2020-07-10 | 奥锐特药业(天津)有限公司 | 米哚妥林的新晶型及其制备方法 |
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| KR101462693B1 (ko) * | 2006-08-16 | 2014-11-17 | 노파르티스 아게 | 고도 결정질 치료용 화합물의 고체 분산체 제조 방법 |
| EP2327706A1 (en) * | 2009-11-30 | 2011-06-01 | Novartis AG | Polymorphous forms III and IV of N-benzoyl-staurosporine |
| KR20160008267A (ko) | 2014-07-14 | 2016-01-22 | 주식회사 윈스 | 네트워크 기반 영상감시체계에서의 사용자 행위 분석 시스템 |
| EP3592749A1 (en) * | 2017-03-06 | 2020-01-15 | Teva Pharmaceutical Works Ltd. | Solid state forms of midostaurin |
| WO2019215759A1 (en) * | 2018-05-09 | 2019-11-14 | Alaparthi Lakshmi Prasad | An improved process for preparation of midostaurin |
| IT201900004729A1 (it) | 2019-03-29 | 2020-09-29 | Procos Spa | Processo per la preparazione di midostaurina ad elevato grado di purezza |
| US20220242880A1 (en) * | 2019-06-24 | 2022-08-04 | Dr. Reddy?s Laboratories Limited | Process for preparation of midostaurin |
| IT201900014346A1 (it) * | 2019-08-08 | 2021-02-08 | Procos Spa | Processo per la preparazione di midostaurina amorfa con un basso contenuto di solvente organico residuo |
| IT202000004291A1 (it) | 2020-03-02 | 2021-09-02 | Indena Spa | Processo per la purificazione di alcaloidi indolo carbazolici |
| CN115124551B (zh) * | 2021-03-24 | 2024-04-30 | 奥锐特药业(天津)有限公司 | 一种高纯度米哚妥林的制备方法 |
| WO2023205504A1 (en) * | 2022-04-22 | 2023-10-26 | Rutgers, The State University Of New Jersey | Formulations and methods for treating epidermolysis bullosa simplex and related conditions |
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| JPS5373501A (en) * | 1976-12-11 | 1978-06-30 | Kitasato Inst | Novel antibiotics amm2282 and process for preparing same |
| JPS60185719A (ja) | 1984-03-06 | 1985-09-21 | Ajinomoto Co Inc | 抗腫瘍剤 |
| US5093330A (en) * | 1987-06-15 | 1992-03-03 | Ciba-Geigy Corporation | Staurosporine derivatives substituted at methylamino nitrogen |
| IL86632A0 (en) * | 1987-06-15 | 1988-11-30 | Ciba Geigy Ag | Derivatives substituted at methyl-amino nitrogen |
| US5073633A (en) * | 1989-03-23 | 1991-12-17 | Bristol-Myers Company | BMY-41950 antitumor antibiotic |
| US5096330A (en) * | 1990-06-21 | 1992-03-17 | M-B-W Inc. | Pitch control mechanism for a surface finishing machine |
| JPH05247055A (ja) * | 1992-03-03 | 1993-09-24 | Meiji Seika Kaisha Ltd | スタウロスポリン誘導体及びそれを含有する抗腫瘍効果増強剤 |
| JPH05247955A (ja) | 1992-03-06 | 1993-09-24 | Taisei Corp | 擁壁の施工方法 |
| US5344926A (en) | 1992-06-22 | 1994-09-06 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing staurosporine derivatives |
| WO1995032975A1 (en) * | 1994-06-01 | 1995-12-07 | Ciba-Geigy Ag | Indolocarbazole derivatives for sensitizing multidrug-resistant cells to antitumor agents |
| RU2191175C2 (ru) * | 1995-12-11 | 2002-10-20 | Сефалон, Инкорпорейтед | Конденсированные изоиндолоны в качестве ингибиторов протеинкиназы с |
| BR9917475B1 (pt) * | 1999-08-30 | 2013-07-23 | processo para a manufatura de compostos, e, modificação do processo. | |
| CA2439097C (en) | 2001-03-26 | 2010-10-12 | Novartis Ag | Pharmaceutical compositions |
| KR100407758B1 (ko) * | 2001-08-27 | 2003-12-01 | 씨제이 주식회사 | 스타틴의 제조에 있어서 락톤화 방법 |
| WO2004094645A1 (en) * | 2003-04-22 | 2004-11-04 | Lonza Ag | Process for the recovery of staurosporine from a fermentation broth |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111393454A (zh) * | 2020-05-07 | 2020-07-10 | 奥锐特药业(天津)有限公司 | 米哚妥林的新晶型及其制备方法 |
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