ZA200304296B - Process for the isolation and purification of epothilones. - Google Patents
Process for the isolation and purification of epothilones. Download PDFInfo
- Publication number
- ZA200304296B ZA200304296B ZA200304296A ZA200304296A ZA200304296B ZA 200304296 B ZA200304296 B ZA 200304296B ZA 200304296 A ZA200304296 A ZA 200304296A ZA 200304296 A ZA200304296 A ZA 200304296A ZA 200304296 B ZA200304296 B ZA 200304296B
- Authority
- ZA
- South Africa
- Prior art keywords
- epothilones
- epothilone
- mixture
- solvent
- resin
- Prior art date
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- 229930013356 epothilone Natural products 0.000 title claims description 97
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 title claims description 92
- 238000000034 method Methods 0.000 title claims description 53
- 238000000746 purification Methods 0.000 title claims description 8
- 238000002955 isolation Methods 0.000 title claims description 6
- 239000002904 solvent Substances 0.000 claims description 53
- HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 claims description 50
- 229920005989 resin Polymers 0.000 claims description 46
- 239000011347 resin Substances 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- 238000003795 desorption Methods 0.000 claims description 37
- QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 claims description 35
- QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 claims description 33
- 150000003883 epothilone derivatives Chemical class 0.000 claims description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 26
- 150000002825 nitriles Chemical class 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 20
- 238000001704 evaporation Methods 0.000 claims description 18
- 230000008020 evaporation Effects 0.000 claims description 17
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 16
- 150000002430 hydrocarbons Chemical class 0.000 claims description 14
- 229920003002 synthetic resin Polymers 0.000 claims description 13
- 239000000057 synthetic resin Substances 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 12
- 238000000926 separation method Methods 0.000 claims description 12
- 238000004587 chromatography analysis Methods 0.000 claims description 11
- 239000004215 Carbon black (E152) Substances 0.000 claims description 10
- 229930195733 hydrocarbon Natural products 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 238000010828 elution Methods 0.000 claims description 8
- 239000000284 extract Substances 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 238000004366 reverse phase liquid chromatography Methods 0.000 claims description 6
- 238000005377 adsorption chromatography Methods 0.000 claims description 5
- 239000003849 aromatic solvent Substances 0.000 claims description 5
- 230000008025 crystallization Effects 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000011877 solvent mixture Substances 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
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- 125000003118 aryl group Chemical group 0.000 claims description 2
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- XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 claims 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- 239000012071 phase Substances 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 229960004592 isopropanol Drugs 0.000 description 15
- 238000000605 extraction Methods 0.000 description 11
- 238000001179 sorption measurement Methods 0.000 description 10
- 238000005191 phase separation Methods 0.000 description 9
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- 238000001914 filtration Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 7
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000001246 bromo group Chemical group Br* 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 125000002346 iodo group Chemical group I* 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- GWHJZXXIDMPWGX-UHFFFAOYSA-N 1,2,4-trimethylbenzene Chemical compound CC1=CC=C(C)C(C)=C1 GWHJZXXIDMPWGX-UHFFFAOYSA-N 0.000 description 4
- CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 4
- IVSZLXZYQVIEFR-UHFFFAOYSA-N 1,3-Dimethylbenzene Natural products CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- 229920006026 co-polymeric resin Polymers 0.000 description 4
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 229940073584 methylene chloride Drugs 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
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- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 150000004996 alkyl benzenes Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
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- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
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- NUMXHEUHHRTBQT-AATRIKPKSA-N 2,4-dimethoxy-1-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C(OC)=C1 NUMXHEUHHRTBQT-AATRIKPKSA-N 0.000 description 1
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- OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
- 208000035126 Facies Diseases 0.000 description 1
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- 230000009897 systematic effect Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- RCINICONZNJXQF-XAZOAEDWSA-N taxol® Chemical compound O([C@@H]1[C@@]2(CC(C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3(C21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-XAZOAEDWSA-N 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- 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)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Silicon Polymers (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0029895.0A GB0029895D0 (en) | 2000-12-07 | 2000-12-07 | Organic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200304296B true ZA200304296B (en) | 2004-04-23 |
Family
ID=9904660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200304296A ZA200304296B (en) | 2000-12-07 | 2003-06-02 | Process for the isolation and purification of epothilones. |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US6946561B2 (es) |
| EP (1) | EP1345944B1 (es) |
| JP (1) | JP4287650B2 (es) |
| KR (1) | KR100894990B1 (es) |
| CN (1) | CN1263761C (es) |
| AR (1) | AR031902A1 (es) |
| AT (1) | ATE292132T1 (es) |
| AU (2) | AU2493602A (es) |
| BR (1) | BR0115991A (es) |
| CA (1) | CA2433414C (es) |
| CZ (1) | CZ301664B6 (es) |
| DE (1) | DE60109814T2 (es) |
| DK (1) | DK1345944T3 (es) |
| EC (1) | ECSP034641A (es) |
| ES (1) | ES2239687T3 (es) |
| GB (1) | GB0029895D0 (es) |
| HK (1) | HK1059618A1 (es) |
| HU (1) | HU224910B1 (es) |
| IL (2) | IL156088A0 (es) |
| MX (1) | MXPA03005097A (es) |
| MY (1) | MY128409A (es) |
| NO (1) | NO329164B1 (es) |
| NZ (1) | NZ526197A (es) |
| PE (1) | PE20020568A1 (es) |
| PL (1) | PL209406B1 (es) |
| PT (1) | PT1345944E (es) |
| RU (1) | RU2285007C2 (es) |
| SI (1) | SI1345944T1 (es) |
| SK (1) | SK287356B6 (es) |
| TW (1) | TWI286137B (es) |
| WO (1) | WO2002046196A1 (es) |
| ZA (1) | ZA200304296B (es) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6867305B2 (en) | 1996-12-03 | 2005-03-15 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| JP4579351B2 (ja) * | 1996-12-03 | 2010-11-10 | スローン−ケッタリング インスティトュート フォア キャンサー リサーチ | エポチロンの合成とその中間体及びその類似物並びにその使用 |
| US6194181B1 (en) * | 1998-02-19 | 2001-02-27 | Novartis Ag | Fermentative preparation process for and crystal forms of cytostatics |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| GB0029895D0 (en) * | 2000-12-07 | 2001-01-24 | Novartis Ag | Organic compounds |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| DK1767535T3 (da) * | 2002-08-23 | 2010-04-12 | Sloan Kettering Inst Cancer | Syntese af epothiloner, mellemprodukter deraf, analoge og deres anvendelse |
| MXPA05003006A (es) * | 2002-09-23 | 2005-06-22 | Squibb Bristol Myers Co | Metodos para la preparacion, aislamiento y purificacion de epotilona b y estructuras cristalinas de rayos x y de epotilona b. |
| FR2846520B1 (fr) | 2002-11-06 | 2006-09-29 | Roquette Freres | Utilisation de maltodextrines branchees comme liants de granulation |
| KR100681811B1 (ko) * | 2005-03-15 | 2007-02-12 | 성균관대학교산학협력단 | 생물학적 대사부산물의 효율적인 제거를 통한 유용 이차대사산물의 제조방법 |
| NZ574194A (en) | 2006-08-16 | 2011-12-22 | Novartis Ag | Crystal form of epothilone b and use in pharmaceutical compositions |
| US8906947B2 (en) | 2008-02-01 | 2014-12-09 | Zhejiang Hisun Pharmaceutical Co., Ltd. | Method for the separation and purification of epothilones |
| CN105797168A (zh) | 2010-05-18 | 2016-07-27 | 天蓝制药公司 | 用于治疗自身免疫性疾病或其它疾病的组合物和方法 |
| KR101372563B1 (ko) * | 2011-12-26 | 2014-03-14 | 주식회사 삼양바이오팜 | 에포틸론 함유물질로부터 에포틸론 ａ와 ｂ의 추출 및 정제 방법 |
| CN110964029B (zh) * | 2019-12-19 | 2020-11-03 | 鲁南制药集团股份有限公司 | 一种埃博霉素b发酵液的预处理方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4138042C2 (de) * | 1991-11-19 | 1993-10-14 | Biotechnolog Forschung Gmbh | Epothilone, deren Herstellungsverfahren sowie diese Verbindungen enthaltende Mittel |
| EP1367057B1 (de) * | 1996-11-18 | 2008-09-17 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Epothilone E und F |
| ATE224882T1 (de) * | 1997-07-16 | 2002-10-15 | Schering Ag | Thiazolderivate, verfahren zur herstellung und verwendung |
| US6365749B1 (en) * | 1997-12-04 | 2002-04-02 | Bristol-Myers Squibb Company | Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs |
| US6194181B1 (en) * | 1998-02-19 | 2001-02-27 | Novartis Ag | Fermentative preparation process for and crystal forms of cytostatics |
| DE19826988A1 (de) * | 1998-06-18 | 1999-12-23 | Biotechnolog Forschung Gmbh | Epothilon-Nebenkomponenten |
| EP1652926B1 (en) * | 2000-04-28 | 2009-09-30 | Kosan Biosciences, Inc. | Crystalline epothilone d |
| GB0029895D0 (en) * | 2000-12-07 | 2001-01-24 | Novartis Ag | Organic compounds |
-
2000
- 2000-12-07 GB GBGB0029895.0A patent/GB0029895D0/en not_active Ceased
-
2001
- 2001-11-28 PE PE2001001192A patent/PE20020568A1/es not_active Application Discontinuation
- 2001-12-03 TW TW090129838A patent/TWI286137B/zh not_active IP Right Cessation
- 2001-12-05 AT AT01994791T patent/ATE292132T1/de active
- 2001-12-05 AR ARP010105667A patent/AR031902A1/es active IP Right Grant
- 2001-12-05 BR BR0115991-7A patent/BR0115991A/pt not_active IP Right Cessation
- 2001-12-05 DE DE60109814T patent/DE60109814T2/de not_active Expired - Lifetime
- 2001-12-05 CZ CZ20031565A patent/CZ301664B6/cs not_active IP Right Cessation
- 2001-12-05 DK DK01994791T patent/DK1345944T3/da active
- 2001-12-05 CN CNB018201415A patent/CN1263761C/zh not_active Expired - Fee Related
- 2001-12-05 AU AU2493602A patent/AU2493602A/xx active Pending
- 2001-12-05 PL PL361884A patent/PL209406B1/pl not_active IP Right Cessation
- 2001-12-05 KR KR1020037007114A patent/KR100894990B1/ko not_active IP Right Cessation
- 2001-12-05 SK SK689-2003A patent/SK287356B6/sk not_active IP Right Cessation
- 2001-12-05 CA CA2433414A patent/CA2433414C/en not_active Expired - Fee Related
- 2001-12-05 ES ES01994791T patent/ES2239687T3/es not_active Expired - Lifetime
- 2001-12-05 MX MXPA03005097A patent/MXPA03005097A/es active IP Right Grant
- 2001-12-05 RU RU2003119659/04A patent/RU2285007C2/ru not_active IP Right Cessation
- 2001-12-05 US US10/433,808 patent/US6946561B2/en not_active Expired - Fee Related
- 2001-12-05 AU AU2002224936A patent/AU2002224936B2/en not_active Ceased
- 2001-12-05 EP EP01994791A patent/EP1345944B1/en not_active Expired - Lifetime
- 2001-12-05 WO PCT/EP2001/014771 patent/WO2002046196A1/en active Application Filing
- 2001-12-05 MY MYPI20015563A patent/MY128409A/en unknown
- 2001-12-05 JP JP2002547933A patent/JP4287650B2/ja not_active Expired - Fee Related
- 2001-12-05 PT PT01994791T patent/PT1345944E/pt unknown
- 2001-12-05 NZ NZ526197A patent/NZ526197A/en not_active IP Right Cessation
- 2001-12-05 SI SI200130358T patent/SI1345944T1/sl unknown
- 2001-12-05 IL IL15608801A patent/IL156088A0/xx active IP Right Grant
- 2001-12-05 HU HU0302579A patent/HU224910B1/hu not_active IP Right Cessation
-
2003
- 2003-05-22 IL IL156088A patent/IL156088A/en not_active IP Right Cessation
- 2003-06-02 ZA ZA200304296A patent/ZA200304296B/en unknown
- 2003-06-03 EC EC2003004641A patent/ECSP034641A/es unknown
- 2003-06-06 NO NO20032591A patent/NO329164B1/no not_active IP Right Cessation
-
2004
- 2004-02-11 HK HK04100923A patent/HK1059618A1/xx not_active IP Right Cessation
-
2005
- 2005-08-17 US US11/205,892 patent/US7569698B2/en not_active Expired - Fee Related
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