DE60211124T2 - Abbau von Epothilonen - Google Patents
Abbau von Epothilonen Download PDFInfo
- Publication number
- DE60211124T2 DE60211124T2 DE60211124T DE60211124T DE60211124T2 DE 60211124 T2 DE60211124 T2 DE 60211124T2 DE 60211124 T DE60211124 T DE 60211124T DE 60211124 T DE60211124 T DE 60211124T DE 60211124 T2 DE60211124 T2 DE 60211124T2
- Authority
- DE
- Germany
- Prior art keywords
- formula
- compound
- epothilone
- scheme
- degradation
- 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.)
- Expired - Lifetime
Links
- 230000015556 catabolic process Effects 0.000 title claims description 3
- 238000006731 degradation reaction Methods 0.000 title claims description 3
- 229930013356 epothilone Natural products 0.000 title abstract description 5
- 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 description 3
- 238000000034 method Methods 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract 14
- BEFZAMRWPCMWFJ-JRBBLYSQSA-N Epothilone C Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C=C\C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C BEFZAMRWPCMWFJ-JRBBLYSQSA-N 0.000 claims description 7
- BEFZAMRWPCMWFJ-UHFFFAOYSA-N desoxyepothilone A Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC=CCC1C(C)=CC1=CSC(C)=N1 BEFZAMRWPCMWFJ-UHFFFAOYSA-N 0.000 claims description 7
- BEFZAMRWPCMWFJ-QJKGZULSSA-N epothilone C Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 BEFZAMRWPCMWFJ-QJKGZULSSA-N 0.000 claims description 7
- XOZIUKBZLSUILX-SDMHVBBESA-N Epothilone D Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C(/C)=C/C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C XOZIUKBZLSUILX-SDMHVBBESA-N 0.000 claims description 6
- XOZIUKBZLSUILX-UHFFFAOYSA-N desoxyepothilone B Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC(C)=CCC1C(C)=CC1=CSC(C)=N1 XOZIUKBZLSUILX-UHFFFAOYSA-N 0.000 claims description 6
- XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 claims description 6
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
- 239000005977 Ethylene Substances 0.000 claims description 3
- 238000005865 alkene metathesis reaction Methods 0.000 claims description 2
- 238000010931 ester hydrolysis Methods 0.000 claims description 2
- 238000000855 fermentation Methods 0.000 claims description 2
- 230000004151 fermentation Effects 0.000 claims description 2
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 abstract description 2
- 150000003883 epothilone derivatives Chemical class 0.000 abstract 2
- 239000011984 grubbs catalyst Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- -1 hexane / tert-butyl methyl ester Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 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
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/14—Nitrogen or oxygen as hetero atom and at least one other diverse hetero ring atom in the same ring
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
- C12P17/181—Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/62—Carboxylic acid esters
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/141111—Diverse hetero atoms in same or different rings [e.g., alkaloids, opiates, etc.]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Silicon Polymers (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
- Abbau von Epothilonen
- Epothilone vom Typ C und Typ D gehören zum Stand der Technik und sind besonders durch eine C=C Doppelbindung an den Positionen 12 und 13 und einem Wasserstoffatom an der Position 12 (Typ C) oder einer Alkylgruppe (Typ D) gekennzeichnet.
- Gemäß einer Ausführungsform betrifft die Erfindung ein Verfahren zum Abbau von einem Epothilon C oder einem Epothilon D, bei dem man das Epothilon C oder das Epothilon D einer Olefin-Metathese in Gegenwart von Ethylen und danach einer fakultativen Esterhydrolyse unterwirft (Schema 1).
- Erfindungsgemäß kann das Epothilon C oder D ein Fermentationsprodukt sein.
- Experimenteller Teil
- 12,13-Seco-Epothilon C (2a):
- 450 mg Epothilon C (1) (0,95 mmol) wurden in 250 ml Dichlormethan gelöst, mit Ethylen gesättigt und nach Zugabe von 60 mg Grubb's Katalysator (PhCHRuCl2]P(Cy)3]2) 24 Stunden lang gerührt. Nach Zugabe von weiteren 60 mg Katalysator und 24-stündigem Rühren wurde die dunkle Lösung zur Trockne eingedampft und der Rückstand durch Chromatographie über Kieselgel mit dem Lösungsmittelsystem Hexan/tert.-Butylmethylester/Methanol 80:20:1 gereinigt. Die erste Fraktion enthielt 360 mg (75%) an 2a, die zweite 100 mg (22%) an wiedergewonnenem Ausgangsmaterial 1.
2a: 1H-NMR (CDCl3), 300 MHz): δ = 6.95 (s, 19-H), 6.02 (s, 17-H), 5.89-5.64 (m, 12-H, 13-H), 5.16-4.89 (m, 12a-H2, 13a-H2), 5.37 (t, J = 7 Hz, 15-H), 4.24 (ddd, J = 10, 3, 3.5 Hz, 3-H), 3.36 (s, OH), 3.34 (d, J = 8 Hz, 7-H), 3.25 (dq, J = 1.5, 7 Hz, 8-H), 3.21 (d, J = 3.8 Hz, OH), 2.70 (s, 21-H3), 2.52-2.32 (m, 2-H2, 14-H2), 2.07 (d, J = 1.5 Hz, 16-Me), 2.05-1.95 (m, 11-H2), 1.8-1.1 (m, 6-H, 8-H, 9-H2, 10-H2), 1.18 (s, 4-Me), 1.10 (s, 4-Me), 1.04 (d, J = 7 Hz, 6-Me), 0.83 (d, J = 7 Hz, 8-Me).
ESI-MS (positive Ionen) m/z = 506 [M + H+], CI-MS (NH3 positive Ionen) m/z = 506 [M + H+] (22%), 380 (100%).
Claims (3)
- Verfahren zum Abbau von einem Epothilon C oder einem Epothilon D, bei dem man das Epothilon C oder das Epothilon D einer Olefin-Metathesis in Gegenwart von Ethylen und danach einer fakultativen Esterhydrolyse unterwirft (Schema I).
- Verfahren nach Anspruch 1, bei dem Epothilon C oder Epothilon D ein Fermentationsprodukt sind.
- Verbindung der Formel 2a, erhältlich nach einem Verfahren gemäß einem oder mehreren der vorhergehenden Ansprüche.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01104448 | 2001-02-27 | ||
| EP01104448 | 2001-02-27 | ||
| PCT/EP2002/002105 WO2002072858A2 (en) | 2001-02-27 | 2002-02-27 | Degradation of epothilones and ethynyl substituted epothilones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60211124D1 DE60211124D1 (de) | 2006-06-08 |
| DE60211124T2 true DE60211124T2 (de) | 2006-11-30 |
Family
ID=8176579
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60211124T Expired - Lifetime DE60211124T2 (de) | 2001-02-27 | 2002-02-27 | Abbau von Epothilonen |
| DE60213884T Expired - Lifetime DE60213884T2 (de) | 2001-02-27 | 2002-02-27 | Verfahren zur Herstellung von Epothilonen |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60213884T Expired - Lifetime DE60213884T2 (de) | 2001-02-27 | 2002-02-27 | Verfahren zur Herstellung von Epothilonen |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7157595B2 (de) |
| EP (2) | EP1564217B1 (de) |
| JP (1) | JP2004522801A (de) |
| KR (1) | KR20030084952A (de) |
| CN (1) | CN1501980A (de) |
| AT (2) | ATE325201T1 (de) |
| BR (1) | BR0207675A (de) |
| CA (1) | CA2437707A1 (de) |
| CZ (1) | CZ20032291A3 (de) |
| DE (2) | DE60211124T2 (de) |
| HU (1) | HUP0303895A3 (de) |
| IL (1) | IL157312A0 (de) |
| MX (1) | MXPA03007466A (de) |
| NO (1) | NO20033784D0 (de) |
| NZ (2) | NZ539204A (de) |
| PL (1) | PL362556A1 (de) |
| RU (1) | RU2003128953A (de) |
| WO (1) | WO2002072858A2 (de) |
| ZA (1) | ZA200306034B (de) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2273083C (en) * | 1996-12-03 | 2012-09-18 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| DE19826988A1 (de) * | 1998-06-18 | 1999-12-23 | Biotechnolog Forschung Gmbh | Epothilon-Nebenkomponenten |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US7649006B2 (en) * | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| ATE350383T1 (de) * | 2002-08-23 | 2007-01-15 | Sloan Kettering Inst Cancer | Synthese von epothilonen, zwischenprodukte dafür, analoga und deren verwendungen |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0057736B1 (de) * | 1981-02-05 | 1986-11-20 | Phillips Petroleum Company | Olefin-Disproportionierungs-Verfahren und Katalysator |
| PT1186606E (pt) | 1995-11-17 | 2004-08-31 | Biotechnolog Forschung Mbh Gbf | Derivados do epotilone sua preparacao e utilizacao |
| NZ334821A (en) * | 1996-08-30 | 2000-12-22 | Novartis Ag | Method for producing epothilones |
| US5969145A (en) | 1996-08-30 | 1999-10-19 | Novartis Ag | Process for the production of epothilones and intermediate products within the process |
| DK1367057T3 (da) | 1996-11-18 | 2009-01-19 | Biotechnolog Forschung Gmbh | Epothiloner E og F |
| US6441186B1 (en) * | 1996-12-13 | 2002-08-27 | The Scripps Research Institute | Epothilone analogs |
| US6380394B1 (en) | 1996-12-13 | 2002-04-30 | The Scripps Research Institute | Epothilone analogs |
| CN1544436A (zh) * | 1997-02-25 | 2004-11-10 | ���＼���о�����˾��GBF�� | 3，7-保护的环氧噻嗪酮-n-氧化物及其制备方法 |
| US6605599B1 (en) | 1997-07-08 | 2003-08-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
| 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 |
| US6498257B1 (en) | 1998-04-21 | 2002-12-24 | Bristol-Myers Squibb Company | 2,3-olefinic epothilone derivatives |
| US6211412B1 (en) * | 1999-03-29 | 2001-04-03 | The University Of Kansas | Synthesis of epothilones |
| US6518421B1 (en) | 2000-03-20 | 2003-02-11 | Bristol-Myers Squibb Company | Process for the preparation of epothilone analogs |
| US6593115B2 (en) | 2000-03-24 | 2003-07-15 | Bristol-Myers Squibb Co. | Preparation of epothilone intermediates |
-
2002
- 2002-02-27 CA CA002437707A patent/CA2437707A1/en not_active Abandoned
- 2002-02-27 DE DE60211124T patent/DE60211124T2/de not_active Expired - Lifetime
- 2002-02-27 CZ CZ20032291A patent/CZ20032291A3/cs unknown
- 2002-02-27 DE DE60213884T patent/DE60213884T2/de not_active Expired - Lifetime
- 2002-02-27 EP EP04019590A patent/EP1564217B1/de not_active Expired - Lifetime
- 2002-02-27 JP JP2002571909A patent/JP2004522801A/ja not_active Withdrawn
- 2002-02-27 NZ NZ539204A patent/NZ539204A/en unknown
- 2002-02-27 CN CNA028055349A patent/CN1501980A/zh active Pending
- 2002-02-27 HU HU0303895A patent/HUP0303895A3/hu unknown
- 2002-02-27 IL IL15731202A patent/IL157312A0/xx unknown
- 2002-02-27 AT AT02719946T patent/ATE325201T1/de not_active IP Right Cessation
- 2002-02-27 RU RU2003128953/04A patent/RU2003128953A/ru not_active Application Discontinuation
- 2002-02-27 NZ NZ527557A patent/NZ527557A/en unknown
- 2002-02-27 BR BR0207675-6A patent/BR0207675A/pt not_active IP Right Cessation
- 2002-02-27 US US10/468,919 patent/US7157595B2/en not_active Expired - Lifetime
- 2002-02-27 EP EP02719946A patent/EP1364040B1/de not_active Expired - Lifetime
- 2002-02-27 AT AT04019590T patent/ATE335746T1/de not_active IP Right Cessation
- 2002-02-27 WO PCT/EP2002/002105 patent/WO2002072858A2/en active IP Right Grant
- 2002-02-27 MX MXPA03007466A patent/MXPA03007466A/es unknown
- 2002-02-27 KR KR10-2003-7011281A patent/KR20030084952A/ko not_active Application Discontinuation
- 2002-02-27 PL PL02362556A patent/PL362556A1/xx not_active Application Discontinuation
-
2003
- 2003-08-05 ZA ZA200306034A patent/ZA200306034B/en unknown
- 2003-08-26 NO NO20033784A patent/NO20033784D0/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA03007466A (es) | 2003-12-08 |
| EP1564217A2 (de) | 2005-08-17 |
| WO2002072858A2 (en) | 2002-09-19 |
| EP1564217A3 (de) | 2005-08-31 |
| DE60213884D1 (de) | 2006-09-21 |
| DE60213884T2 (de) | 2007-02-22 |
| JP2004522801A (ja) | 2004-07-29 |
| CN1501980A (zh) | 2004-06-02 |
| NO20033784L (no) | 2003-08-26 |
| ATE325201T1 (de) | 2006-06-15 |
| IL157312A0 (en) | 2004-02-19 |
| NO20033784D0 (no) | 2003-08-26 |
| BR0207675A (pt) | 2004-03-09 |
| NZ527557A (en) | 2005-05-27 |
| EP1564217B1 (de) | 2006-08-09 |
| ATE335746T1 (de) | 2006-09-15 |
| HUP0303895A3 (en) | 2007-06-28 |
| US7157595B2 (en) | 2007-01-02 |
| HUP0303895A2 (hu) | 2004-03-29 |
| RU2003128953A (ru) | 2005-03-10 |
| PL362556A1 (en) | 2004-11-02 |
| US20040092560A1 (en) | 2004-05-13 |
| EP1364040A2 (de) | 2003-11-26 |
| DE60211124D1 (de) | 2006-06-08 |
| CZ20032291A3 (cs) | 2004-02-18 |
| ZA200306034B (en) | 2004-08-05 |
| KR20030084952A (ko) | 2003-11-01 |
| CA2437707A1 (en) | 2002-09-19 |
| NZ539204A (en) | 2005-12-23 |
| EP1364040B1 (de) | 2006-05-03 |
| WO2002072858A3 (en) | 2002-12-19 |
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