ZA200007059B - Epothilone derivatives and their synthesis and use. - Google Patents
Epothilone derivatives and their synthesis and use. Download PDFInfo
- Publication number
- ZA200007059B ZA200007059B ZA200007059A ZA200007059A ZA200007059B ZA 200007059 B ZA200007059 B ZA 200007059B ZA 200007059 A ZA200007059 A ZA 200007059A ZA 200007059 A ZA200007059 A ZA 200007059A ZA 200007059 B ZA200007059 B ZA 200007059B
- Authority
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- South Africa
- Prior art keywords
- formula
- absent
- butyl
- methyl
- compound
- Prior art date
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- 238000003786 synthesis reaction Methods 0.000 title claims description 11
- 230000015572 biosynthetic process Effects 0.000 title claims description 10
- 150000003883 epothilone derivatives Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 61
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 239000001301 oxygen Substances 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 15
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 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 claims description 8
- -1 n- propyl Chemical group 0.000 claims description 8
- 229930013356 epothilone Natural products 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 230000002062 proliferating effect Effects 0.000 claims description 6
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 5
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- 125000001153 fluoro group Chemical group F* 0.000 claims 2
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- 210000004027 cell Anatomy 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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- 230000000694 effects Effects 0.000 description 2
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- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
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- 230000032050 esterification Effects 0.000 description 1
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- 238000006266 etherification reaction Methods 0.000 description 1
- FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
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- 235000011087 fumaric acid Nutrition 0.000 description 1
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- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 208000025440 neoplasm of neck Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 108020004707 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940026778 other chemotherapeutics in atc Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
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- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
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- 238000006116 polymerization reaction Methods 0.000 description 1
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- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid group Chemical class S(N)(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
-
- 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
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- 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
- 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
-
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Silicon Polymers (AREA)
- Plural Heterocyclic Compounds (AREA)
- Lubricants (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/102,602 US6380394B1 (en) | 1996-12-13 | 1998-06-22 | Epothilone analogs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200007059B true ZA200007059B (en) | 2002-01-30 |
Family
ID=22290705
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200007059A ZA200007059B (en) | 1998-06-22 | 2000-11-30 | Epothilone derivatives and their synthesis and use. |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US6380394B1 (cs) |
| EP (2) | EP1089998B1 (cs) |
| JP (1) | JP4681732B2 (cs) |
| KR (3) | KR20090066332A (cs) |
| CN (1) | CN1192031C (cs) |
| AT (1) | ATE343573T1 (cs) |
| AU (1) | AU757854B2 (cs) |
| BR (1) | BR9911420A (cs) |
| CA (1) | CA2334342C (cs) |
| CY (1) | CY1105863T1 (cs) |
| CZ (1) | CZ301783B6 (cs) |
| DE (1) | DE69933767T2 (cs) |
| DK (1) | DK1089998T3 (cs) |
| ES (1) | ES2273502T3 (cs) |
| HU (1) | HUP0102711A3 (cs) |
| ID (1) | ID28210A (cs) |
| IL (3) | IL139784A0 (cs) |
| MX (1) | MXPA00012443A (cs) |
| NO (1) | NO328417B1 (cs) |
| NZ (1) | NZ508622A (cs) |
| PL (1) | PL197648B1 (cs) |
| PT (1) | PT1089998E (cs) |
| RU (1) | RU2227142C2 (cs) |
| SK (2) | SK287864B6 (cs) |
| TR (1) | TR200003844T2 (cs) |
| WO (1) | WO1999067252A2 (cs) |
| ZA (1) | ZA200007059B (cs) |
Families Citing this family (94)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0873341B1 (de) | 1995-11-17 | 2003-09-10 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Epothilonderivate, herstellung und verwendung |
| DE59711647D1 (de) | 1996-11-18 | 2004-06-24 | Biotechnolog Forschung Gmbh | Epothilon d, dessen herstellung und dessen verwendung als cytostatisches mittel bzw. als pflanzenschutzmittel |
| US20050043376A1 (en) * | 1996-12-03 | 2005-02-24 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| AU756699B2 (en) | 1996-12-03 | 2003-01-23 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6204388B1 (en) * | 1996-12-03 | 2001-03-20 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US6867305B2 (en) * | 1996-12-03 | 2005-03-15 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US6660758B1 (en) * | 1996-12-13 | 2003-12-09 | The Scripps Research Institute | Epothilone analogs |
| 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 |
| FR2775187B1 (fr) * | 1998-02-25 | 2003-02-21 | Novartis Ag | Utilisation de l'epothilone b pour la fabrication d'une preparation pharmaceutique antiproliferative et d'une composition comprenant l'epothilone b comme agent antiproliferatif in vivo |
| US6498257B1 (en) | 1998-04-21 | 2002-12-24 | Bristol-Myers Squibb Company | 2,3-olefinic epothilone derivatives |
| US6399638B1 (en) | 1998-04-21 | 2002-06-04 | Bristol-Myers Squibb Company | 12,13-modified epothilone derivatives |
| DE19820599A1 (de) * | 1998-05-08 | 1999-11-11 | Biotechnolog Forschung Gmbh | Epothilonderivate, Verfahren zu deren Herstellung und deren Verwendung |
| DE19826988A1 (de) * | 1998-06-18 | 1999-12-23 | Biotechnolog Forschung Gmbh | Epothilon-Nebenkomponenten |
| US6410301B1 (en) | 1998-11-20 | 2002-06-25 | Kosan Biosciences, Inc. | Myxococcus host cells for the production of epothilones |
| AU768220B2 (en) | 1998-11-20 | 2003-12-04 | Kosan Biosciences, Inc. | Recombinant methods and materials for producing epothilone and epothilone derivatives |
| DK1157023T3 (da) * | 1999-02-22 | 2004-03-29 | Bristol Myers Squibb Co | C-21-modificerede epothiloner |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| PL215901B1 (pl) | 1999-04-15 | 2014-02-28 | Bristol Myers Squibb Co | Cykliczny inhibitor bialkowych kinaz tyrozynowych, jego zastosowanie oraz kompozycja farmaceutyczna zawierajaca taki zwiazek |
| US7125875B2 (en) | 1999-04-15 | 2006-10-24 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| WO2001038317A2 (en) * | 1999-11-24 | 2001-05-31 | GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) | Fungicidal melithiazole derivatives |
| US6518421B1 (en) * | 2000-03-20 | 2003-02-11 | Bristol-Myers Squibb Company | Process for the preparation of epothilone analogs |
| AU2001266583A1 (en) * | 2000-05-26 | 2001-12-11 | Kosan Biosciences, Inc. | Epothilone derivatives and methods for making and using the same |
| HUP0302905A3 (en) * | 2000-09-22 | 2006-05-29 | Biotechnolog Forschung Gmbh | Triazolo-epothilone-analogs, process for their preparation and pharmaceutical compositions containing them |
| WO2002030356A2 (en) * | 2000-10-13 | 2002-04-18 | The University Of Mississipi | Synthesis of epothilones and relates analogs |
| CZ20032021A3 (cs) | 2001-01-25 | 2004-05-12 | Bristol@Myersásquibbácompany | Způsoby podávání analogů epothilonu při léčbě rakoviny |
| WO2002058699A1 (en) * | 2001-01-25 | 2002-08-01 | Bristol-Myers Squibb Company | Pharmaceutical forms of epothilones for oral administration |
| SK8552003A3 (en) | 2001-01-25 | 2004-06-08 | Bristol Myers Squibb Co | Parenteral formulation containing epothilone analogs |
| JP2004522774A (ja) | 2001-02-20 | 2004-07-29 | ブリストル−マイヤーズ スクイブ カンパニー | エポチロン誘導体を用いる耐性腫瘍の治療 |
| CN1610549A (zh) | 2001-02-20 | 2005-04-27 | 布里斯托尔-迈尔斯斯奎布公司 | 用于治疗难治肿瘤的埃坡霉素衍生物 |
| DE60213884T2 (de) * | 2001-02-27 | 2007-02-22 | GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) | Verfahren zur Herstellung von Epothilonen |
| ES2384789T3 (es) | 2001-03-14 | 2012-07-12 | Bristol-Myers Squibb Company | Combinación de un análogo de epotilona y agentes quimioterapéuticos para el tratamiento de enfermedades proliferativas |
| JP2004532888A (ja) * | 2001-06-01 | 2004-10-28 | ブリストル−マイヤーズ スクイブ カンパニー | エポチロン誘導体 |
| EP1420780B1 (en) * | 2001-08-23 | 2008-10-01 | Novartis AG | Cyclopropyl and cyclobutyl epothilone analogs |
| WO2003026744A1 (en) * | 2001-09-25 | 2003-04-03 | Alcon, Inc. | The use of epothilones and analogs in conjunction with ophthalmic surgery |
| MXPA04003878A (es) * | 2001-10-25 | 2004-07-08 | Novartis Ag | Combinaciones que comprenden un inhibidor selectivo de cicloxigenasa-2. |
| EP1456664A1 (en) * | 2001-12-07 | 2004-09-15 | Novartis AG | Use of alpha-tubulin acetylation levels as a biomarker for protein deacetylase inhibitors |
| CA2471509A1 (en) | 2002-01-14 | 2003-07-17 | Novartis Ag | Combinations comprising epothilones and anti-metabolites |
| TW200303202A (en) * | 2002-02-15 | 2003-09-01 | Bristol Myers Squibb Co | Method of preparation of 21-amino epothilone derivatives |
| ATE452896T1 (de) | 2002-03-12 | 2010-01-15 | Bristol Myers Squibb Co | C3-cyanoepothilonderivate |
| WO2003077903A1 (en) | 2002-03-12 | 2003-09-25 | Bristol-Myers Squibb Company | C12-cyano epothilone derivatives |
| TW200403994A (en) * | 2002-04-04 | 2004-03-16 | Bristol Myers Squibb Co | Oral administration of EPOTHILONES |
| TW200400191A (en) * | 2002-05-15 | 2004-01-01 | Bristol Myers Squibb Co | Pharmaceutical compositions and methods of using C-21 modified epothilone derivatives |
| US7405234B2 (en) | 2002-05-17 | 2008-07-29 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| AU2003243561A1 (en) | 2002-06-14 | 2003-12-31 | Bristol-Myers Squibb Company | Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases |
| JP4276171B2 (ja) * | 2002-08-02 | 2009-06-10 | ノバルティス アクチエンゲゼルシャフト | エポシロン誘導体 |
| US7384964B2 (en) * | 2002-08-23 | 2008-06-10 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| PT1767535E (pt) * | 2002-08-23 | 2010-02-24 | Sloan Kettering Inst Cancer | Síntese de epotilonas, respectivos intermediários, análogos e suas utilizações |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| GB0221312D0 (en) * | 2002-09-13 | 2002-10-23 | Novartis Ag | Organic compounds |
| EP2287168B1 (en) | 2002-09-23 | 2013-02-13 | Bristol-Myers Squibb Company | Methods for the preparation, isolation and purification of epothilone B, and X-ray crystal structures of epothilone B |
| ES2279139T3 (es) * | 2002-10-15 | 2007-08-16 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Uso de los derivados de epotilona para el tratamiento del hiperparatiroidismo. |
| EP1567487A4 (en) | 2002-11-15 | 2005-11-16 | Bristol Myers Squibb Co | OPEN-CHAINED, PROLYL-FROSTED MODULATORS OF ANDROGEN RECEPTOR FUNCTION |
| US20050171167A1 (en) * | 2003-11-04 | 2005-08-04 | Haby Thomas A. | Process and formulation containing epothilones and analogs thereof |
| EP1559447A1 (en) | 2004-01-30 | 2005-08-03 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Use of epothilones in the treatment of neuronal connectivity defects such as schizophrenia and autism |
| US7820702B2 (en) | 2004-02-04 | 2010-10-26 | Bristol-Myers Squibb Company | Sulfonylpyrrolidine modulators of androgen receptor function and method |
| US7378426B2 (en) | 2004-03-01 | 2008-05-27 | Bristol-Myers Squibb Company | Fused heterotricyclic compounds as inhibitors of 17β-hydroxysteroid dehydrogenase 3 |
| US7625923B2 (en) | 2004-03-04 | 2009-12-01 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| US7696241B2 (en) | 2004-03-04 | 2010-04-13 | Bristol-Myers Squibb Company | Bicyclic compounds as modulators of androgen receptor function and method |
| GB0405898D0 (en) * | 2004-03-16 | 2004-04-21 | Novartis Ag | Organic compounds |
| US10675326B2 (en) | 2004-10-07 | 2020-06-09 | The Board Of Trustees Of The University Of Illinois | Compositions comprising cupredoxins for treating cancer |
| EP1674098A1 (en) | 2004-12-23 | 2006-06-28 | Schering Aktiengesellschaft | Stable and tolerable parental formulations of highly reactive organic drug substances with low or no solubility in water |
| AU2006336468B2 (en) | 2005-02-11 | 2012-04-12 | University Of Southern California | Method of expressing proteins with disulfide bridges |
| US7772177B2 (en) | 2005-05-18 | 2010-08-10 | Aegera Therapeutics, Inc. | BIR domain binding compounds |
| WO2007015929A2 (en) * | 2005-07-27 | 2007-02-08 | University Of Toledo | Epothilone analogues |
| CA2628227A1 (en) * | 2005-11-22 | 2007-05-31 | The Scripps Research Institute | Chemical synthesis of a highly potent epothilone |
| US7653731B2 (en) * | 2006-02-24 | 2010-01-26 | Microsoft Corporation | Management of connections to external data |
| US8008256B2 (en) * | 2006-05-01 | 2011-08-30 | University Of Southern California | Combination therapy for treatment of cancer |
| SG10201407457UA (en) | 2006-05-16 | 2014-12-30 | Pharmascience Inc | Iap bir domain binding compounds |
| JP2010511408A (ja) | 2006-12-04 | 2010-04-15 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・イリノイ | 癌をＣｐＧリッチＤＮＡおよびキュプレドキシンで治療するための組成物および方法 |
| JP2010518123A (ja) | 2007-02-08 | 2010-05-27 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・イリノイ | 癌をキュプレドキシンで予防するための組成物および方法 |
| WO2008118327A1 (en) * | 2007-03-23 | 2008-10-02 | University Of Toledo | Conformationally restrained epothilone analogues as anti-leukemic agents |
| EP2065054A1 (en) | 2007-11-29 | 2009-06-03 | Bayer Schering Pharma Aktiengesellschaft | Combinations comprising a prostaglandin and uses thereof |
| DE102007059752A1 (de) | 2007-12-10 | 2009-06-18 | Bayer Schering Pharma Aktiengesellschaft | Funktionalisierte, feste Polymernanopartikel enthaltend Epothilone |
| EP2070521A1 (en) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Surface-modified nanoparticles |
| WO2010000817A1 (en) * | 2008-07-03 | 2010-01-07 | Pharma Mar, S.A. | Antitumoral macrolides |
| WO2010056901A2 (en) | 2008-11-13 | 2010-05-20 | University Of Southern California | Method of expressing proteins with disulfide bridges with enhanced yields and activity |
| EP2210584A1 (en) | 2009-01-27 | 2010-07-28 | Bayer Schering Pharma Aktiengesellschaft | Stable polymeric composition comprising an epothilone and an amphiphilic block copolymer |
| AU2011214057B2 (en) | 2010-02-12 | 2016-11-17 | Pharmascience Inc. | IAP BIR domain binding compounds |
| AU2011255647A1 (en) | 2010-05-18 | 2012-11-15 | Cerulean Pharma Inc. | Compositions and methods for treatment of autoimmune and other diseases |
| BR112013018534B1 (pt) | 2011-01-20 | 2021-04-06 | Board Of Regents, The University Of Texas System | Agente de contraste, seus métodos de preparação, e produto de combinação |
| CN102863474A (zh) | 2011-07-09 | 2013-01-09 | 陈小平 | 一类治疗细胞增殖性疾病的铂化合物、其制备方法和应用 |
| CN102993239A (zh) | 2011-09-19 | 2013-03-27 | 陈小平 | 离去基团含氨基或烷胺基的丁二酸衍生物的铂类化合物 |
| US9717803B2 (en) | 2011-12-23 | 2017-08-01 | Innate Pharma | Enzymatic conjugation of polypeptides |
| WO2014009426A2 (en) | 2012-07-13 | 2014-01-16 | Innate Pharma | Screening of conjugated antibodies |
| US10036010B2 (en) | 2012-11-09 | 2018-07-31 | Innate Pharma | Recognition tags for TGase-mediated conjugation |
| EP2924044B1 (en) | 2012-11-17 | 2018-10-31 | Beijing Shuobai Pharmaceutical Co., LTD | Platinum compound of malonic acid derivative having leaving group containing amino or alkylamino |
| CA2898996A1 (en) * | 2013-01-23 | 2014-07-31 | The University Of Toledo | Highly selective anti-cancer agents targeting non-small cell lung cancer and other forms of cancer |
| EP2968582B1 (en) | 2013-03-15 | 2020-07-01 | Innate Pharma | Solid phase tgase-mediated conjugation of antibodies |
| EP3010547B1 (en) | 2013-06-20 | 2021-04-21 | Innate Pharma | Enzymatic conjugation of polypeptides |
| AU2014283185B2 (en) | 2013-06-21 | 2019-05-02 | Araris Biotech Ltd. | Enzymatic conjugation of polypeptides |
| EP3371176A4 (en) * | 2015-10-16 | 2019-09-04 | William Marsh Rice University | EPOTHILON ANALOGUE, SYNTHESIS METHOD, TREATMENT METHOD AND MEDICAMENT CONJUGATE THEREFOR |
| WO2019092148A1 (en) | 2017-11-10 | 2019-05-16 | Innate Pharma | Antibodies with functionalized glutamine residues |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW221441B (cs) * | 1991-01-25 | 1994-03-01 | Taiho Pharmaceutical Co Ltd | |
| DE4138042C2 (de) | 1991-11-19 | 1993-10-14 | Biotechnolog Forschung Gmbh | Epothilone, deren Herstellungsverfahren sowie diese Verbindungen enthaltende Mittel |
| EP0873341B1 (de) | 1995-11-17 | 2003-09-10 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Epothilonderivate, herstellung und verwendung |
| EP0923583A1 (de) | 1996-08-30 | 1999-06-23 | Novartis AG | Verfahren zur herstellung von epothilonen und zwischenprodukte innerhalb des verfahrens |
| DE59711647D1 (de) | 1996-11-18 | 2004-06-24 | Biotechnolog Forschung Gmbh | Epothilon d, dessen herstellung und dessen verwendung als cytostatisches mittel bzw. als pflanzenschutzmittel |
| AU756699B2 (en) | 1996-12-03 | 2003-01-23 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6660758B1 (en) * | 1996-12-13 | 2003-12-09 | The Scripps Research Institute | Epothilone analogs |
| US6441186B1 (en) | 1996-12-13 | 2002-08-27 | The Scripps Research Institute | Epothilone analogs |
| AU736062B2 (en) | 1997-02-25 | 2001-07-26 | Gesellschaft Fur Biotechnologische Forschung Mbh | Epothilones which are modified in the side chain |
| US6605599B1 (en) | 1997-07-08 | 2003-08-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
| US7407975B2 (en) | 1997-08-09 | 2008-08-05 | Bayer Schering Pharma Ag | Epothilone derivatives, method for producing same and their pharmaceutical use |
| DE19744135C1 (de) | 1997-09-29 | 1999-03-25 | Schering Ag | Beschichtete medizinische Implantate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Restenoseprophylaxe |
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