NO337476B1 - Derivater av ecteinascidinene, farmasøytiske preparater derav, og deres anvendelse ved fremstillingen av et medikament for behandling av kreft. - Google Patents
Derivater av ecteinascidinene, farmasøytiske preparater derav, og deres anvendelse ved fremstillingen av et medikament for behandling av kreft. Download PDFInfo
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- NO337476B1 NO337476B1 NO20040961A NO20040961A NO337476B1 NO 337476 B1 NO337476 B1 NO 337476B1 NO 20040961 A NO20040961 A NO 20040961A NO 20040961 A NO20040961 A NO 20040961A NO 337476 B1 NO337476 B1 NO 337476B1
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- Prior art keywords
- alkyl
- compound according
- carbon atoms
- groups
- compounds
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- 239000003814 drug Substances 0.000 title claims description 27
- 206010028980 Neoplasm Diseases 0.000 title claims description 10
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- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 7
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 title description 12
- 238000004519 manufacturing process Methods 0.000 title description 3
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- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 229940079593 drug Drugs 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 26
- -1 cyano, hydroxyl Chemical group 0.000 claims description 25
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- 239000001257 hydrogen Substances 0.000 claims description 19
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
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- 125000006413 ring segment Chemical group 0.000 claims description 13
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- 238000002360 preparation method Methods 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 6
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
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- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 2
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- 238000006243 chemical reaction Methods 0.000 description 24
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 20
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
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- 229960000977 trabectedin Drugs 0.000 description 15
- 125000003342 alkenyl group Chemical group 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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- 230000000259 anti-tumor effect Effects 0.000 description 9
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- 238000000338 in vitro Methods 0.000 description 8
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
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- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
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- 238000012216 screening Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 3
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- 210000004185 liver Anatomy 0.000 description 3
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
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- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000721 toxic potential Toxicity 0.000 description 1
- 231100000048 toxicity data Toxicity 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 239000003744 tubulin modulator Substances 0.000 description 1
- 210000001944 turbinate Anatomy 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
- Peptides Or Proteins (AREA)
- Compounds Of Unknown Constitution (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0119243.4A GB0119243D0 (en) | 2001-08-07 | 2001-08-07 | Antitumoral analogs of ET-743 |
| PCT/GB2002/003592 WO2003014127A1 (en) | 2001-08-07 | 2002-08-06 | Antitumoral analogs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20040961L NO20040961L (no) | 2004-03-05 |
| NO337476B1 true NO337476B1 (no) | 2016-04-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20040961A NO337476B1 (no) | 2001-08-07 | 2004-03-05 | Derivater av ecteinascidinene, farmasøytiske preparater derav, og deres anvendelse ved fremstillingen av et medikament for behandling av kreft. |
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| US (1) | US7763615B2 (https=) |
| EP (3) | EP1414828B9 (https=) |
| JP (2) | JP4684552B2 (https=) |
| KR (1) | KR20040032150A (https=) |
| CN (1) | CN100334094C (https=) |
| AT (1) | ATE374777T1 (https=) |
| AU (1) | AU2002313540B2 (https=) |
| CA (1) | CA2455768C (https=) |
| CY (1) | CY1107830T1 (https=) |
| DE (1) | DE60222775T2 (https=) |
| DK (1) | DK1414828T3 (https=) |
| ES (1) | ES2294151T3 (https=) |
| GB (1) | GB0119243D0 (https=) |
| HU (1) | HU229779B1 (https=) |
| IL (2) | IL160051A0 (https=) |
| MX (1) | MXPA04001240A (https=) |
| NO (1) | NO337476B1 (https=) |
| NZ (1) | NZ530837A (https=) |
| PL (1) | PL218295B1 (https=) |
| PT (1) | PT1414828E (https=) |
| RU (1) | RU2283842C2 (https=) |
| WO (1) | WO2003014127A1 (https=) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0202544D0 (en) * | 2002-02-04 | 2002-03-20 | Pharma Mar Sa | The synthesis of naturally occuring ecteinascidins and related compounds |
| US8716308B2 (en) | 2008-01-11 | 2014-05-06 | Albany Molecular Research, Inc. | (1-azinone)-substituted pyridoindoles |
| US8629158B2 (en) * | 2009-07-01 | 2014-01-14 | Albany Molecular Research, Inc. | Azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine MCH-1 antagonists, methods of making, and use thereof |
| US8637501B2 (en) * | 2009-07-01 | 2014-01-28 | Albany Molecular Research, Inc. | Azinone-substituted azepino[b]indole and pyrido-pyrrolo-azepine MCH-1 antagonists, methods of making, and use thereof |
| WO2011003012A1 (en) * | 2009-07-01 | 2011-01-06 | Albany Molecular Research, Inc. | Azinone-substituted azapolycycle mch-1 antagonists, methods of making, and use thereof |
| US9073925B2 (en) * | 2009-07-01 | 2015-07-07 | Albany Molecular Research, Inc. | Azinone-substituted azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine MCH-1 antagonists, methods of making, and use thereof |
| CN107033164A (zh) * | 2010-05-25 | 2017-08-11 | 法马马有限公司 | 制备海鞘素化合物的合成方法 |
| ME02395B (me) * | 2010-11-12 | 2016-09-20 | Pharma Mar Sa | Kombinovana terapija sa antitumorskim alkaloidima |
| RU2562432C2 (ru) | 2010-11-26 | 2015-09-10 | Нек Корпорейшн | Устройство видеокодирования, устройство видеодекодирования, способ видеокодирования, способ видеодекодирования и программа |
| US8993765B2 (en) | 2010-12-21 | 2015-03-31 | Albany Molecular Research, Inc. | Tetrahydro-azacarboline MCH-1 antagonists, methods of making, and uses thereof |
| WO2012088038A2 (en) | 2010-12-21 | 2012-06-28 | Albany Molecular Research, Inc. | Piperazinone-substituted tetrahydro-carboline mch-1 antagonists, methods of making, and uses thereof |
| CN108271369A (zh) | 2015-10-23 | 2018-07-10 | 法尔玛赞公司 | 用于制备色胺及其衍生物的新工艺 |
| HRP20231233T1 (hr) | 2017-04-27 | 2024-01-19 | Pharma Mar, S.A. | Antitumorski spojevi |
| TWI824043B (zh) * | 2018-10-25 | 2023-12-01 | 西班牙商瑪製藥股份有限公司 | 藥物抗體共軛物 |
| TW202116783A (zh) | 2019-09-03 | 2021-05-01 | 西班牙商瑪製藥股份有限公司 | 盧比克替定治療惡性間皮瘤 |
| CN112574234B (zh) * | 2019-09-27 | 2022-05-24 | 江苏恒瑞医药股份有限公司 | 一种海鞘素衍生物的制备方法 |
| MA56827B2 (fr) * | 2019-11-21 | 2023-09-27 | Pharma Mar Sa | Procédés de traitement du cancer du poumon à petites cellules avec des formulations de lurbinectédine |
| JP2023503318A (ja) * | 2019-11-21 | 2023-01-27 | ファルマ、マール、ソシエダード、アノニマ | ルルビネクテジン製剤で小細胞肺がんを処置する方法 |
| WO2021228414A1 (en) | 2020-05-14 | 2021-11-18 | Pharma Mar, S.A. | Methods of treating small cell lung cancer with lurbinectedin formulations |
| KR20230004714A (ko) | 2020-04-21 | 2023-01-06 | 파르마 마르, 에스.에이. | 약물 항체 접합체 |
| TW202144369A (zh) * | 2020-04-26 | 2021-12-01 | 大陸商江蘇恆瑞醫藥股份有限公司 | 海鞘素類衍生物及其製備方法與醫藥用途 |
| WO2022048775A1 (en) | 2020-09-04 | 2022-03-10 | Pharma Mar, S.A. | Combination of lurbinectedin and immune checkpoint inhibitor |
| WO2022101255A1 (en) | 2020-11-10 | 2022-05-19 | Pharma Mar, S.A. | Lurbinectedin and irinotecan combinations |
| IN202141039393A (https=) * | 2021-08-31 | 2023-03-03 | ||
| US20240415834A1 (en) | 2021-11-08 | 2024-12-19 | Pharma Mar, S.A. | Lurbinectedin and atezolizumab combinations |
| CN115246846B (zh) * | 2021-11-19 | 2024-10-01 | 江苏慧聚药业股份有限公司 | 卢比替定新晶型及其制备 |
| CN115304619A (zh) * | 2022-04-08 | 2022-11-08 | 上海皓元医药股份有限公司 | 一种卢比替定的晶型及其制备方法 |
| CN114940682A (zh) * | 2022-05-18 | 2022-08-26 | 博瑞制药(苏州)有限公司 | 芦比替定的晶型及其制备方法和用途 |
| WO2024186263A1 (en) * | 2023-03-07 | 2024-09-12 | Axcynsis Therapeutics Pte. Ltd. | Antibody-drug conjugates comprising trabectedin and lurbinectedin derivatives |
| WO2024188978A1 (en) | 2023-03-10 | 2024-09-19 | Pharma Mar, S.A. | Lurbinectedin as mcl-1 inhibitor and combinations thereof for use in treating cancer |
| WO2025059336A1 (en) * | 2023-09-13 | 2025-03-20 | Navinta, Llc | An improved process for preparation of lurbinectedin |
| WO2025077996A1 (en) | 2023-10-09 | 2025-04-17 | Pharma Mar, S.A. | Synthetic process for the manufacture of ecteinascidin compounds |
| EP4563149A1 (en) | 2023-11-30 | 2025-06-04 | Pharma Mar, S.A. | Lurbinectedin, ecubectedin and a related compound for use in the treatment of skin cancers |
| WO2025168075A1 (zh) * | 2024-02-08 | 2025-08-14 | 映恩生物科技(上海)有限公司 | 海鞘素类化合物及其应用 |
| WO2026022359A2 (en) | 2024-07-26 | 2026-01-29 | Pharma Mar, S.A. | Synthetic process for the manufacture of ecteinascidin compounds |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992009607A1 (en) * | 1990-11-30 | 1992-06-11 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins 736 and 722 |
| WO2000018233A1 (en) * | 1998-09-30 | 2000-04-06 | President And Fellows Of Harvard College | Synthetic analogs of ecteinascidin-743 |
| WO2000069862A2 (en) * | 1999-05-14 | 2000-11-23 | Pharma Mar, S.A. | Hemisynthetic method and intermediates thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59225189A (ja) | 1983-06-03 | 1984-12-18 | Shionogi & Co Ltd | キノナミン誘導体およびその製造法 |
| JPS6084288A (ja) | 1983-10-13 | 1985-05-13 | Shionogi & Co Ltd | シアノキノナミンアセテ−ト類およびその製造法 |
| US5089273A (en) * | 1986-06-09 | 1992-02-18 | Board Of Trustees Of The University Of Illinois | Ecteinascidins 729, 743, 745, 759A, 759B and 770 |
| JP2562162B2 (ja) | 1986-06-09 | 1996-12-11 | ユニバーシティ・オブ・イリノイ | エクテインアシジン７２９、７４３、７４５、７５９ａ、７５９ｂおよび７７０ |
| US5256663A (en) * | 1986-06-09 | 1993-10-26 | The Board Of Trustees Of The University Of Illinois | Compositions comprising ecteinascidins and a method of treating herpes simplex virus infections therewith |
| US5478932A (en) | 1993-12-02 | 1995-12-26 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins |
| US5721362A (en) | 1996-09-18 | 1998-02-24 | President And Fellows Of Harvard College | Process for producing ecteinascidin compounds |
| US5985876A (en) * | 1997-04-15 | 1999-11-16 | Univ Illinois | Nucleophile substituted ecteinascidins and N-oxide ecteinascidins |
| CN1157189C (zh) | 1998-04-06 | 2004-07-14 | 伊利诺伊大学评议会 | 半合成海鞘素 |
| EP1077698B1 (en) | 1998-05-11 | 2005-03-02 | Pharma Mar, S.A. | Metabolites of ecteinascidin 743 |
| JP2003520801A (ja) * | 2000-01-19 | 2003-07-08 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク | サフラマイシン−エクテイナシジン系列の化合物、それらの使用及び合成 |
| JP5219323B2 (ja) * | 2000-04-12 | 2013-06-26 | ファルマ・マール・ソシエダード・アノニマ | 抗腫瘍性エクチナサイジン誘導体 |
| MXPA02011319A (es) * | 2000-05-15 | 2003-06-06 | Pharma Mar Sa | Analogos antitumorales de ecteinascidina 743. |
-
2001
- 2001-08-07 GB GBGB0119243.4A patent/GB0119243D0/en not_active Ceased
-
2002
- 2002-08-06 EP EP02753134A patent/EP1414828B9/en not_active Expired - Lifetime
- 2002-08-06 EP EP07001308A patent/EP1806349A1/en not_active Ceased
- 2002-08-06 DK DK02753134T patent/DK1414828T3/da active
- 2002-08-06 CN CNB028196511A patent/CN100334094C/zh not_active Expired - Lifetime
- 2002-08-06 MX MXPA04001240A patent/MXPA04001240A/es active IP Right Grant
- 2002-08-06 WO PCT/GB2002/003592 patent/WO2003014127A1/en not_active Ceased
- 2002-08-06 CA CA2455768A patent/CA2455768C/en not_active Expired - Lifetime
- 2002-08-06 IL IL16005102A patent/IL160051A0/xx unknown
- 2002-08-06 AU AU2002313540A patent/AU2002313540B2/en active Active
- 2002-08-06 KR KR10-2004-7001924A patent/KR20040032150A/ko not_active Ceased
- 2002-08-06 DE DE60222775T patent/DE60222775T2/de not_active Expired - Lifetime
- 2002-08-06 ES ES02753134T patent/ES2294151T3/es not_active Expired - Lifetime
- 2002-08-06 PT PT02753134T patent/PT1414828E/pt unknown
- 2002-08-06 NZ NZ530837A patent/NZ530837A/en not_active IP Right Cessation
- 2002-08-06 JP JP2003519076A patent/JP4684552B2/ja not_active Expired - Lifetime
- 2002-08-06 HU HU0401174A patent/HU229779B1/hu unknown
- 2002-08-06 PL PL367940A patent/PL218295B1/pl unknown
- 2002-08-06 US US10/485,536 patent/US7763615B2/en active Active
- 2002-08-06 AT AT02753134T patent/ATE374777T1/de active
- 2002-08-06 RU RU2004106617/04A patent/RU2283842C2/ru active
- 2002-08-06 EP EP10180740A patent/EP2270018A1/en not_active Withdrawn
-
2004
- 2004-01-26 IL IL160051A patent/IL160051A/en active IP Right Grant
- 2004-03-05 NO NO20040961A patent/NO337476B1/no not_active IP Right Cessation
-
2007
- 2007-12-12 CY CY20071101576T patent/CY1107830T1/el unknown
-
2010
- 2010-09-17 JP JP2010209928A patent/JP2011026331A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992009607A1 (en) * | 1990-11-30 | 1992-06-11 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins 736 and 722 |
| WO2000018233A1 (en) * | 1998-09-30 | 2000-04-06 | President And Fellows Of Harvard College | Synthetic analogs of ecteinascidin-743 |
| WO2000069862A2 (en) * | 1999-05-14 | 2000-11-23 | Pharma Mar, S.A. | Hemisynthetic method and intermediates thereof |
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