DE69936845T2 - Halbsynthetische ectein-ascidine - Google Patents
Halbsynthetische ectein-ascidine Download PDFInfo
- Publication number
- DE69936845T2 DE69936845T2 DE69936845T DE69936845T DE69936845T2 DE 69936845 T2 DE69936845 T2 DE 69936845T2 DE 69936845 T DE69936845 T DE 69936845T DE 69936845 T DE69936845 T DE 69936845T DE 69936845 T2 DE69936845 T2 DE 69936845T2
- Authority
- DE
- Germany
- Prior art keywords
- mammalian
- iso
- compound
- excipients
- tumor
- 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
- 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 title abstract description 17
- 229960000977 trabectedin Drugs 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 230000000259 anti-tumor effect Effects 0.000 claims description 6
- 208000032839 leukemia Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 201000005296 lung carcinoma Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- 230000000704 physical effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 241000798369 Ecteinascidia turbinata Species 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 3
- 238000002000 high resolution fast-atom bombardment mass spectrometry Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 208000001382 Experimental Melanoma Diseases 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 1
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 240000002044 Rhizophora apiculata Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000013415 human tumor xenograft model Methods 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Dental Preparations (AREA)
- Saccharide Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Separation Of Suspended Particles By Flocculating Agents (AREA)
- Peptides Or Proteins (AREA)
- Furan Compounds (AREA)
- Pyrane Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8080298P | 1998-04-06 | 1998-04-06 | |
| US80802P | 1998-04-06 | ||
| PCT/US1999/007471 WO1999051238A1 (en) | 1998-04-06 | 1999-04-05 | Semi-synthetic ecteinascidins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69936845D1 DE69936845D1 (de) | 2007-09-27 |
| DE69936845T2 true DE69936845T2 (de) | 2008-05-08 |
Family
ID=22159716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69936845T Expired - Lifetime DE69936845T2 (de) | 1998-04-06 | 1999-04-05 | Halbsynthetische ectein-ascidine |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US6124293A (enExample) |
| EP (2) | EP1876180A3 (enExample) |
| JP (1) | JP4443043B2 (enExample) |
| KR (1) | KR100603219B1 (enExample) |
| CN (1) | CN1157189C (enExample) |
| AT (1) | ATE370148T1 (enExample) |
| AU (1) | AU758100B2 (enExample) |
| BG (1) | BG65088B1 (enExample) |
| BR (1) | BR9909488B1 (enExample) |
| CA (1) | CA2327468C (enExample) |
| CY (1) | CY1106988T1 (enExample) |
| CZ (1) | CZ301083B6 (enExample) |
| DE (1) | DE69936845T2 (enExample) |
| DK (1) | DK1067933T3 (enExample) |
| ES (1) | ES2292237T3 (enExample) |
| HU (1) | HUP0104273A3 (enExample) |
| IL (2) | IL138856A0 (enExample) |
| MX (1) | MXPA00009840A (enExample) |
| NO (1) | NO328147B1 (enExample) |
| NZ (1) | NZ507350A (enExample) |
| PL (1) | PL196809B1 (enExample) |
| PT (1) | PT1067933E (enExample) |
| RU (1) | RU2217432C2 (enExample) |
| SK (1) | SK285669B6 (enExample) |
| TR (1) | TR200002921T2 (enExample) |
| UA (1) | UA59439C2 (enExample) |
| WO (1) | WO1999051238A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5985876A (en) * | 1997-04-15 | 1999-11-16 | Univ Illinois | Nucleophile substituted ecteinascidins and N-oxide ecteinascidins |
| CN1195514C (zh) * | 1998-05-11 | 2005-04-06 | 法马马有限公司 | 海鞘素 743的代谢物 |
| MY164077A (en) * | 1999-05-13 | 2017-11-30 | Pharma Mar Sa | Compositions and uses of et743 for treating cancer |
| MY130271A (en) | 1999-05-14 | 2007-06-29 | Pharma Mar Sa | Hemisynthetic method and new compounds |
| EP1254140A4 (en) | 2000-01-19 | 2003-03-12 | Univ Columbia | SAFRAMYCIN-ECTEINASCIDIN SERIES COMPOUNDS, USES AND SYNTHESIS |
| US7919493B2 (en) * | 2000-04-12 | 2011-04-05 | Pharma Mar, S.A. | Anititumoral ecteinascidin derivatives |
| MXPA02011319A (es) | 2000-05-15 | 2003-06-06 | Pharma Mar Sa | Analogos antitumorales de ecteinascidina 743. |
| EP1339713A2 (en) | 2000-11-03 | 2003-09-03 | President And Fellows Of Harvard College | Saframycins, analogues and uses thereof |
| US20040108086A1 (en) * | 2000-11-06 | 2004-06-10 | Naoto Takahashi | Effective antitumor treatments |
| GB0117402D0 (en) * | 2001-07-17 | 2001-09-05 | Pharma Mar Sa | New antitumoral derivatives of et-743 |
| GB0119243D0 (en) | 2001-08-07 | 2001-10-03 | Pharma Mar Sa | Antitumoral analogs of ET-743 |
| GB0202544D0 (en) * | 2002-02-04 | 2002-03-20 | Pharma Mar Sa | The synthesis of naturally occuring ecteinascidins and related compounds |
| GB0312407D0 (en) * | 2003-05-29 | 2003-07-02 | Pharma Mar Sau | Treatment |
| GB0324201D0 (en) * | 2003-10-15 | 2003-11-19 | Pharma Mar Sau | Improved antitumoral combinations |
| SI1689404T1 (sl) * | 2003-11-13 | 2009-02-28 | Pharma Mar Sau | Kombinacija et-743 s 5-fluorouracil pro zdravili za zdravljenje raka |
| US20080255132A1 (en) * | 2003-11-14 | 2008-10-16 | Eric Rowinsky | Combination Therapy Comprising the Use of Et-743 and Paclitaxel for Treating Cancer |
| GB0326486D0 (en) * | 2003-11-14 | 2003-12-17 | Pharma Mar Sau | Combination treatment |
| US20080293725A1 (en) * | 2004-07-09 | 2008-11-27 | Rafael Rosell Costa | Prognostic Molecular Markers |
| JP2008514688A (ja) * | 2004-09-29 | 2008-05-08 | ファルマ・マル・エス・アー， ソシエダッド・ユニペルソナル | 抗炎症剤としてのエクテイナシジン化合物 |
| HRP20090345T1 (en) * | 2004-10-26 | 2009-08-31 | Pharma Mar S.A. | Pegylated liposomal doxorubicin in combination with ecteinescidin 743 |
| RS50510B (sr) | 2004-10-29 | 2010-03-02 | Pharma Mar S.A., Sociedad Unipersonal | Formulacije koje sadrže ekteinascidin i disaharid |
| GB0522082D0 (en) * | 2005-10-31 | 2005-12-07 | Pharma Mar Sa | Formulations |
| CN100355775C (zh) * | 2006-01-20 | 2007-12-19 | 南方医科大学 | 一种海鞘多肽及其制备方法 |
| US20100267732A1 (en) * | 2007-10-19 | 2010-10-21 | Pharma Mar, S.A. | Prognostic Molecular Markers for ET-743 Treatment |
| KR102452022B1 (ko) | 2010-11-12 | 2022-10-06 | 파르마 마르 에스.에이. | 항종양 알칼로이드를 이용한 병용요법 |
| JP2019504061A (ja) * | 2016-02-04 | 2019-02-14 | ジエンス ヘンルイ メデイシンカンパニー リミテッドＪｉａｎｇｓｕ Ｈｅｎｇｒｕｉ Ｍｅｄｉｃｉｎｅ Ｃｏ．，Ｌｔｄ． | トラベクテジンの注射可能な胃腸外用医薬組成物及びその製造方法 |
| JOP20190254A1 (ar) | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | مركبات مضادة للأورام |
| PH12022551216A1 (en) | 2019-11-21 | 2023-07-17 | Pharma Mar Sa | Methods of treating small cell lung cancer with lurbinectedin formulations |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5089273A (en) * | 1986-06-09 | 1992-02-18 | Board Of Trustees Of The University Of Illinois | Ecteinascidins 729, 743, 745, 759A, 759B and 770 |
| US5149804A (en) * | 1990-11-30 | 1992-09-22 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins 736 and 722 |
| 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 |
| TW221441B (enExample) * | 1991-01-25 | 1994-03-01 | Taiho Pharmaceutical Co Ltd | |
| US5440055A (en) * | 1993-03-12 | 1995-08-08 | Aphios Corporation | Method and apparatus for extracting taxol from source materials |
| 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 |
-
1999
- 1999-04-05 CZ CZ20003650A patent/CZ301083B6/cs not_active IP Right Cessation
- 1999-04-05 AT AT99916379T patent/ATE370148T1/de not_active IP Right Cessation
- 1999-04-05 IL IL13885699A patent/IL138856A0/xx active IP Right Grant
- 1999-04-05 KR KR1020007011112A patent/KR100603219B1/ko not_active Expired - Fee Related
- 1999-04-05 JP JP2000542009A patent/JP4443043B2/ja not_active Expired - Fee Related
- 1999-04-05 NZ NZ507350A patent/NZ507350A/xx unknown
- 1999-04-05 TR TR2000/02921T patent/TR200002921T2/xx unknown
- 1999-04-05 PT PT99916379T patent/PT1067933E/pt unknown
- 1999-04-05 PL PL343439A patent/PL196809B1/pl not_active IP Right Cessation
- 1999-04-05 US US09/286,242 patent/US6124293A/en not_active Expired - Fee Related
- 1999-04-05 RU RU2000128058/04A patent/RU2217432C2/ru not_active IP Right Cessation
- 1999-04-05 EP EP07011035A patent/EP1876180A3/en not_active Withdrawn
- 1999-04-05 CA CA002327468A patent/CA2327468C/en not_active Expired - Fee Related
- 1999-04-05 AU AU34713/99A patent/AU758100B2/en not_active Ceased
- 1999-04-05 DE DE69936845T patent/DE69936845T2/de not_active Expired - Lifetime
- 1999-04-05 CN CNB998070769A patent/CN1157189C/zh not_active Expired - Fee Related
- 1999-04-05 ES ES99916379T patent/ES2292237T3/es not_active Expired - Lifetime
- 1999-04-05 SK SK1501-2000A patent/SK285669B6/sk not_active IP Right Cessation
- 1999-04-05 BR BRPI9909488-6A patent/BR9909488B1/pt not_active IP Right Cessation
- 1999-04-05 WO PCT/US1999/007471 patent/WO1999051238A1/en not_active Ceased
- 1999-04-05 DK DK99916379T patent/DK1067933T3/da active
- 1999-04-05 MX MXPA00009840A patent/MXPA00009840A/es active IP Right Grant
- 1999-04-05 EP EP99916379A patent/EP1067933B1/en not_active Expired - Lifetime
- 1999-04-05 HU HU0104273A patent/HUP0104273A3/hu unknown
- 1999-05-04 UA UA2000105674A patent/UA59439C2/uk unknown
-
2000
- 2000-10-03 NO NO20004978A patent/NO328147B1/no not_active IP Right Cessation
- 2000-10-04 IL IL138856A patent/IL138856A/en not_active IP Right Cessation
- 2000-11-02 BG BG104902A patent/BG65088B1/bg unknown
-
2007
- 2007-11-08 CY CY20071101439T patent/CY1106988T1/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |