DE69427799T2 - Anthracycline konjugate, deren herstellung und deren verwendung als antitumorwirkstoffe - Google Patents
Anthracycline konjugate, deren herstellung und deren verwendung als antitumorwirkstoffeInfo
- Publication number
- DE69427799T2 DE69427799T2 DE69427799T DE69427799T DE69427799T2 DE 69427799 T2 DE69427799 T2 DE 69427799T2 DE 69427799 T DE69427799 T DE 69427799T DE 69427799 T DE69427799 T DE 69427799T DE 69427799 T2 DE69427799 T2 DE 69427799T2
- Authority
- DE
- Germany
- Prior art keywords
- anthracycline
- formula
- polymer
- gly
- mol
- 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 - Fee Related
Links
- 229940045799 anthracyclines and related substance Drugs 0.000 title claims abstract description 76
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 239000013543 active substance Substances 0.000 title 1
- 229920000642 polymer Polymers 0.000 claims abstract description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 15
- 229940126575 aminoglycoside Drugs 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000006850 spacer group Chemical group 0.000 claims abstract description 10
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 2
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- 150000001875 compounds Chemical class 0.000 claims description 31
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- IBZGBXXTIGCACK-CWKPULSASA-N Adriamycinone Chemical compound C1[C@@](O)(C(=O)CO)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O IBZGBXXTIGCACK-CWKPULSASA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- JVHPTYWUBOQMBP-RVFAQHLVSA-N Idarubicin hydrochloride Chemical compound Cl.C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 JVHPTYWUBOQMBP-RVFAQHLVSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical group OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- BSEQCQPIMRQYKE-UHFFFAOYSA-N ethanol;2-methylprop-2-enamide Chemical compound CCO.CC(=C)C(N)=O BSEQCQPIMRQYKE-UHFFFAOYSA-N 0.000 description 1
- OYWHBKWUSRKKLT-QRPNPIFTSA-N ethyl 2-[[(2s)-2-amino-4-methylpentanoyl]amino]acetate;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CCOC(=O)CNC(=O)[C@@H](N)CC(C)C OYWHBKWUSRKKLT-QRPNPIFTSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- VHRYZQNGTZXDNX-UHFFFAOYSA-N methacryloyl chloride Chemical compound CC(=C)C(Cl)=O VHRYZQNGTZXDNX-UHFFFAOYSA-N 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Polyamides (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939309663A GB9309663D0 (en) | 1993-05-11 | 1993-05-11 | Biologically active compounds |
| PCT/EP1994/001100 WO1994026311A1 (en) | 1993-05-11 | 1994-04-08 | Anthracycline conjugates, their preparation and their use as antitumor agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69427799D1 DE69427799D1 (de) | 2001-08-30 |
| DE69427799T2 true DE69427799T2 (de) | 2002-05-02 |
Family
ID=10735264
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69427799T Expired - Fee Related DE69427799T2 (de) | 1993-05-11 | 1994-04-08 | Anthracycline konjugate, deren herstellung und deren verwendung als antitumorwirkstoffe |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US5571785A (https=) |
| EP (1) | EP0649312B1 (https=) |
| JP (1) | JPH08502519A (https=) |
| KR (1) | KR100330635B1 (https=) |
| CN (1) | CN1098106C (https=) |
| AT (1) | ATE203414T1 (https=) |
| AU (1) | AU671741B2 (https=) |
| CA (1) | CA2136438C (https=) |
| DE (1) | DE69427799T2 (https=) |
| DK (1) | DK0649312T3 (https=) |
| ES (1) | ES2161764T3 (https=) |
| FI (1) | FI112602B (https=) |
| GB (1) | GB9309663D0 (https=) |
| GR (1) | GR3036978T3 (https=) |
| HU (2) | HUT70509A (https=) |
| IL (1) | IL109528A (https=) |
| MY (1) | MY110974A (https=) |
| NZ (1) | NZ265266A (https=) |
| PL (1) | PL175325B1 (https=) |
| PT (1) | PT649312E (https=) |
| RU (1) | RU2145965C1 (https=) |
| TW (1) | TW268015B (https=) |
| UA (1) | UA42695C2 (https=) |
| WO (1) | WO1994026311A1 (https=) |
| ZA (1) | ZA943212B (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9320781D0 (en) * | 1993-10-08 | 1993-12-01 | Erba Carlo Spa | Polymer-bound camptothecin derivatives |
| GB9721069D0 (en) | 1997-10-03 | 1997-12-03 | Pharmacia & Upjohn Spa | Polymeric derivatives of camptothecin |
| GB9721070D0 (en) | 1997-10-03 | 1997-12-03 | Pharmacia & Upjohn Spa | Bioactive derivatives of camptothecin |
| EP1401875A4 (en) * | 2001-05-04 | 2005-01-26 | Univ Utah Res Found | HYALURONIC ACID-CONTAINING BIOKON JUGATES: TARGETED DELIVERY OF ANTIBODIES TO CANCER CELLS |
| WO2003037915A1 (en) * | 2001-10-31 | 2003-05-08 | Biopolymed Inc. | Biocompatible polymers including peptide spacer |
| US20050169883A1 (en) * | 2002-05-06 | 2005-08-04 | Prestwich Glenn D. | Preblocking with non-ha gags increases effectiveness of ha conjugated anticancer agents |
| WO2005004805A2 (en) * | 2003-07-02 | 2005-01-20 | Solux Corporation | Thermally stable crystalline epirubicin hydrochloride and method of making the same |
| US9737556B2 (en) | 2014-06-13 | 2017-08-22 | Trustees Of Tufts College | FAP-activated therapeutic agents, and uses related thereto |
| JP6744826B2 (ja) | 2014-06-13 | 2020-08-19 | バック バイオサイエンシーズ, エルエルシーBach BioSciences, LLC | Ｆａｐ活性化治療剤及びそれに関連する使用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5162512A (en) * | 1982-03-09 | 1992-11-10 | Cytogen Corporation | Amine derivatives of anthracycline antibodies |
| JPS60246400A (ja) * | 1984-05-22 | 1985-12-06 | Ajinomoto Co Inc | アントラサイクリン系化合物及び制ガン剤 |
| GB8614323D0 (en) * | 1986-06-12 | 1986-07-16 | Erba Farmitalia | Anthracyclines |
| US5169937A (en) * | 1986-11-18 | 1992-12-08 | The Scripps Research Institute | Method for producing stable glycosylated hemoglobin |
| DE3722699A1 (de) * | 1987-07-09 | 1989-01-19 | Behringwerke Ag | Zytostatisch wirksame anthacyclin-konjugate |
| CA2014244A1 (en) * | 1989-04-13 | 1990-10-13 | Takeda Chemical Industries, Ltd. | Stabilized composition of anthracyclines |
| GB9017024D0 (en) * | 1990-08-03 | 1990-09-19 | Erba Carlo Spa | New linker for bioactive agents |
| GB9026491D0 (en) * | 1990-12-05 | 1991-01-23 | Erba Carlo Spa | Anthracycline-conjugates |
-
1993
- 1993-05-11 GB GB939309663A patent/GB9309663D0/en active Pending
-
1994
- 1994-04-08 DE DE69427799T patent/DE69427799T2/de not_active Expired - Fee Related
- 1994-04-08 HU HU9403811A patent/HUT70509A/hu unknown
- 1994-04-08 WO PCT/EP1994/001100 patent/WO1994026311A1/en not_active Ceased
- 1994-04-08 UA UA94129260A patent/UA42695C2/uk unknown
- 1994-04-08 RU RU94046336A patent/RU2145965C1/ru not_active IP Right Cessation
- 1994-04-08 AU AU65666/94A patent/AU671741B2/en not_active Ceased
- 1994-04-08 NZ NZ265266A patent/NZ265266A/en unknown
- 1994-04-08 KR KR1019940704830A patent/KR100330635B1/ko not_active Expired - Fee Related
- 1994-04-08 JP JP6524851A patent/JPH08502519A/ja not_active Ceased
- 1994-04-08 ES ES94913560T patent/ES2161764T3/es not_active Expired - Lifetime
- 1994-04-08 CA CA002136438A patent/CA2136438C/en not_active Expired - Fee Related
- 1994-04-08 EP EP94913560A patent/EP0649312B1/en not_active Expired - Lifetime
- 1994-04-08 PT PT94913560T patent/PT649312E/pt unknown
- 1994-04-08 US US08/351,474 patent/US5571785A/en not_active Expired - Fee Related
- 1994-04-08 CN CN94190242A patent/CN1098106C/zh not_active Expired - Fee Related
- 1994-04-08 DK DK94913560T patent/DK0649312T3/da active
- 1994-04-08 AT AT94913560T patent/ATE203414T1/de not_active IP Right Cessation
- 1994-04-08 PL PL94306861A patent/PL175325B1/pl not_active IP Right Cessation
- 1994-04-11 TW TW083103180A patent/TW268015B/zh active
- 1994-05-03 IL IL10952894A patent/IL109528A/en not_active IP Right Cessation
- 1994-05-09 ZA ZA943212A patent/ZA943212B/xx unknown
- 1994-05-09 MY MYPI94001149A patent/MY110974A/en unknown
- 1994-12-28 FI FI946128A patent/FI112602B/fi not_active IP Right Cessation
-
1995
- 1995-06-19 HU HU95P/P00250P patent/HU211538A9/hu unknown
-
2001
- 2001-10-22 GR GR20010401848T patent/GR3036978T3/el not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |