DE10102878A1 - Oligo- oder Polyalkylengekoppelte Thrombininhibitoren - Google Patents
Oligo- oder Polyalkylengekoppelte ThrombininhibitorenInfo
- Publication number
- DE10102878A1 DE10102878A1 DE10102878A DE10102878A DE10102878A1 DE 10102878 A1 DE10102878 A1 DE 10102878A1 DE 10102878 A DE10102878 A DE 10102878A DE 10102878 A DE10102878 A DE 10102878A DE 10102878 A1 DE10102878 A1 DE 10102878A1
- Authority
- DE
- Germany
- Prior art keywords
- radical
- integer
- inhibitor
- alkyl
- pro
- 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.)
- Ceased
Links
- 229940122388 Thrombin inhibitor Drugs 0.000 title claims description 20
- 239000003868 thrombin inhibitor Substances 0.000 title claims description 20
- 229920001281 polyalkylene Polymers 0.000 title description 2
- 239000003112 inhibitor Substances 0.000 claims abstract description 49
- 229920001515 polyalkylene glycol Polymers 0.000 claims abstract description 22
- 230000001732 thrombotic effect Effects 0.000 claims abstract description 6
- 238000011321 prophylaxis Methods 0.000 claims abstract description 3
- -1 aralkyl radical Chemical class 0.000 claims description 73
- 229920001223 polyethylene glycol Polymers 0.000 claims description 66
- 150000001875 compounds Chemical class 0.000 claims description 56
- 150000003254 radicals Chemical class 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 claims description 8
- 230000008030 elimination Effects 0.000 claims description 8
- 238000003379 elimination reaction Methods 0.000 claims description 8
- 150000005840 aryl radicals Chemical class 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000003827 glycol group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 2
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 108090000190 Thrombin Proteins 0.000 abstract description 28
- 239000013543 active substance Substances 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000012622 synthetic inhibitor Substances 0.000 abstract description 2
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- 230000001933 haemocoagulation Effects 0.000 abstract 1
- 238000011282 treatment Methods 0.000 abstract 1
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 40
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- 229960004072 thrombin Drugs 0.000 description 25
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- 239000002904 solvent Substances 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 18
- 108090000631 Trypsin Proteins 0.000 description 17
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- 239000000047 product Substances 0.000 description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
- 239000012588 trypsin Substances 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- QUUYRYYUKNNNNS-UHFFFAOYSA-N piperidine-1-carboximidamide Chemical compound NC(=N)N1CCCCC1 QUUYRYYUKNNNNS-UHFFFAOYSA-N 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
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- 239000012043 crude product Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000012047 saturated solution Substances 0.000 description 6
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- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 5
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- 239000004926 polymethyl methacrylate Substances 0.000 description 5
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- 102000007625 Hirudins Human genes 0.000 description 4
- 108010007267 Hirudins Proteins 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- TUWZZXGAUMSUOB-UHFFFAOYSA-N benzyl piperidine-1-carboxylate Chemical compound C1CCCCN1C(=O)OCC1=CC=CC=C1 TUWZZXGAUMSUOB-UHFFFAOYSA-N 0.000 description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 150000003983 crown ethers Chemical class 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
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- 238000002360 preparation method Methods 0.000 description 4
- KWPACVJPAFGBEQ-IKGGRYGDSA-N (2s)-1-[(2r)-2-amino-3-phenylpropanoyl]-n-[(3s)-1-chloro-6-(diaminomethylideneamino)-2-oxohexan-3-yl]pyrrolidine-2-carboxamide Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)CCl)C1=CC=CC=C1 KWPACVJPAFGBEQ-IKGGRYGDSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- ABSNGNUGFQIDDO-UHFFFAOYSA-N 2-benzylguanidine Chemical compound NC(N)=NCC1=CC=CC=C1 ABSNGNUGFQIDDO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
-
- 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
- A61K47/59—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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Polymers & Plastics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Polyethers (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10102878A DE10102878A1 (de) | 2001-01-23 | 2001-01-23 | Oligo- oder Polyalkylengekoppelte Thrombininhibitoren |
| PCT/EP2002/000652 WO2002059065A2 (de) | 2001-01-23 | 2002-01-23 | Oligo- oder polyalkylenglycolgekoppelte thrombininhibitoren |
| DE50214734T DE50214734D1 (de) | 2001-01-23 | 2002-01-23 | Oligo- oder polyalkylenglycolgekoppelte thrombininhibitoren |
| JP2002559370A JP4461217B2 (ja) | 2001-01-23 | 2002-01-23 | オリゴまたはポリアルキレングリコール結合トロンビン阻害剤 |
| AT02708308T ATE485838T1 (de) | 2001-01-23 | 2002-01-23 | Oligo- oder polyalkylenglycolgekoppelte thrombininhibitoren |
| EP02708308A EP1355674B1 (de) | 2001-01-23 | 2002-01-23 | Oligo- oder polyalkylenglycolgekoppelte thrombininhibitoren |
| CA2431487A CA2431487C (en) | 2001-01-23 | 2002-01-23 | Oligo or polyalkylene glycol-coupled thrombin inhibitors |
| US10/344,722 US7407982B2 (en) | 2001-01-23 | 2002-01-23 | Oligo or polyalkylene glycol-coupled thrombin inhibitors |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10102878A DE10102878A1 (de) | 2001-01-23 | 2001-01-23 | Oligo- oder Polyalkylengekoppelte Thrombininhibitoren |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10102878A1 true DE10102878A1 (de) | 2002-08-01 |
Family
ID=7671444
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10102878A Ceased DE10102878A1 (de) | 2001-01-23 | 2001-01-23 | Oligo- oder Polyalkylengekoppelte Thrombininhibitoren |
| DE50214734T Expired - Lifetime DE50214734D1 (de) | 2001-01-23 | 2002-01-23 | Oligo- oder polyalkylenglycolgekoppelte thrombininhibitoren |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE50214734T Expired - Lifetime DE50214734D1 (de) | 2001-01-23 | 2002-01-23 | Oligo- oder polyalkylenglycolgekoppelte thrombininhibitoren |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7407982B2 (https=) |
| EP (1) | EP1355674B1 (https=) |
| JP (1) | JP4461217B2 (https=) |
| AT (1) | ATE485838T1 (https=) |
| CA (1) | CA2431487C (https=) |
| DE (2) | DE10102878A1 (https=) |
| WO (1) | WO2002059065A2 (https=) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003051399A3 (de) * | 2001-12-19 | 2003-09-25 | Goetz Nowak | Verwendung von molekulargewichtsenweiterten substanzen in der tumortheraphie |
| DE102007033787A1 (de) | 2007-07-09 | 2009-01-15 | Aesculap Ag | Gefäßprothese mit reduzierter Thrombogenität |
| WO2010033226A1 (en) * | 2008-09-17 | 2010-03-25 | Nektar Therapeutics | Oligomer-protease inhibitor conjugates |
| EP2340822A1 (de) * | 2003-01-15 | 2011-07-06 | The Medicines Company (Leipzig) GmbH | Acylierte 4-Amidino- und 4-Guanidinobenzylaminen zur Inhibierung von Plasmakallikrein |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7838560B2 (en) * | 2002-03-11 | 2010-11-23 | The Medicines Company (Leipzig) Gmbh | Urokinase inhibitors, production and use thereof |
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| DE102006048300A1 (de) | 2006-01-26 | 2007-08-02 | Hellstern, Peter, Prof. Dr.med. | Inhibitoren des Blutgerinnungsfaktors Xa zur Verwendung als Antikoagulans |
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| JP6863295B2 (ja) | 2016-10-07 | 2021-04-21 | 東レ株式会社 | 筒状織物 |
| CA3058121A1 (en) | 2017-03-31 | 2018-10-04 | Toray Industries, Inc. | Cylindrical structure |
| CN117497842B (zh) * | 2023-12-27 | 2024-03-12 | 江苏蓝固新能源科技有限公司 | 一种聚合物电解质和制备方法及其在二次电池中的应用 |
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| WO1991008229A1 (de) | 1989-12-01 | 1991-06-13 | Basf Aktiengesellschaft | Hirudinpolyalkylenglykolkonjugate |
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| US5798377A (en) * | 1996-10-21 | 1998-08-25 | Merck & Co., Inc. | Thrombin inhibitors |
| DE69800640T2 (de) * | 1997-01-29 | 2001-07-05 | Polymasc Pharmaceuticals Plc, London | Pegylationsverfahren |
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2002
- 2002-01-23 CA CA2431487A patent/CA2431487C/en not_active Expired - Fee Related
- 2002-01-23 JP JP2002559370A patent/JP4461217B2/ja not_active Expired - Fee Related
- 2002-01-23 AT AT02708308T patent/ATE485838T1/de active
- 2002-01-23 WO PCT/EP2002/000652 patent/WO2002059065A2/de not_active Ceased
- 2002-01-23 DE DE50214734T patent/DE50214734D1/de not_active Expired - Lifetime
- 2002-01-23 US US10/344,722 patent/US7407982B2/en not_active Expired - Fee Related
- 2002-01-23 EP EP02708308A patent/EP1355674B1/de not_active Expired - Lifetime
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| EP0658585A2 (de) * | 1993-12-10 | 1995-06-21 | BEHRINGWERKE Aktiengesellschaft | Amidinophenylalaninderivate, Verfahren zu deren Herstellung, deren Verwendung und diese enthaltende Mittel als Antikoagulantien |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003051399A3 (de) * | 2001-12-19 | 2003-09-25 | Goetz Nowak | Verwendung von molekulargewichtsenweiterten substanzen in der tumortheraphie |
| EP2340822A1 (de) * | 2003-01-15 | 2011-07-06 | The Medicines Company (Leipzig) GmbH | Acylierte 4-Amidino- und 4-Guanidinobenzylaminen zur Inhibierung von Plasmakallikrein |
| EP1583526B1 (de) * | 2003-01-15 | 2012-09-05 | The Medicines Company (Leipzig) GmbH | Acylierte 4-amidino- und 4-guanidinobenzylaminen zur inhibierung von plasmakallikrein |
| US9365613B2 (en) | 2003-01-15 | 2016-06-14 | The Medicines Company (Leipzig) Gmbh | Acylated 4-amidino- and -4-guanidinobenzylamines for inhibition of plasma kallikrein |
| DE102007033787A1 (de) | 2007-07-09 | 2009-01-15 | Aesculap Ag | Gefäßprothese mit reduzierter Thrombogenität |
| WO2010033226A1 (en) * | 2008-09-17 | 2010-03-25 | Nektar Therapeutics | Oligomer-protease inhibitor conjugates |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1355674A2 (de) | 2003-10-29 |
| US20050070479A1 (en) | 2005-03-31 |
| JP4461217B2 (ja) | 2010-05-12 |
| JP2004525888A (ja) | 2004-08-26 |
| WO2002059065A2 (de) | 2002-08-01 |
| WO2002059065A3 (de) | 2002-12-12 |
| EP1355674B1 (de) | 2010-10-27 |
| CA2431487C (en) | 2012-03-27 |
| ATE485838T1 (de) | 2010-11-15 |
| DE50214734D1 (de) | 2010-12-09 |
| CA2431487A1 (en) | 2002-08-01 |
| US7407982B2 (en) | 2008-08-05 |
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