HRP20110330T1 - Antitrombotski dvojni inhibitori, koji sadrže biotinski ostatak - Google Patents
Antitrombotski dvojni inhibitori, koji sadrže biotinski ostatak Download PDFInfo
- Publication number
- HRP20110330T1 HRP20110330T1 HR20110330T HRP20110330T HRP20110330T1 HR P20110330 T1 HRP20110330 T1 HR P20110330T1 HR 20110330 T HR20110330 T HR 20110330T HR P20110330 T HRP20110330 T HR P20110330T HR P20110330 T1 HRP20110330 T1 HR P20110330T1
- Authority
- HR
- Croatia
- Prior art keywords
- residue
- compound according
- alkyl
- spacer
- compound
- Prior art date
Links
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 title claims abstract 6
- 230000002785 anti-thrombosis Effects 0.000 title claims abstract 3
- 239000003146 anticoagulant agent Substances 0.000 title claims abstract 3
- 229960002685 biotin Drugs 0.000 title claims abstract 3
- 235000020958 biotin Nutrition 0.000 title claims abstract 3
- 239000011616 biotin Substances 0.000 title claims abstract 3
- 230000009977 dual effect Effects 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract 11
- 125000006850 spacer group Chemical group 0.000 claims abstract 8
- -1 1,2,3,4-tetrahydronaphthyl Chemical group 0.000 claims abstract 5
- 125000004429 atom Chemical group 0.000 claims abstract 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract 3
- 125000003277 amino group Chemical group 0.000 claims abstract 3
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims abstract 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 125000001424 substituent group Chemical group 0.000 claims abstract 3
- 230000001858 anti-Xa Effects 0.000 claims abstract 2
- 125000003118 aryl group Chemical group 0.000 claims abstract 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 2
- 230000000694 effects Effects 0.000 claims abstract 2
- 125000005842 heteroatom Chemical group 0.000 claims abstract 2
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 2
- 229920001542 oligosaccharide Polymers 0.000 claims abstract 2
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract 2
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical group NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- PCJFEVUKVKQSSL-UHFFFAOYSA-N 2h-1,2,4-oxadiazol-5-one Chemical group O=C1N=CNO1 PCJFEVUKVKQSSL-UHFFFAOYSA-N 0.000 claims 1
- 108090000190 Thrombin Proteins 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 150000001615 biotins Chemical class 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 239000002243 precursor Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 229960004072 thrombin Drugs 0.000 claims 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical group C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 abstract 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- 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
- A61K47/61—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 the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/66—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 a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/66—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 a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
- A61K47/665—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 a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells the pre-targeting system, clearing therapy or rescue therapy involving biotin-(strept) avidin systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- 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
-
- 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
-
- 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
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nanotechnology (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Surgery (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Antitrombotski spoj formule (I) oligosaharid-razmaknica-A (I), naznačen time što oligosaharid je negativno nabijeni pentasaharidni ostatak Formule (II) gdje R5 je OSO3- ili (1-8C)alkoksi, gdje naboj kompenziraju pozitivno nabijeni protuioni, te gdje se pentasaharidni ostatak dobiva iz pentasaharida koji ima (uz posredstvo AT-III) anti-Xa aktivnost kao takav; razmaknica je uglavnom farmakološki inaktivni fleksibilni vežući ostatak, s lancem dugim 10 do 70 atoma; A je ostatak -CH[NH-SO2-R1][CO-NR2-CH(4-benzamidin)-CO-NR3R4],gdje R1 je fenilna, naftilna, 1,2,3,4-tetrahidronaftilna, (izo)kinolinilna, tetrahidro(izo)kinolinilna, 3,4-dihidro-1H-izokinolinilna, kromanilna ili kamforska skupina, gdje navedene skupine mogu izborno biti supstituirane s jednim ili više supstituenata, koje se bira između (1-8C)alkila ili (1-8C)alkoksi; te gdjeR2 i R3 su neovisno H ili (1-8C)alkil; R4 je (1-8C)alkil ili (3-8C)cikloalkil; iliR3 i R4, zajedno s atomom dušika na kojeg su vezani, su nearomatski (4-8)eročlani prsten, koji izborno sadrži daljnji heteroatom, a navedeni prsten je izborno supstituiran s (1-8C)alkilom ili SO2-(1-8C)alkilom; ili njegova farmaceutski prihvatljiva sol, ili njegov derivat, gdje je amino skupina u amidino ostatku zaštićena hidroksilnom ili (1-6C)alkoksikarbonilnom skupinom; gdje razmaknica u spoju formule I dodatno sadrži najmanje jednu kovalentnu vezu s biotinskim ostatkom. Patent sadrži još 16 patentnih zahtjeva.
Claims (17)
1. Antitrombotski spoj formule (I)
oligosaharid-razmaknica-A (I),
naznačen time što oligosaharid je negativno nabijeni pentasaharidni ostatak Formule (II)
[image]
gdje R5 je OSO3– ili (1-8C)alkoksi, gdje naboj kompenziraju pozitivno nabijeni protuioni, te gdje se pentasaharidni ostatak dobiva iz pentasaharida koji ima (uz posredstvo AT-III) anti-Xa aktivnost kao takav;
razmaknica je uglavnom farmakološki inaktivni fleksibilni vežući ostatak, s lancem dugim 10 do 70 atoma;
A je ostatak -CH[NH-SO2-R1][CO-NR2-CH(4-benzamidin)-CO-NR3R4],
gdje R1 je fenilna, naftilna, 1,2,3,4-tetrahidronaftilna, (izo)kinolinilna, tetrahidro(izo)kinolinilna, 3,4-dihidro-1H-izokinolinilna, kromanilna ili kamforska skupina, gdje navedene skupine mogu izborno biti supstituirane s jednim ili više supstituenata, koje se bira između (1-8C)alkila ili (1-8C)alkoksi; te gdje
R2 i R3 su neovisno H ili (1-8C)alkil;
R4 je (1-8C)alkil ili (3-8C)cikloalkil; ili
R3 i R4, zajedno s atomom dušika na kojeg su vezani, su nearomatski (4-8)eročlani prsten, koji izborno sadrži daljnji heteroatom, a navedeni prsten je izborno supstituiran s (1-8C)alkilom ili SO2-(1-8C)alkilom;
ili njegova farmaceutski prihvatljiva sol, ili njegov derivat, gdje je amino skupina u amidino ostatku zaštićena hidroksilnom ili (1-6C)alkoksikarbonilnom skupinom;
gdje razmaknica u spoju formule I dodatno sadrži najmanje jednu kovalentnu vezu s biotinskim ostatkom.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što pentasaharidni ostatak ima strukturu
[image]
gdje R5 je OCH3 ili OSO3–.
3. Spoj u skladu s patentnim zahtjevom 2, naznačen time što pentasaharidni ostatak ima strukturu
[image]
4. Spoj bilo koji od patentnih zahtjeva 1 do 3, naznačen time što razmaknica je duga 10-50 atoma, po mogućnosti 16-22, a najpoželjnije 19 atoma.
5. Spoj u skladu s patentnim zahtjevom 4, naznačen time što razmaknica je duga 16-22 atoma.
6. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time što razmaknica sadrži najmanje jedan -(CH2CH2O)- element.
7. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time što R1 je fenil ili naftil, izborno supstituiran s jednim ili više supstituenata, koje se bira između metila ili metoksi.
8. Spoj u skladu s patentnim zahtjevom 7, naznačen time što R1 je 4-metoksi-2,3,6-trimetilfenil.
9. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačen time što NR3R4 predstavlja piperidinilnu skupinu.
10. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 9, naznačen time što R2 je H.
11. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačen time što razmaknica u spoju formule I sadrži jednu kovalentnu vezu s ostatkom biotinskog analoga formule -(CH2)4-NR-BT, gdje R je H ili (1-4C)alkil, a BT je ostatak
[image]
.
12. Spoj u skladu s patentnim zahtjevom 11, naznačen time što je
[image]
ili njegova farmaceutski prihvatljiva sol, ili njegov derivat, gdje je amino skupina u amidino ostatku zaštićena hidroksilnom ili (1-6C)alkoksikarbonilnom skupinom.
13. Spoj u skladu s patentnim zahtjevom 12, naznačen time što je u obliku svoje soli s natrijem.
14. Farmaceutski pripravak, naznačen time što sadrži spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 13 i farmaceutski prikladne pomoćne tvari.
15. Postupak dobivanja spoja formule I u skladu s patentnim zahtjevom 1, naznačen time što se sastoji u koraku u kojem je benzamidinski ostatak u ostatku A u obliku preteče, kao 1,2,4-oksadiazolin-5-onska skupina, i naknadno se prevodi u benzamidin skidanjem zaštite.
16. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 13, naznačen time što je namijenjen upotrebi u terapiji.
17. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 21, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje ili sprječavanje tromboze ili drugih bolesti povezanih s trombinom.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04106964 | 2004-12-23 | ||
| PCT/EP2005/057011 WO2006067173A2 (en) | 2004-12-23 | 2005-12-21 | Antithrombotic dual inhibitors comprising a biotin residue |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20110330T1 true HRP20110330T1 (hr) | 2011-06-30 |
Family
ID=35160114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20110330T HRP20110330T1 (hr) | 2004-12-23 | 2011-05-06 | Antitrombotski dvojni inhibitori, koji sadrže biotinski ostatak |
Country Status (29)
| Country | Link |
|---|---|
| US (3) | US8168595B2 (hr) |
| EP (1) | EP1830887B1 (hr) |
| JP (2) | JP5130051B2 (hr) |
| KR (1) | KR101284922B1 (hr) |
| CN (1) | CN101087622A (hr) |
| AR (1) | AR053657A1 (hr) |
| AT (1) | ATE500846T1 (hr) |
| AU (1) | AU2005318134B2 (hr) |
| BR (1) | BRPI0518560A2 (hr) |
| CA (1) | CA2592436C (hr) |
| DE (1) | DE602005026859D1 (hr) |
| DK (1) | DK1830887T3 (hr) |
| ES (1) | ES2361921T3 (hr) |
| HK (1) | HK1106712A1 (hr) |
| HR (1) | HRP20110330T1 (hr) |
| IL (2) | IL183713A (hr) |
| MX (1) | MX2007007837A (hr) |
| MY (1) | MY146121A (hr) |
| NO (1) | NO20072878L (hr) |
| NZ (1) | NZ555739A (hr) |
| PE (1) | PE20060773A1 (hr) |
| PL (1) | PL1830887T3 (hr) |
| PT (1) | PT1830887E (hr) |
| RU (1) | RU2403259C2 (hr) |
| SI (1) | SI1830887T1 (hr) |
| TW (1) | TWI403334B (hr) |
| UA (1) | UA88793C2 (hr) |
| WO (1) | WO2006067173A2 (hr) |
| ZA (1) | ZA200705088B (hr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI403334B (zh) * | 2004-12-23 | 2013-08-01 | Merck Sharp & Dohme | 包含生物素殘基之抗血栓雙重抑制劑 |
| CA2784529C (en) | 2009-12-18 | 2018-05-22 | Catalent France Beinheim Sa | Pharmaceutical oral dosage form containing a synthetic oligosaccharide |
| FR2974478A1 (fr) | 2011-04-28 | 2012-11-02 | Endotis Pharma | Conjugues d'oligosaccharides en prevention des lesions d'ischemie-reperfusion |
| ES2560467T3 (es) | 2011-06-17 | 2016-02-19 | Carbomimetics | Pentasacáridos sintéticos que tienen vida media corta y alta actividad |
| WO2013007762A1 (en) | 2011-07-11 | 2013-01-17 | Endotis Pharma | Combination of an anticoagulant and avidin useful in surgical intervention and clinical procedure |
| US10660973B2 (en) | 2015-04-28 | 2020-05-26 | Duke University | Thrombus imaging aptamers and methods of using same |
| CN109982707A (zh) | 2016-09-16 | 2019-07-05 | 杜克大学 | 血管性血友病因子（vwf）靶向剂及其使用方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4252951A (en) * | 1979-10-09 | 1981-02-24 | Eli Lilly And Company | Isolation of syn-7-(2-amino-4-thiazolyl)-(methoxyimino)acetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid |
| EP0454220B1 (en) | 1990-04-23 | 1993-08-18 | Akzo Nobel N.V. | Carbohydrate derivatives comprising a trisaccharide unit |
| IL102758A (en) | 1991-08-23 | 1997-03-18 | Akzo Nv | Glycosaminoglycanoid derivatives, their preparation and pharmaceutical compositions comprising them |
| ES2147216T3 (es) | 1993-09-01 | 2000-09-01 | Akzo Nobel Nv | Bisconjugados que comprenden dos sacaridos y un grupo de union. |
| FR2749849B1 (fr) * | 1996-06-14 | 1998-09-04 | Sanofi Sa | Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant |
| FR2751334B1 (fr) * | 1996-07-19 | 1998-10-16 | Sanofi Sa | Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant |
| FR2773804B1 (fr) * | 1998-01-19 | 2000-02-18 | Sanofi Sa | Polysaccharides de synthese, procede pour leur preparation et compositions pharmaceutiques le contenant |
| FR2773801B1 (fr) * | 1998-01-19 | 2000-05-12 | Sanofi Sa | Nouveaux pentasaccharides, procedes pour leurs preparations et compositions pharmaceutiques les contenant |
| BR9911300A (pt) * | 1998-06-17 | 2001-04-03 | Akzo Nobel Nv | Composto, composição farmacêutica, e, uso do composto |
| TWI289566B (en) * | 1999-12-07 | 2007-11-11 | N.V.Organon | Antithrombotic compound |
| FR2814463B1 (fr) * | 2000-09-22 | 2002-11-15 | Sanofi Synthelabo | Nouveaux polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine |
| TWI403334B (zh) * | 2004-12-23 | 2013-08-01 | Merck Sharp & Dohme | 包含生物素殘基之抗血栓雙重抑制劑 |
| ES2362011T3 (es) * | 2005-10-10 | 2011-06-27 | N.V. Organon | Inhibidores duales antitrombóticos anticoagulantes que comprenden una marca de biotina. |
-
2005
- 2005-12-14 TW TW094144361A patent/TWI403334B/zh not_active IP Right Cessation
- 2005-12-16 PE PE2005001503A patent/PE20060773A1/es not_active Application Discontinuation
- 2005-12-20 MY MYPI20056026A patent/MY146121A/en unknown
- 2005-12-21 CN CNA2005800444919A patent/CN101087622A/zh active Pending
- 2005-12-21 WO PCT/EP2005/057011 patent/WO2006067173A2/en active Application Filing
- 2005-12-21 MX MX2007007837A patent/MX2007007837A/es active IP Right Grant
- 2005-12-21 PL PL05821769T patent/PL1830887T3/pl unknown
- 2005-12-21 UA UAA200706654A patent/UA88793C2/ru unknown
- 2005-12-21 BR BRPI0518560-2A patent/BRPI0518560A2/pt not_active IP Right Cessation
- 2005-12-21 ES ES05821769T patent/ES2361921T3/es active Active
- 2005-12-21 KR KR1020077017005A patent/KR101284922B1/ko not_active IP Right Cessation
- 2005-12-21 AU AU2005318134A patent/AU2005318134B2/en active Active
- 2005-12-21 DK DK05821769.6T patent/DK1830887T3/da active
- 2005-12-21 DE DE602005026859T patent/DE602005026859D1/de active Active
- 2005-12-21 NZ NZ555739A patent/NZ555739A/en not_active IP Right Cessation
- 2005-12-21 CA CA2592436A patent/CA2592436C/en active Active
- 2005-12-21 SI SI200531279T patent/SI1830887T1/sl unknown
- 2005-12-21 PT PT05821769T patent/PT1830887E/pt unknown
- 2005-12-21 RU RU2007127859/04A patent/RU2403259C2/ru not_active IP Right Cessation
- 2005-12-21 AT AT05821769T patent/ATE500846T1/de active
- 2005-12-21 EP EP05821769A patent/EP1830887B1/en active Active
- 2005-12-21 JP JP2007547509A patent/JP5130051B2/ja active Active
- 2005-12-21 US US11/722,444 patent/US8168595B2/en active Active
- 2005-12-22 AR ARP050105472A patent/AR053657A1/es not_active Application Discontinuation
-
2007
- 2007-06-06 NO NO20072878A patent/NO20072878L/no not_active Application Discontinuation
- 2007-06-06 IL IL183713A patent/IL183713A/en not_active IP Right Cessation
- 2007-06-13 ZA ZA200705088A patent/ZA200705088B/xx unknown
-
2008
- 2008-01-10 HK HK08100324.9A patent/HK1106712A1/xx not_active IP Right Cessation
-
2011
- 2011-05-06 HR HR20110330T patent/HRP20110330T1/hr unknown
- 2011-12-18 IL IL217047A patent/IL217047A0/en unknown
-
2012
- 2012-04-04 US US13/438,905 patent/US8445450B2/en active Active
- 2012-04-04 US US13/439,012 patent/US20120238512A1/en not_active Abandoned
- 2012-09-14 JP JP2012202307A patent/JP5632886B2/ja active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20110330T1 (hr) | Antitrombotski dvojni inhibitori, koji sadrže biotinski ostatak | |
| EP3291815A1 (en) | Methods of treating a neurodegenerative disease | |
| CA2293415C (en) | Compositions for treating and preventing arterial thrombosis and use of a factor xa inhibitor on its own and/or combined with a platelet antiaggregating agent | |
| AR056786A1 (es) | Compuesto de 1h- imidazo ( 4,5-c) piridin-2-ilo, composicion farmaceutica que lo comprende, procedimiento para preparar dicha composicion, su uso para preparar unmedicamento, uso de una combinacion que omprende al compuesto y al menos un agente antineoplasico para preparar un medicamento y dicha com | |
| AR024060A1 (es) | Nuevos compuestos farmaceuticamente activos | |
| JP6010196B2 (ja) | オキサゾリジノン含有二量体化合物、組成物、ならびに作製および使用方法 | |
| MXPA01006474A (es) | Derivados colquinol como agentes perjudiciales vasculares. | |
| AR067181A1 (es) | Inhibidores de transcriptasa inversa de hiv, composicion farmaceutica, uso del compuesto para preparar un medicamento, agente de combinacion farmaceutica y metodo de inhibicion de la replicacion de un retrovirus | |
| WO2007042470A3 (en) | Antithrombotic compound | |
| NO20070837L (no) | Pyrido-pyrido pyrimidinderivater, fremstilling derav samt terapeutisk anvendelse for behandling av cancer. | |
| JP2012525437A5 (hr) | ||
| NZ508623A (en) | Antithrombotic peptide compounds with saccharide radicals | |
| JP2010535211A (ja) | 炎症性障害、脱髄障害および癌を治療するためのインダゾール化合物 | |
| HRP20110331T1 (hr) | Antikoagulantno-antitrombotski dvojni inhibitori, koji sadrže biotinski biljeg | |
| RU2001101556A (ru) | Антитромботические соединения | |
| FI104070B1 (fi) | Menetelmä terapeuttisesti käyttökelpoisten pyridiini- ja imidatsolijohdannaisten valmistamiseksi | |
| JP2007510653A5 (hr) | ||
| TWI492920B (zh) | 水楊酸苯胺衍生小分子之醫藥組合物及其製備與醫藥用途 | |
| BR0013375A (pt) | Composições farmacêuticas contendo derivados tiazolidinodiona e processo para sua preparação | |
| AR051319A1 (es) | Administracion pulmonar de un compuesto antitrombotico | |
| CZ290381B6 (cs) | Farmaceutický přípravek | |
| MEP1108A (en) | Use of specific dose of fondaparinux sodium for the treatment of acs | |
| RU2005128829A (ru) | Обладающие противоопухолевым действием 2-замещенные 18а-гомоэстра-1, 3, 5( 10 )-триен-3-илсульфаматы | |
| JP2001081029A (ja) | テロメラーゼ阻害剤 | |
| JP2002541257A5 (hr) |