HRP20030017A2 - Thrombin inhibitors comprising an aminoisoquinoline group - Google Patents
Thrombin inhibitors comprising an aminoisoquinoline group Download PDFInfo
- Publication number
- HRP20030017A2 HRP20030017A2 HR20030017A HRP20030017A HRP20030017A2 HR P20030017 A2 HRP20030017 A2 HR P20030017A2 HR 20030017 A HR20030017 A HR 20030017A HR P20030017 A HRP20030017 A HR P20030017A HR P20030017 A2 HRP20030017 A2 HR P20030017A2
- Authority
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- Croatia
- Prior art keywords
- cyclohexyl
- compounds
- amino
- compound
- solution
- Prior art date
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- 239000003868 thrombin inhibitor Substances 0.000 title description 10
- 229940122388 Thrombin inhibitor Drugs 0.000 title description 9
- OSILBMSORKFRTB-UHFFFAOYSA-N isoquinolin-1-amine Chemical group C1=CC=C2C(N)=NC=CC2=C1 OSILBMSORKFRTB-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 61
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 12
- 108090000190 Thrombin Proteins 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 229960004072 thrombin Drugs 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- -1 2-(1H-benzotriazole- 1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate Chemical compound 0.000 description 24
- 239000000243 solution Substances 0.000 description 20
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- 239000000203 mixture Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 238000000034 method Methods 0.000 description 12
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- 239000000872 buffer Substances 0.000 description 10
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 10
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- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
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- 230000002378 acidificating effect Effects 0.000 description 5
- 239000004019 antithrombin Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- BIXDBUPMYYSVJW-UHFFFAOYSA-N 6-methoxy-3-methylisoquinolin-1-amine Chemical compound NC1=NC(C)=CC2=CC(OC)=CC=C21 BIXDBUPMYYSVJW-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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- 238000002360 preparation method Methods 0.000 description 4
- WXKPEOSDDROAEB-UHFFFAOYSA-N 6-(aminomethyl)-3-methylisoquinolin-1-amine Chemical compound NCC1=CC=C2C(N)=NC(C)=CC2=C1 WXKPEOSDDROAEB-UHFFFAOYSA-N 0.000 description 3
- LWDVTRXNUGVQES-UHFFFAOYSA-N 6-(aminomethyl)isoquinolin-1-amine Chemical compound NC1=NC=CC2=CC(CN)=CC=C21 LWDVTRXNUGVQES-UHFFFAOYSA-N 0.000 description 3
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 239000012317 TBTU Substances 0.000 description 3
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
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- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
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- RMMRRRLPDBJBQL-UHFFFAOYSA-N 1-(3-methoxyphenyl)propan-2-one Chemical compound COC1=CC=CC(CC(C)=O)=C1 RMMRRRLPDBJBQL-UHFFFAOYSA-N 0.000 description 2
- WHWXEUUKHBARIS-UHFFFAOYSA-N 1-amino-3-methylisoquinolin-6-ol Chemical compound OC1=CC=C2C(N)=NC(C)=CC2=C1 WHWXEUUKHBARIS-UHFFFAOYSA-N 0.000 description 2
- MJGXIHYQQLOPFF-UHFFFAOYSA-N 1-amino-3-methylisoquinoline-6-carbonitrile Chemical compound N#CC1=CC=C2C(N)=NC(C)=CC2=C1 MJGXIHYQQLOPFF-UHFFFAOYSA-N 0.000 description 2
- XZWWZXOLGNSYLC-UHFFFAOYSA-N 6-(aminomethyl)-3-methylisoquinolin-1-amine;hydrochloride Chemical compound Cl.NCC1=CC=C2C(N)=NC(C)=CC2=C1 XZWWZXOLGNSYLC-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
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- 125000001769 aryl amino group Chemical group 0.000 description 2
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- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 description 2
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000001913 cellulose Chemical class 0.000 description 1
- 229920002678 cellulose Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000011874 heated mixture Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920005596 polymer binder Polymers 0.000 description 1
- 239000002491 polymer binding agent Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000003331 prothrombotic effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000008107 starch Chemical class 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 201000005060 thrombophlebitis Diseases 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 230000018889 transepithelial transport Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00202491 | 2000-07-12 | ||
| PCT/EP2001/007887 WO2002004423A1 (en) | 2000-07-12 | 2001-07-09 | Thrombin inhibitors comprising an aminoisoquinoline group |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20030017A2 true HRP20030017A2 (en) | 2003-04-30 |
Family
ID=8171793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20030017A HRP20030017A2 (en) | 2000-07-12 | 2003-01-10 | Thrombin inhibitors comprising an aminoisoquinoline group |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6642253B2 (ko) |
| EP (1) | EP1303491A1 (ko) |
| JP (1) | JP2004502759A (ko) |
| KR (1) | KR20030022270A (ko) |
| CN (1) | CN1441784A (ko) |
| AR (1) | AR029596A1 (ko) |
| AU (1) | AU2001278476A1 (ko) |
| BR (1) | BR0112338A (ko) |
| CA (1) | CA2413035A1 (ko) |
| CZ (1) | CZ200392A3 (ko) |
| EC (1) | ECSP034422A (ko) |
| HR (1) | HRP20030017A2 (ko) |
| HU (1) | HUP0301258A2 (ko) |
| IL (1) | IL153611A0 (ko) |
| MX (1) | MXPA03000337A (ko) |
| NO (1) | NO20030145L (ko) |
| NZ (1) | NZ523553A (ko) |
| PE (1) | PE20020209A1 (ko) |
| PL (1) | PL359787A1 (ko) |
| RU (1) | RU2003104017A (ko) |
| SK (1) | SK322003A3 (ko) |
| WO (1) | WO2002004423A1 (ko) |
| ZA (1) | ZA200300080B (ko) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6642252B2 (en) | 2000-11-07 | 2003-11-04 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
| US6906192B2 (en) | 2000-11-07 | 2005-06-14 | Bristol Myers Squibb Company | Processes for the preparation of acid derivatives useful as serine protease inhibitors |
| TWI389899B (zh) * | 2006-08-08 | 2013-03-21 | Msd Oss Bv | 具口服活性之凝血酶抑制劑 |
| PT2102164E (pt) * | 2006-12-27 | 2011-01-21 | Sanofi Aventis | Derivados de isoquinolina e de isoquinolinona substituída com cicloalquilamina |
| US7927378B2 (en) * | 2007-03-05 | 2011-04-19 | Scussel Sbj Systems, Llc | Vacuum assisted prosthetic sleeve and socket |
| CN109810172B (zh) * | 2017-11-21 | 2021-01-01 | 首都医科大学 | 异喹啉-3-甲酰-PARGD(aa)aa,其制备,抗静脉血栓活性和应用 |
| CN109810173B (zh) * | 2017-11-21 | 2020-11-27 | 首都医科大学 | 二氢异喹啉-3-甲酰-TARGD(aa)aa,其制备,抗静脉血栓活性和应用 |
| CN109810174B (zh) * | 2017-11-21 | 2021-01-01 | 首都医科大学 | 异喹啉-3-甲酰-TARGD(aa)aa,其制备,抗静脉血栓活性和应用 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL123986A (en) | 1997-04-24 | 2011-10-31 | Organon Nv | Medicinal compounds |
-
2001
- 2001-07-09 CN CN01812607A patent/CN1441784A/zh active Pending
- 2001-07-09 HU HU0301258A patent/HUP0301258A2/hu unknown
- 2001-07-09 MX MXPA03000337A patent/MXPA03000337A/es unknown
- 2001-07-09 IL IL15361101A patent/IL153611A0/xx unknown
- 2001-07-09 WO PCT/EP2001/007887 patent/WO2002004423A1/en not_active Application Discontinuation
- 2001-07-09 AU AU2001278476A patent/AU2001278476A1/en not_active Abandoned
- 2001-07-09 SK SK32-2003A patent/SK322003A3/sk not_active Application Discontinuation
- 2001-07-09 RU RU2003104017/04A patent/RU2003104017A/ru not_active Application Discontinuation
- 2001-07-09 NZ NZ523553A patent/NZ523553A/en unknown
- 2001-07-09 EP EP01956519A patent/EP1303491A1/en not_active Withdrawn
- 2001-07-09 JP JP2002509290A patent/JP2004502759A/ja not_active Withdrawn
- 2001-07-09 CA CA002413035A patent/CA2413035A1/en not_active Abandoned
- 2001-07-09 CZ CZ200392A patent/CZ200392A3/cs unknown
- 2001-07-09 KR KR10-2003-7000363A patent/KR20030022270A/ko not_active Application Discontinuation
- 2001-07-09 BR BR0112338-6A patent/BR0112338A/pt not_active IP Right Cessation
- 2001-07-09 US US10/332,792 patent/US6642253B2/en not_active Expired - Fee Related
- 2001-07-09 PL PL35978701A patent/PL359787A1/xx not_active Application Discontinuation
- 2001-07-10 PE PE2001000684A patent/PE20020209A1/es not_active Application Discontinuation
- 2001-07-11 AR ARP010103283A patent/AR029596A1/es not_active Application Discontinuation
-
2003
- 2003-01-03 ZA ZA200300080A patent/ZA200300080B/en unknown
- 2003-01-10 EC EC2003004422A patent/ECSP034422A/es unknown
- 2003-01-10 HR HR20030017A patent/HRP20030017A2/hr not_active Application Discontinuation
- 2003-01-10 NO NO20030145A patent/NO20030145L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0301258A2 (hu) | 2003-08-28 |
| AR029596A1 (es) | 2003-07-02 |
| IL153611A0 (en) | 2003-07-06 |
| AU2001278476A1 (en) | 2002-01-21 |
| PE20020209A1 (es) | 2002-03-19 |
| BR0112338A (pt) | 2003-07-22 |
| WO2002004423A1 (en) | 2002-01-17 |
| EP1303491A1 (en) | 2003-04-23 |
| US20030166579A1 (en) | 2003-09-04 |
| ZA200300080B (en) | 2004-04-05 |
| KR20030022270A (ko) | 2003-03-15 |
| NZ523553A (en) | 2004-04-30 |
| RU2003104017A (ru) | 2004-08-20 |
| PL359787A1 (en) | 2004-09-06 |
| WO2002004423A8 (en) | 2003-03-06 |
| WO2002004423A9 (en) | 2003-05-15 |
| MXPA03000337A (es) | 2004-04-05 |
| NO20030145D0 (no) | 2003-01-10 |
| JP2004502759A (ja) | 2004-01-29 |
| SK322003A3 (en) | 2003-06-03 |
| US6642253B2 (en) | 2003-11-04 |
| CN1441784A (zh) | 2003-09-10 |
| CA2413035A1 (en) | 2002-01-17 |
| ECSP034422A (es) | 2003-03-10 |
| CZ200392A3 (cs) | 2003-05-14 |
| NO20030145L (no) | 2003-01-10 |
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