ZA200209018B - Factor VIIa inhibitory (thio)urea derivatives, their preparation and their use. - Google Patents
Factor VIIa inhibitory (thio)urea derivatives, their preparation and their use. Download PDFInfo
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- ZA200209018B ZA200209018B ZA200209018A ZA200209018A ZA200209018B ZA 200209018 B ZA200209018 B ZA 200209018B ZA 200209018 A ZA200209018 A ZA 200209018A ZA 200209018 A ZA200209018 A ZA 200209018A ZA 200209018 B ZA200209018 B ZA 200209018B
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- South Africa
- Prior art keywords
- alkyl
- het
- aryl
- alkoxy
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- 230000002401 inhibitory effect Effects 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 title description 2
- 108010054265 Factor VIIa Proteins 0.000 title 1
- 229940012414 factor viia Drugs 0.000 title 1
- -1 hydroxycarbonyl- Chemical group 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 230000023555 blood coagulation Effects 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 208000001435 Thromboembolism Diseases 0.000 claims description 2
- 125000000656 azaniumyl group Chemical group [H][N+]([H])([H])[*] 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 6
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
- 125000001651 cyanato group Chemical group [*]OC#N 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- WRFHGDPIDHPWIQ-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-(ethoxymethyl)phenyl]-n-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O=C1N(CC=2C=C(COCC)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C(CCCC)=NC21CCCC2 WRFHGDPIDHPWIQ-UHFFFAOYSA-N 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 claims 1
- 230000028709 inflammatory response Effects 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
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- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
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- 150000003672 ureas Chemical class 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00112116A EP1162194A1 (de) | 2000-06-06 | 2000-06-06 | Auf Faktor VIIa inhibitorisch wirkende (Thio)-Harnstoff Verbindungen, Verfahren zu deren Herstellung und deren Verwendung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200209018B true ZA200209018B (en) | 2003-10-08 |
Family
ID=8168926
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200209018A ZA200209018B (en) | 2000-06-06 | 2002-11-06 | Factor VIIa inhibitory (thio)urea derivatives, their preparation and their use. |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US6743790B2 (de) |
| EP (2) | EP1162194A1 (de) |
| JP (1) | JP4809570B2 (de) |
| KR (1) | KR101011345B1 (de) |
| CN (1) | CN1208314C (de) |
| AR (1) | AR030936A1 (de) |
| AU (2) | AU2001277494B2 (de) |
| BR (1) | BR0111264A (de) |
| CA (1) | CA2410862C (de) |
| CZ (1) | CZ20023963A3 (de) |
| DE (1) | DE60139320D1 (de) |
| DK (1) | DK1299354T3 (de) |
| EE (1) | EE200200617A (de) |
| ES (1) | ES2330412T3 (de) |
| HK (1) | HK1055941A1 (de) |
| HR (1) | HRP20020961A2 (de) |
| HU (1) | HUP0301631A2 (de) |
| IL (2) | IL153220A0 (de) |
| MX (1) | MXPA02009789A (de) |
| MY (1) | MY129363A (de) |
| NO (1) | NO328546B1 (de) |
| NZ (1) | NZ522960A (de) |
| PL (1) | PL359584A1 (de) |
| PT (1) | PT1299354E (de) |
| RU (1) | RU2286337C2 (de) |
| SK (1) | SK17032002A3 (de) |
| TW (1) | TWI283662B (de) |
| WO (1) | WO2001094301A2 (de) |
| YU (1) | YU89202A (de) |
| ZA (1) | ZA200209018B (de) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4567439B2 (ja) * | 2002-04-27 | 2010-10-20 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | カルボン酸アミド |
| AU2003265398A1 (en) * | 2002-08-09 | 2004-02-25 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds and methods to modulate coagulation |
| JP2007505160A (ja) * | 2003-05-20 | 2007-03-08 | ジェネンテック・インコーポレーテッド | 第ＶＩＩａ因子のアシルスルファミド阻害剤 |
| EP1626966A1 (de) * | 2003-05-20 | 2006-02-22 | Genentech, Inc. | Benzofuran-hemmer des faktors viia |
| US7208601B2 (en) * | 2003-08-08 | 2007-04-24 | Mjalli Adnan M M | Aryl and heteroaryl compounds, compositions, and methods of use |
| AU2004263508A1 (en) * | 2003-08-08 | 2005-02-17 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions, and methods of use |
| WO2005014534A1 (en) * | 2003-08-08 | 2005-02-17 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions, and methods of use |
| JP4478157B2 (ja) * | 2004-10-13 | 2010-06-09 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ヒドラジド誘導体 |
| TW200630337A (en) * | 2004-10-14 | 2006-09-01 | Euro Celtique Sa | Piperidinyl compounds and the use thereof |
| WO2006089954A2 (en) * | 2005-02-24 | 2006-08-31 | Novo Nordisk Health Care Ag | Compounds for stabilizing factor vii polypeptide formulations |
| EP1856091A1 (de) * | 2005-02-24 | 2007-11-21 | Novo Nordisk Health Care AG | Verbindungen für formulierungen von polypeptiden mit dem stabilisierungsfaktor vii |
| US20090130085A1 (en) * | 2005-02-24 | 2009-05-21 | Novo Nordish Healthcare Ag | Amidino-Compounds for Stabilizing Factor VII Polypeptide Formulations |
| WO2006134173A2 (en) | 2005-06-17 | 2006-12-21 | Novo Nordisk Health Care Ag | Selective reduction and derivatization of engineered proteins comprising at least one non-native cysteine |
| RS52030B (en) | 2006-03-24 | 2012-04-30 | Eisai R&D Management Co., Ltd. | DERIVAT TRIAZOLONA |
| US8247442B2 (en) * | 2006-03-29 | 2012-08-21 | Purdue Pharma L.P. | Benzenesulfonamide compounds and their use |
| WO2007118853A1 (en) * | 2006-04-13 | 2007-10-25 | Euro-Celtique S.A. | Benzenesulfonamide compounds and their use as blockers of calcium channels |
| WO2007118854A1 (en) * | 2006-04-13 | 2007-10-25 | Euro-Celtique S.A. | Benzenesulfonamide compounds and the use thereof |
| US8399486B2 (en) * | 2007-04-09 | 2013-03-19 | Purdue Pharma L.P. | Benzenesulfonyl compounds and the use thereof |
| EP2202231A4 (de) * | 2007-09-21 | 2011-09-28 | Eisai R&D Man Co Ltd | 2,3-dihydroiminoisoindolderivate |
| WO2009040659A2 (en) * | 2007-09-28 | 2009-04-02 | Purdue Pharma L.P. | Benzenesulfonamide compounds and the use thereof |
| MX357737B (es) | 2011-10-26 | 2018-07-23 | Allergan Inc | Derivados de amida de aminoacidos sustituidos con n-urea como moduladores de receptor de tipo peptido receptor de formilo-1(fprl-1) . |
| CA2870356A1 (en) * | 2012-04-16 | 2013-10-24 | Allergan, Inc. | (2-ureidoacetamido)alkyl derivatives as formyl peptide receptor 2 modulators |
| WO2014057069A1 (en) | 2012-10-10 | 2014-04-17 | Novo Nordisk Health Care Ag | Liquid pharmaceutical composition of factor vii polypeptide |
| EP2964214A1 (de) | 2013-03-06 | 2016-01-13 | Allergan, Inc. | Verwendung von agonisten des formylpeptidrezeptors 2 zur behandlung von hautekrankungen |
| RU2768730C2 (ru) | 2013-03-06 | 2022-03-24 | Аллерган, Инк. | Применение агонистов формилпептидного рецептора 2 для лечения воспалительных заболеваний глаз |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5273982A (en) * | 1990-03-09 | 1993-12-28 | Hoffmann-La Roche Inc. | Acetic acid derivatives |
| US5506134A (en) | 1990-10-22 | 1996-04-09 | Corvas International, Inc. | Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex |
| WO1992013552A1 (en) * | 1991-02-05 | 1992-08-20 | Smithkline Beecham Corporation | Anti-aggregatory peptides containing an aromatic ester or amide |
| US5788965A (en) | 1991-02-28 | 1998-08-04 | Novo Nordisk A/S | Modified factor VII |
| US5833982A (en) | 1991-02-28 | 1998-11-10 | Zymogenetics, Inc. | Modified factor VII |
| JP3387948B2 (ja) * | 1992-12-04 | 2003-03-17 | 富山化学工業株式会社 | 新規なフェニルアラニン誘導体またはその塩 |
| US5314902A (en) * | 1993-01-27 | 1994-05-24 | Monsanto Company | Urea derivatives useful as platelet aggregation inhibitors |
| DE4309867A1 (de) * | 1993-03-26 | 1994-09-29 | Cassella Ag | Neue Harnstoffderivate, ihre Herstellung und Verwendung |
| GB9313268D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Chemical compounds |
| GB9313269D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Allophanic acid derivatives |
| WO1995008550A1 (en) * | 1993-09-24 | 1995-03-30 | Abbott Laboratories | Endothelin antagonists |
| AU7862794A (en) * | 1993-10-19 | 1995-05-08 | Sumitomo Pharmaceuticals Company, Limited | 2,3-diaminopropionic acid derivative |
| US5674894A (en) * | 1995-05-15 | 1997-10-07 | G.D. Searle & Co. | Amidine derivatives useful as platelet aggregation inhibitors and vasodilators |
| EP0880320A4 (de) * | 1996-01-30 | 1999-06-16 | Merck & Co Inc | Inhibitoren der farnesyl-protein transferase |
| CN100418951C (zh) * | 1997-11-18 | 2008-09-17 | 帝人医药株式会社 | 环胺衍生物及其作为药物的用途 |
| EP0987274A1 (de) * | 1998-09-15 | 2000-03-22 | Hoechst Marion Roussel Deutschland GmbH | Faktor VIIa Inhibitore |
-
2000
- 2000-06-06 EP EP00112116A patent/EP1162194A1/de not_active Withdrawn
-
2001
- 2001-05-26 BR BR0111264-3A patent/BR0111264A/pt not_active IP Right Cessation
- 2001-05-26 EP EP01955291A patent/EP1299354B1/de not_active Expired - Lifetime
- 2001-05-26 KR KR1020027016691A patent/KR101011345B1/ko not_active IP Right Cessation
- 2001-05-26 YU YU89202A patent/YU89202A/sh unknown
- 2001-05-26 CZ CZ20023963A patent/CZ20023963A3/cs unknown
- 2001-05-26 ES ES01955291T patent/ES2330412T3/es not_active Expired - Lifetime
- 2001-05-26 NZ NZ522960A patent/NZ522960A/en unknown
- 2001-05-26 HU HU0301631A patent/HUP0301631A2/hu unknown
- 2001-05-26 SK SK1703-2002A patent/SK17032002A3/sk not_active Application Discontinuation
- 2001-05-26 DK DK01955291T patent/DK1299354T3/da active
- 2001-05-26 MX MXPA02009789A patent/MXPA02009789A/es active IP Right Grant
- 2001-05-26 EE EEP200200617A patent/EE200200617A/xx unknown
- 2001-05-26 DE DE60139320T patent/DE60139320D1/de not_active Expired - Lifetime
- 2001-05-26 RU RU2002135308/04A patent/RU2286337C2/ru not_active IP Right Cessation
- 2001-05-26 JP JP2002501818A patent/JP4809570B2/ja not_active Expired - Fee Related
- 2001-05-26 CN CNB018088309A patent/CN1208314C/zh not_active Expired - Fee Related
- 2001-05-26 AU AU2001277494A patent/AU2001277494B2/en not_active Ceased
- 2001-05-26 CA CA002410862A patent/CA2410862C/en not_active Expired - Fee Related
- 2001-05-26 IL IL15322001A patent/IL153220A0/xx unknown
- 2001-05-26 AU AU7749401A patent/AU7749401A/xx active Pending
- 2001-05-26 WO PCT/EP2001/006029 patent/WO2001094301A2/en active IP Right Grant
- 2001-05-26 PL PL01359584A patent/PL359584A1/xx not_active Application Discontinuation
- 2001-05-26 PT PT01955291T patent/PT1299354E/pt unknown
- 2001-06-04 TW TW090113412A patent/TWI283662B/zh not_active IP Right Cessation
- 2001-06-04 AR ARP010102657A patent/AR030936A1/es active IP Right Grant
- 2001-06-05 MY MYPI20012631A patent/MY129363A/en unknown
- 2001-06-06 US US09/874,318 patent/US6743790B2/en not_active Expired - Lifetime
-
2002
- 2002-11-06 ZA ZA200209018A patent/ZA200209018B/en unknown
- 2002-12-02 IL IL153220A patent/IL153220A/en not_active IP Right Cessation
- 2002-12-03 NO NO20025810A patent/NO328546B1/no not_active IP Right Cessation
- 2002-12-05 HR HRP20020961 patent/HRP20020961A2/hr not_active Application Discontinuation
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2003
- 2003-11-12 HK HK03108194A patent/HK1055941A1/xx not_active IP Right Cessation
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