JP3171850B2 - アミジノ誘導体およびその一酸化窒素シンターゼ阻害剤としての使用 - Google Patents
アミジノ誘導体およびその一酸化窒素シンターゼ阻害剤としての使用Info
- Publication number
- JP3171850B2 JP3171850B2 JP51127393A JP51127393A JP3171850B2 JP 3171850 B2 JP3171850 B2 JP 3171850B2 JP 51127393 A JP51127393 A JP 51127393A JP 51127393 A JP51127393 A JP 51127393A JP 3171850 B2 JP3171850 B2 JP 3171850B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- formula
- group
- pharmaceutically acceptable
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/14—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Hydrogenated Pyridines (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Cephalosporin Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919127376A GB9127376D0 (en) | 1991-12-24 | 1991-12-24 | Amidino derivatives |
| GB9127376.3 | 1991-12-24 | ||
| PCT/GB1992/002387 WO1993013055A1 (en) | 1991-12-24 | 1992-12-23 | Amidino derivatives and their use as nitric oxide synthase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH07502512A JPH07502512A (ja) | 1995-03-16 |
| JP3171850B2 true JP3171850B2 (ja) | 2001-06-04 |
Family
ID=10706815
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51127393A Expired - Fee Related JP3171850B2 (ja) | 1991-12-24 | 1992-12-23 | アミジノ誘導体およびその一酸化窒素シンターゼ阻害剤としての使用 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5863931A (show.php) |
| EP (1) | EP0618898B1 (show.php) |
| JP (1) | JP3171850B2 (show.php) |
| AT (1) | ATE178588T1 (show.php) |
| AU (1) | AU669345B2 (show.php) |
| CA (1) | CA2126327C (show.php) |
| CY (1) | CY2197B1 (show.php) |
| DE (1) | DE69228879T2 (show.php) |
| DK (1) | DK0618898T3 (show.php) |
| ES (1) | ES2130247T3 (show.php) |
| GB (1) | GB9127376D0 (show.php) |
| GR (1) | GR3030492T3 (show.php) |
| HU (1) | HU217618B (show.php) |
| IL (1) | IL104212A (show.php) |
| MY (1) | MY109421A (show.php) |
| NZ (1) | NZ246202A (show.php) |
| RU (1) | RU2130014C1 (show.php) |
| TW (1) | TW255881B (show.php) |
| WO (1) | WO1993013055A1 (show.php) |
| ZA (1) | ZA9210018B (show.php) |
Families Citing this family (121)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9312761D0 (en) * | 1993-06-21 | 1993-08-04 | Wellcome Found | Amino acid derivatives |
| US5424447A (en) * | 1993-07-07 | 1995-06-13 | The Medical College Of Wisconsin Research Foundation, Inc. | Heme binding compounds and use thereof |
| HUT75876A (en) * | 1993-08-12 | 1997-05-28 | Astra Ab | Amidine derivatives with nitric oxide synthetase activities, pharmaceutical compositions containing them and process for their preparation |
| CN1071746C (zh) * | 1993-08-12 | 2001-09-26 | 阿斯特拉公司 | 具有氧化氮合成酶活性的脒衍生物 |
| US6297276B1 (en) | 1993-10-04 | 2001-10-02 | Glaxosmithkline | Substituted urea and isothiourea derivatives as no synthase inhibitors |
| US6225305B1 (en) | 1993-10-04 | 2001-05-01 | Glaxo Wellcome Inc. | Substituted urea and isothiorea derivatives as no synthase inhibitors |
| DK0724435T3 (da) * | 1993-10-21 | 2002-11-25 | Searle & Co | Amidinoderivater, der er nyttige som nitrogenoxid-synthase-inhibitorer |
| KR100342275B1 (ko) * | 1993-10-21 | 2002-12-05 | 지.디. 썰 엘엘씨 | 산화질소신타제저해제로서유용한아미디노유도체 |
| DE4337906A1 (de) * | 1993-11-08 | 1995-05-11 | Cassella Ag | Verwendung von Cumarinderivaten |
| AU1209995A (en) * | 1993-11-17 | 1995-06-06 | Duke University Medical Center | Use of nitric oxide synthase inhibitors in the treatment of autoimmune diseases |
| GB9326136D0 (en) * | 1993-12-22 | 1994-02-23 | Erba Carlo Spa | Biologically active 3-substituted oxindole derivatives useful as anti-angiogenic agents |
| GB9404400D0 (en) * | 1994-03-07 | 1994-04-20 | Wood Pauline J | Potentiation of bioreductive agents |
| ES2151055T3 (es) * | 1994-03-10 | 2000-12-16 | Searle & Co | Derivados de l-n6-(1-iminoetil)lisina utiles como inhibidores de oxido nitrico sintasa. |
| WO1995025717A1 (en) * | 1994-03-24 | 1995-09-28 | G.D. Searle & Co. | Amidino derivatives useful as nitric oxide synthase inhibitors |
| MX9605366A (es) * | 1994-05-07 | 1997-12-31 | Astra Ab | Derivados de amidina biciclicos como inhibidores de la oxido nitrico sintetasa. |
| CA2192668A1 (en) | 1994-06-15 | 1995-12-21 | Harold Francis Hodson | Amidino sulfone derivatives for use as inos inhibitors claims |
| AU723677B2 (en) * | 1994-09-22 | 2000-08-31 | William Harvey Research Limited | Pharmaceutical control of inflammation |
| US6066333A (en) * | 1994-09-22 | 2000-05-23 | William Harvey Research Limited | Pharmaceutical control of inflammation |
| CA2132690A1 (en) * | 1994-09-22 | 1996-03-23 | Dean Willis | Control and modulation of inflammatory response in humans in need of such control and modulation |
| US5684008A (en) | 1994-11-09 | 1997-11-04 | G. D. Searle & Co. | Aminotetrazole derivatives useful as nitric oxide synthase inhibitors |
| FR2727111B1 (fr) * | 1994-11-21 | 1997-01-17 | Hoechst Lab | Nouveaux analogues soufres d'aminoacides, leur procede de preparation et leurs applications comme medicaments |
| JPH08333258A (ja) | 1994-12-14 | 1996-12-17 | Japan Tobacco Inc | チアジン又はチアゼピン誘導体及びそれら化合物を含有してなる一酸化窒素合成酵素阻害剤 |
| GB9425701D0 (en) * | 1994-12-20 | 1995-02-22 | Wellcome Found | Enzyme inhibitors |
| WO1996021445A1 (en) * | 1995-01-13 | 1996-07-18 | The General Hospital Corporation | Methods of inhibiting neurodegenerative diseases |
| ATE246678T1 (de) * | 1995-04-20 | 2003-08-15 | Searle & Co | Zyclische amidino mittel als stickstoffoxid- synthase inhibitoren |
| US5830917A (en) * | 1995-09-11 | 1998-11-03 | G. D. Searle & Co. | L-N6 -(1-iminoethyl) lysine derivatives useful as nitric oxide synthase inhibitors |
| US5908842A (en) * | 1995-12-08 | 1999-06-01 | Merck & Co., Inc. | Substituted 2-acylamino-pyridines as inhibitors of nitric oxide synthase |
| US5981511A (en) * | 1996-03-06 | 1999-11-09 | G.D. Searle & Co. | Hydroxyamidino derivatives useful as nitric oxide synthase inhibitors |
| US5945408A (en) * | 1996-03-06 | 1999-08-31 | G.D. Searle & Co. | Hydroxyanidino derivatives useful as nitric oxide synthase inhibitors |
| US6566330B1 (en) * | 1996-10-22 | 2003-05-20 | Medical University Of South Carolina Foundation Research Development | Positively charged non-natural amino acids, methods of making and using thereof in peptides |
| US6043218A (en) * | 1996-10-22 | 2000-03-28 | Medical University Of South Carolina | Positively charged non-natural amino acids, methods of making thereof, and use thereof in peptides |
| US6160000A (en) * | 1996-12-23 | 2000-12-12 | Merck & Co., Inc. | Antidiabetic agents based on aryl and heteroarylacetic acids |
| US6090839A (en) * | 1996-12-23 | 2000-07-18 | Merck & Co., Inc. | Antidiabetic agents |
| US6620848B2 (en) | 1997-01-13 | 2003-09-16 | Smithkline Beecham Corporation | Nitric oxide synthase inhibitors |
| MY117948A (en) * | 1997-01-13 | 2004-08-30 | Glaxo Group Ltd | Nitride oxide synthase inhibitors. |
| US6369272B1 (en) | 1997-01-13 | 2002-04-09 | Glaxosmithkline | Nitric oxide synthase inhibitors |
| FR2764889B1 (fr) * | 1997-06-20 | 2000-09-01 | Sod Conseils Rech Applic | Nouveaux derives du 2-(iminomethyl)amino-phenyle, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
| ATE499343T1 (de) * | 1997-07-03 | 2011-03-15 | Us Gov Health & Human Serv | Stickoxid freistetzende amidin- und enaminverwandte diazeniumdiolate, zubereitungen und verwendungen davon und verfahren zu ihrer herstellung |
| US5981556A (en) * | 1997-07-22 | 1999-11-09 | G.D. Searle & Co. | 1,3-diazolino and 1,3-diazolidino heterocycles as useful nitric oxide synthase inhibitors |
| CN1171861C (zh) * | 1998-03-11 | 2004-10-20 | G·D·西尔公司 | 用作一氧化氮合酶抑制剂的卤代脒基氨基酸衍生物 |
| EP1067926A2 (en) * | 1998-04-06 | 2001-01-17 | Fujisawa Pharmaceutical Co., Ltd. | Immunosuppressive imidazole derivatives and their combination preparations with tacrolimus or cyclosporins |
| GB9811599D0 (en) * | 1998-05-30 | 1998-07-29 | Glaxo Group Ltd | Nitric oxide synthase inhibitors |
| US6552052B2 (en) | 1998-06-10 | 2003-04-22 | Monsanto/G.D. Searle | Pyrrolo[2,1-c][1,2,4] thiadiazoles and Pyrollo[2,1-c][1,12,4]oxadiazoles useful as nitric oxide synthase inhibitors |
| AU4821799A (en) | 1998-06-10 | 1999-12-30 | G.D. Searle & Co. | Heterobicyclic and tricyclic nitric oxide synthase inhibitors |
| EP1112068A2 (en) | 1998-09-08 | 2001-07-04 | Monsanto Company | Methods of treating osteoarthritis with inducible nitric oxide synthase inhibitors |
| AU2847200A (en) * | 1999-01-27 | 2000-08-18 | G.D. Searle & Co. | Novel hydroxyamidino carboxylate derivatives useful as nitric oxide synthase inhibitors |
| NZ520813A (en) | 2000-03-24 | 2004-05-28 | Pharmacia Corp | Amidino compounds useful as nitric oxide synthase inhibitors |
| AR034120A1 (es) * | 2000-04-13 | 2004-02-04 | Pharmacia Corp | Compuesto derivado halogenado del acido 2-amino-4,5 heptenoico, composicion farmaceutica que lo comprende y el uso de dicho compuesto y dicha composicion en la fabricacion de un medicamento para inhibir o modular la sintesis de acido nitrico |
| AR032318A1 (es) | 2000-04-13 | 2003-11-05 | Pharmacia Corp | Compuesto derivado halogenado del acido 2-amino-5,6 heptenoico; composicion farmaceutica que lo comprende y su uso en la fabricacion de un medicamento util como inhibidor de la oxido nitrico sintetasa |
| US6787668B2 (en) | 2000-04-13 | 2004-09-07 | Pharmacia Corporation | 2-amino-4,5 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| US6956131B2 (en) | 2000-04-13 | 2005-10-18 | Pharmacia Corporation | 2-amino-3, 4 heptenoic compounds useful as nitric oxide synthase inhibitors |
| AR030416A1 (es) | 2000-04-13 | 2003-08-20 | Pharmacia Corp | COMPUESTO DERIVADO HALOGENADO DEL ACIDO 2-AMINO-3,4 HEPTENOICO, COMPOSICION FARMACEUTICA QUE LO COMPRENDE Y SU USO EN LA FABRICACION DE UN MEDICAMENTO uTIL COMO INHIBIDOR DE LA OXIDO NITRICO SINTETASA |
| US6545170B2 (en) | 2000-04-13 | 2003-04-08 | Pharmacia Corporation | 2-amino-5, 6 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| US6344473B1 (en) | 2000-08-07 | 2002-02-05 | G.D. Searle & Co. | Imidazoles useful as nitric oxide synthase inhibitors |
| AR031608A1 (es) * | 2000-09-15 | 2003-09-24 | Pharmacia Corp | Derivados de los acidos 2-amino-2-alquil-3-hexenoico y -hexinoico utiles como inhibidores de oxido nitrico sintetasa |
| AR031129A1 (es) | 2000-09-15 | 2003-09-10 | Pharmacia Corp | Derivados de los acidos 2-amino-2-alquil-4-hexenoico y -hexinoico utiles como inhibidores de oxido nitrico sintetasa |
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| ITTO20010110A1 (it) | 2001-02-08 | 2002-08-08 | Rotta Research Lab | Nuovi derivati benzamidinici dotati di attivita' anti-infiammatoria ed immunosoppressiva. |
| US7012098B2 (en) | 2001-03-23 | 2006-03-14 | Pharmacia Corporation | Inhibitors of inducible nitric oxide synthase for chemoprevention and treatment of cancers |
| US6673338B1 (en) | 2001-09-10 | 2004-01-06 | The United States Of America As Represented By The Department Of Health And Human Services | Nitric oxide-releasing imidate and thioimidate diazeniumdiolates, compositions, uses thereof and method of making same |
| US20030109522A1 (en) * | 2001-09-24 | 2003-06-12 | Manning Pamela T. | Ophthalmologic treatment methods using selective iNOS inhibitors |
| US6949530B2 (en) | 2002-07-18 | 2005-09-27 | The United States Of America As Represented By The Department Of Health And Human Services | Nitric oxide-releasing amidine diazeniumdiolates, compositions and uses thereof and method of making same |
| BR0313204A (pt) * | 2002-08-02 | 2005-06-28 | Pharmacia Corp | Métodos para tratamento e prevenção de condições gastrointestinais |
| PL375557A1 (en) * | 2002-08-23 | 2005-11-28 | Pharmacia Corporation | Crystalline solid form of (2s-5z)-2-amino-7-(ethanimidoylamino)-2-methylhept-5-enoic acid |
| TWI328009B (en) | 2003-05-21 | 2010-08-01 | Glaxo Group Ltd | Quinoline derivatives as phosphodiesterase inhibitors |
| GB0316290D0 (en) | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Novel compounds |
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| FI832053L (fi) * | 1982-06-10 | 1983-12-11 | Syntex Inc | Nonapeptid- och dekapeptidanaloger av lhrh anvaendbara som lhrh-antagonister samt deras framstaellningsfoerfarande |
| US5028627A (en) * | 1989-09-13 | 1991-07-02 | Cornell Research Foundation, Inc. | Method of using arginine derivatives to inhibit systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor |
| GB8929076D0 (en) * | 1989-12-22 | 1990-02-28 | Scras | Treatment of shock by blocking agents of edrf effect or formation |
| AU636713B2 (en) * | 1990-02-26 | 1993-05-06 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of nitric oxide biosynthesis |
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1991
- 1991-12-24 GB GB919127376A patent/GB9127376D0/en active Pending
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1992
- 1992-12-23 DK DK93900357T patent/DK0618898T3/da active
- 1992-12-23 EP EP93900357A patent/EP0618898B1/en not_active Expired - Lifetime
- 1992-12-23 WO PCT/GB1992/002387 patent/WO1993013055A1/en not_active Ceased
- 1992-12-23 TW TW081110312A patent/TW255881B/zh active
- 1992-12-23 NZ NZ246202A patent/NZ246202A/xx not_active IP Right Cessation
- 1992-12-23 ZA ZA9210018A patent/ZA9210018B/xx unknown
- 1992-12-23 AT AT93900357T patent/ATE178588T1/de active
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- 1992-12-23 US US08/256,032 patent/US5863931A/en not_active Expired - Lifetime
- 1992-12-23 RU RU94031155A patent/RU2130014C1/ru not_active IP Right Cessation
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- 1992-12-23 AU AU31692/93A patent/AU669345B2/en not_active Ceased
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1999
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2000
- 2000-10-05 CY CY0000048A patent/CY2197B1/xx unknown
Non-Patent Citations (1)
| Title |
|---|
| Ｂｒ．Ｊ．Ｐｈａｒｍａｃｏｌ．，Ｖｏｌ．１０１，Ｎｏ．３（１９９０）ｐ．７４６−ｐ．７５２ |
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| AU3169293A (en) | 1993-07-28 |
| GB9127376D0 (en) | 1992-02-19 |
| HU217618B (hu) | 2000-03-28 |
| NZ246202A (en) | 1996-05-28 |
| EP0618898B1 (en) | 1999-04-07 |
| JPH07502512A (ja) | 1995-03-16 |
| ATE178588T1 (de) | 1999-04-15 |
| CA2126327A1 (en) | 1993-07-08 |
| CA2126327C (en) | 2005-05-17 |
| ZA9210018B (en) | 1994-06-23 |
| CY2197B1 (en) | 2002-11-08 |
| DK0618898T3 (da) | 1999-10-18 |
| RU94031155A (ru) | 1996-04-20 |
| MY109421A (en) | 1997-01-31 |
| RU2130014C1 (ru) | 1999-05-10 |
| IL104212A (en) | 1998-02-22 |
| IL104212A0 (en) | 1993-05-13 |
| GR3030492T3 (en) | 1999-10-29 |
| AU669345B2 (en) | 1996-06-06 |
| EP0618898A1 (en) | 1994-10-12 |
| DE69228879D1 (de) | 1999-05-12 |
| ES2130247T3 (es) | 1999-07-01 |
| HUT70502A (en) | 1995-10-30 |
| WO1993013055A1 (en) | 1993-07-08 |
| DE69228879T2 (de) | 1999-08-26 |
| TW255881B (show.php) | 1995-09-01 |
| HU9401848D0 (en) | 1994-09-28 |
| US5863931A (en) | 1999-01-26 |
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