NO311643B1 - <alfa>-substituerte arylsulfonamidohydroksamsyrer som TNF- <alfa>-og matrisemetalloproteinase-inhibitorer, farmasöytiskpreparat inneholdende slike forbindelser, deres anvendelse, ogfremgangsmåte for deres fremstilling - Google Patents
<alfa>-substituerte arylsulfonamidohydroksamsyrer som TNF- <alfa>-og matrisemetalloproteinase-inhibitorer, farmasöytiskpreparat inneholdende slike forbindelser, deres anvendelse, ogfremgangsmåte for deres fremstilling Download PDFInfo
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- NO311643B1 NO311643B1 NO19982579A NO982579A NO311643B1 NO 311643 B1 NO311643 B1 NO 311643B1 NO 19982579 A NO19982579 A NO 19982579A NO 982579 A NO982579 A NO 982579A NO 311643 B1 NO311643 B1 NO 311643B1
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Classifications
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
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- A—HUMAN NECESSITIES
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- 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
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- 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
- C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US866195P | 1995-12-15 | 1995-12-15 | |
| PCT/EP1996/005362 WO1997022587A1 (en) | 1995-12-15 | 1996-12-03 | Alpha-substituted arylsulphonamido hydroxamic acids as tnf-alpha and matrix metalloproteinase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO982579D0 NO982579D0 (no) | 1998-06-05 |
| NO982579L NO982579L (no) | 1998-06-05 |
| NO311643B1 true NO311643B1 (no) | 2001-12-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19982579A NO311643B1 (no) | 1995-12-15 | 1998-06-05 | <alfa>-substituerte arylsulfonamidohydroksamsyrer som TNF- <alfa>-og matrisemetalloproteinase-inhibitorer, farmasöytiskpreparat inneholdende slike forbindelser, deres anvendelse, ogfremgangsmåte for deres fremstilling |
Country Status (26)
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| US (1) | US5770624A (enExample) |
| EP (1) | EP0873312B1 (enExample) |
| JP (1) | JP4112004B2 (enExample) |
| KR (1) | KR100452941B1 (enExample) |
| CN (1) | CN1173948C (enExample) |
| AR (1) | AR005068A1 (enExample) |
| AT (1) | ATE219058T1 (enExample) |
| AU (1) | AU709489B2 (enExample) |
| BR (1) | BR9612136B1 (enExample) |
| CZ (1) | CZ292431B6 (enExample) |
| DE (1) | DE69621830T2 (enExample) |
| DK (1) | DK0873312T3 (enExample) |
| EA (1) | EA002019B1 (enExample) |
| ES (1) | ES2178724T3 (enExample) |
| HU (1) | HU226123B1 (enExample) |
| IL (1) | IL124524A (enExample) |
| MX (1) | MX9804793A (enExample) |
| NO (1) | NO311643B1 (enExample) |
| NZ (1) | NZ324287A (enExample) |
| PL (1) | PL187136B1 (enExample) |
| PT (1) | PT873312E (enExample) |
| SK (1) | SK78998A3 (enExample) |
| TR (1) | TR199801105T2 (enExample) |
| TW (1) | TW453995B (enExample) |
| WO (1) | WO1997022587A1 (enExample) |
| ZA (1) | ZA9610532B (enExample) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6500948B1 (en) | 1995-12-08 | 2002-12-31 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors-compositions, uses preparation and intermediates thereof |
| EA003294B1 (ru) * | 1995-12-08 | 2003-04-24 | Агурон Фармасьютикалс, Инк. | Ингибиторы металлопротеиназы, фармацевтические композиции, их содержащие, и их фармацевтические применения |
| US5962481A (en) | 1996-10-16 | 1999-10-05 | American Cyanamid Company | Preparation and use of ortho-sulfonamido heteroaryl hydroxamic acids as matrix metalloproteinase and tace inhibitors |
| US6548524B2 (en) | 1996-10-16 | 2003-04-15 | American Cyanamid Company | Preparation and use of ortho-sulfonamido bicyclic heteroaryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors |
| US5977408A (en) * | 1996-10-16 | 1999-11-02 | American Cyanamid Company | Preparation and use of β-sulfonamido hydroxamic acids as matrix metalloproteinase and TACE inhibitors |
| US5929097A (en) * | 1996-10-16 | 1999-07-27 | American Cyanamid Company | Preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix metalloproteinase and tace inhibitors |
| US6228869B1 (en) | 1996-10-16 | 2001-05-08 | American Cyanamid Company | Ortho-sulfonamido bicyclic hydroxamic acids as matrix metalloproteinase and TACE inhibitors |
| US6174915B1 (en) | 1997-03-25 | 2001-01-16 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses |
| US6008243A (en) * | 1996-10-24 | 1999-12-28 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use |
| US5985900A (en) * | 1997-04-01 | 1999-11-16 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses |
| IL127496A0 (en) * | 1997-12-19 | 1999-10-28 | Pfizer Prod Inc | The use of MMP inhibitors for the treatment of ocular angiogenesis |
| US6492394B1 (en) | 1998-12-22 | 2002-12-10 | Syntex (U.S.A.) Llc | Sulfonamide hydroxamates |
| US20040122011A1 (en) * | 1998-12-23 | 2004-06-24 | Pharmacia Corporation | Method of using a COX-2 inhibitor and a TACE inhibitors as a combination therapy |
| US6753337B2 (en) * | 1999-01-27 | 2004-06-22 | Wyeth Holdings Corporation | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors |
| US6762178B2 (en) | 1999-01-27 | 2004-07-13 | Wyeth Holdings Corporation | Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors |
| US6340691B1 (en) | 1999-01-27 | 2002-01-22 | American Cyanamid Company | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors |
| US6277885B1 (en) | 1999-01-27 | 2001-08-21 | American Cyanamid Company | Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors |
| US6225311B1 (en) | 1999-01-27 | 2001-05-01 | American Cyanamid Company | Acetylenic α-amino acid-based sulfonamide hydroxamic acid tace inhibitors |
| US6946473B2 (en) | 1999-01-27 | 2005-09-20 | Wyeth Holdings Corporation | Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors |
| BR0007784A (pt) | 1999-01-27 | 2002-02-05 | American Cyanamid Co | Composto, método para inibir mudanças patológicas mediadas pela enzima que converte o tnf-alfa (tace) em um mamìfero, composição farmacêutica, e, processo para preparar um composto |
| US6326516B1 (en) | 1999-01-27 | 2001-12-04 | American Cyanamid Company | Acetylenic β-sulfonamido and phosphinic acid amide hydroxamic acid TACE inhibitors |
| US6200996B1 (en) | 1999-01-27 | 2001-03-13 | American Cyanamid Company | Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors |
| US6313123B1 (en) | 1999-01-27 | 2001-11-06 | American Cyanamid Company | Acetylenic sulfonamide thiol tace inhibitors |
| GB9918684D0 (en) * | 1999-08-09 | 1999-10-13 | Novartis Ag | Organic compounds |
| GB9922825D0 (en) * | 1999-09-25 | 1999-11-24 | Smithkline Beecham Biolog | Medical use |
| AU2001237939A1 (en) * | 2000-02-08 | 2001-08-20 | Gulgun Tezel | Methods for treating glaucoma |
| US6531128B1 (en) * | 2000-02-08 | 2003-03-11 | Pharmacia Corporation | Methods for treating glaucoma |
| US6465508B1 (en) | 2000-02-25 | 2002-10-15 | Wyeth | Preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix metalloproteinase inhibitors |
| KR20030005230A (ko) * | 2000-03-21 | 2003-01-17 | 더 프록터 앤드 갬블 캄파니 | Ｎ-치환된 메탈로프로테아제 저해제를 함유하는 탄소환식측쇄 |
| CA2401728A1 (en) | 2000-03-21 | 2001-09-27 | The Procter & Gamble Company | Difluorobutyric acid metalloprotease inhibitors |
| WO2001070682A2 (en) * | 2000-03-21 | 2001-09-27 | The Procter & Gamble Company | Carbocyclic side chain containing metalloprotease inhibitors |
| RU2245876C2 (ru) | 2000-03-21 | 2005-02-10 | Дзе Проктер Энд Гэмбл Компани | Производные сульфонамидов и фармацевтическая композиция на их основе |
| JP2005507937A (ja) | 2001-11-01 | 2005-03-24 | ワイス・ホールディングズ・コーポレイション | マトリックスメタロプロテイナーゼおよびｔａｃｅ阻害剤としてのアレンアリールスルホンアミドヒドロキサム酸 |
| PE20030701A1 (es) | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| GB0208176D0 (en) * | 2002-04-09 | 2002-05-22 | Novartis Ag | Organic compounds |
| AU2003253346A1 (en) * | 2002-07-29 | 2004-02-23 | Novartis Ag | Use or arylsulfonamido-substituted hydroxamid acid matrix metalloproteinase inhibitors for the treatment or prevention of toxemia |
| AU2003294917A1 (en) * | 2002-12-20 | 2004-07-14 | Novartis Ag | Device and method for delivering mmp inhibitors |
| US7199155B2 (en) | 2002-12-23 | 2007-04-03 | Wyeth Holdings Corporation | Acetylenic aryl sulfonate hydroxamic acid TACE and matrix metalloproteinase inhibitors |
| EP1592458A1 (en) | 2003-02-10 | 2005-11-09 | GE Healthcare Limited | Diagnostic imaging agents with mmp inhibitory activity |
| EP1622617A2 (en) * | 2003-02-11 | 2006-02-08 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions based on anticholinergics and tace-inhibitors |
| DK2041181T3 (da) * | 2006-06-08 | 2011-08-29 | Helmholtz Zentrum Muenchen | Specifikke proteaseinhibitorer og deres anvendelse i cancerterapi |
| FR2947270B1 (fr) | 2009-06-30 | 2011-08-26 | Galderma Res & Dev | Nouveaux composes benzene-sulfonamides, leur procede de synthese et leur utilisation en medecine ainsi qu'en cosmetique |
| FR2947268B1 (fr) | 2009-06-30 | 2011-08-26 | Galderma Res & Dev | Nouveaux composes benzene-sulfonamides, leur procede de synthese et leur utilisation en medecine ainsi qu'en cosmetique |
| US20140275108A1 (en) | 2013-03-15 | 2014-09-18 | Galderma Research & Development | Novel benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine as well as in cosmetics |
| GB201510758D0 (en) | 2015-06-18 | 2015-08-05 | Ucb Biopharma Sprl | Novel TNFa structure for use in therapy |
| EP3199534B1 (en) | 2016-02-01 | 2018-09-05 | Galderma Research & Development | Benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine and cosmetics |
| GB201621907D0 (en) | 2016-12-21 | 2017-02-01 | Ucb Biopharma Sprl And Sanofi | Antibody epitope |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5552419A (en) * | 1993-01-06 | 1996-09-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5506242A (en) * | 1993-01-06 | 1996-04-09 | Ciba-Geigy Corporation | Arylsufonamido-substituted hydroxamic acids |
| US5455258A (en) * | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5646167A (en) * | 1993-01-06 | 1997-07-08 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamix acids |
| AU690703B2 (en) * | 1994-06-22 | 1998-04-30 | British Biotech Pharmaceuticals Limited | Metalloproteinase inhibitors |
| US5863949A (en) * | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
-
1996
- 1996-11-26 TW TW085114549A patent/TW453995B/zh not_active IP Right Cessation
- 1996-12-03 DK DK96942307T patent/DK0873312T3/da active
- 1996-12-03 BR BRPI9612136-0A patent/BR9612136B1/pt not_active IP Right Cessation
- 1996-12-03 KR KR10-1998-0704349A patent/KR100452941B1/ko not_active Expired - Fee Related
- 1996-12-03 NZ NZ324287A patent/NZ324287A/en unknown
- 1996-12-03 ES ES96942307T patent/ES2178724T3/es not_active Expired - Lifetime
- 1996-12-03 IL IL12452496A patent/IL124524A/en not_active IP Right Cessation
- 1996-12-03 DE DE69621830T patent/DE69621830T2/de not_active Expired - Lifetime
- 1996-12-03 CN CNB961990171A patent/CN1173948C/zh not_active Expired - Fee Related
- 1996-12-03 CZ CZ19981854A patent/CZ292431B6/cs not_active IP Right Cessation
- 1996-12-03 WO PCT/EP1996/005362 patent/WO1997022587A1/en not_active Ceased
- 1996-12-03 PT PT96942307T patent/PT873312E/pt unknown
- 1996-12-03 PL PL96327450A patent/PL187136B1/pl not_active IP Right Cessation
- 1996-12-03 AT AT96942307T patent/ATE219058T1/de not_active IP Right Cessation
- 1996-12-03 SK SK789-98A patent/SK78998A3/sk unknown
- 1996-12-03 AU AU11406/97A patent/AU709489B2/en not_active Ceased
- 1996-12-03 TR TR1998/01105T patent/TR199801105T2/xx unknown
- 1996-12-03 HU HU0000214A patent/HU226123B1/hu not_active IP Right Cessation
- 1996-12-03 EP EP96942307A patent/EP0873312B1/en not_active Expired - Lifetime
- 1996-12-03 EA EA199800529A patent/EA002019B1/ru not_active IP Right Cessation
- 1996-12-03 JP JP52245797A patent/JP4112004B2/ja not_active Expired - Fee Related
- 1996-12-10 US US08/763,273 patent/US5770624A/en not_active Expired - Lifetime
- 1996-12-13 ZA ZA9610532A patent/ZA9610532B/xx unknown
- 1996-12-13 AR ARP960105665A patent/AR005068A1/es unknown
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1998
- 1998-06-05 NO NO19982579A patent/NO311643B1/no unknown
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