NO324211B1 - Nye benzazepinderivater, farmasoytisk middel inneholdende forbindelsene samt deres anvendelse ved fremstilling av medikamenter - Google Patents
Nye benzazepinderivater, farmasoytisk middel inneholdende forbindelsene samt deres anvendelse ved fremstilling av medikamenter Download PDFInfo
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- NO324211B1 NO324211B1 NO19984852A NO984852A NO324211B1 NO 324211 B1 NO324211 B1 NO 324211B1 NO 19984852 A NO19984852 A NO 19984852A NO 984852 A NO984852 A NO 984852A NO 324211 B1 NO324211 B1 NO 324211B1
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- 201000010374 Down Syndrome Diseases 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- 206010044688 Trisomy 21 Diseases 0.000 claims description 6
- 206010012289 Dementia Diseases 0.000 claims description 5
- 239000008177 pharmaceutical agent Substances 0.000 claims 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 claims 2
- 208000037280 Trisomy Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT0071696A AT403803B (de) | 1996-04-19 | 1996-04-19 | Neue benzazepinderivate, diese enthaltende arzneimittel und verwendung derselben zum herstellen von arzneimitteln |
| PCT/AT1997/000074 WO1997040049A1 (fr) | 1996-04-19 | 1997-04-21 | Derives de benzazepine, medicaments contenant ces derives et leur utilisation pour produire des medicaments |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO984852D0 NO984852D0 (no) | 1998-10-16 |
| NO984852L NO984852L (no) | 1998-11-16 |
| NO324211B1 true NO324211B1 (no) | 2007-09-10 |
Family
ID=3497932
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19984852A NO324211B1 (no) | 1996-04-19 | 1998-10-16 | Nye benzazepinderivater, farmasoytisk middel inneholdende forbindelsene samt deres anvendelse ved fremstilling av medikamenter |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6638925B2 (fr) |
| EP (2) | EP1757608A1 (fr) |
| AT (1) | AT403803B (fr) |
| AU (1) | AU2498597A (fr) |
| BG (1) | BG64560B1 (fr) |
| CZ (1) | CZ300211B6 (fr) |
| IS (1) | IS4839A (fr) |
| NO (1) | NO324211B1 (fr) |
| PL (2) | PL189834B1 (fr) |
| RO (1) | RO120136B1 (fr) |
| TW (1) | TWI224595B (fr) |
| WO (1) | WO1997040049A1 (fr) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT403803B (de) * | 1996-04-19 | 1998-05-25 | Sanochemia Ltd | Neue benzazepinderivate, diese enthaltende arzneimittel und verwendung derselben zum herstellen von arzneimitteln |
| US7214686B2 (en) | 1997-06-30 | 2007-05-08 | Targacept, Inc. | Pharmaceutical compositions and methods for effecting dopamine release |
| AU1430099A (en) * | 1998-12-01 | 2000-06-19 | Sanochemia Pharmazeutika Aktiengesellschaft | Use of galanthamine and galanthamine derivatives in the case of acute functionalbrain damage |
| AU774867B2 (en) * | 1999-05-04 | 2004-07-08 | Neurosearch A/S | Heteroaryl diazabicycloalkanes, their preparation and use |
| KR100768245B1 (ko) * | 2000-03-31 | 2007-10-17 | 자노케미아 파마조이티카 악티엔게젤샤프트 | 신규한 갈란타민 유도체 및 유사체 |
| EP1181294B1 (fr) * | 2000-03-31 | 2004-03-31 | Sanochemia Pharmazeutika Aktiengesellschaft | Nouveaux derives et analogues de la galanthamine |
| US6852721B2 (en) * | 2000-05-25 | 2005-02-08 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
| US6440970B1 (en) * | 2000-05-25 | 2002-08-27 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
| US7060699B2 (en) | 2000-07-04 | 2006-06-13 | Neurosearch A/S | Aryl and heteroaryl diazabicycloalkanes, their preparation and use |
| YU30603A (sh) * | 2000-10-19 | 2006-05-25 | Pfizer Products Inc. | Derivati premošćenog piperazina |
| EP1340499A4 (fr) * | 2000-12-07 | 2006-05-03 | Astellas Pharma Inc | Nootropes |
| US6953801B2 (en) * | 2001-05-22 | 2005-10-11 | Neurogen Corporation | Melanin concentrating hormone receptor ligands: substituted 1-benzyl-4-aryl piperazine analogues |
| DE10129265A1 (de) * | 2001-06-18 | 2003-01-02 | Hf Arzneimittelforsch Gmbh | Wirkstoff-Kombination zur medikamentösen Sucht- oder Rauschmitteltherapie |
| JP4721386B2 (ja) * | 2001-07-10 | 2011-07-13 | 第一三共株式会社 | 新規ガランタミン類縁体 |
| DE10134038A1 (de) * | 2001-07-12 | 2003-02-06 | Hf Arzneimittelforsch Gmbh | Wirkstoff-Kombination zur medikamentösen Therapie der Nikotinabhängigkeit |
| WO2004005293A2 (fr) * | 2002-07-05 | 2004-01-15 | Targacept, Inc. | Composes diazaspirocycliques n-aryle et procedes de preparation et d'utilisation de ces derniers |
| WO2004009775A2 (fr) | 2002-07-19 | 2004-01-29 | Targacept, Inc. | Methodes et compositions associees a des sous-unites de recepteurs nicotiniques chimeriques |
| US7098331B2 (en) * | 2003-03-05 | 2006-08-29 | Targacept, Inc. | Arylvinylazacycloalkane compounds and methods of preparation and use thereof |
| JPWO2005027968A1 (ja) * | 2003-09-19 | 2007-11-15 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ダウン症候群治療剤 |
| AT414125B (de) * | 2003-09-29 | 2006-09-15 | Sanochemia Pharmazeutika Ag | Neue derivate des 4a,5,9,10,11,12-hexahydro- benzofuro(3a,3,2)(2) benzazepin, verfahren zu deren herstellung sowie deren verwendung zur herstellung von arzneimitteln |
| DK1678172T3 (da) * | 2003-10-15 | 2010-04-06 | Targacept Inc | Azabicykliske forbindelser til lindring af smerte og behandling af sygdomme i centralnervesystemet |
| AT500143A1 (de) * | 2004-04-22 | 2005-11-15 | Sanochemia Pharmazeutika Ag | Cholinesterase-inhibitoren in liposomen sowie deren herstellung und verwendung |
| US20070004679A1 (en) * | 2004-05-17 | 2007-01-04 | Nathalie Schlienger | Androgen receptor modulators and methods of treating disease using the same |
| WO2005115361A2 (fr) * | 2004-05-17 | 2005-12-08 | Acadia Pharmaceuticals Inc. | Modulateurs des recepteurs d'androgenes et methodes de traitement de maladies utilisant ceux-ci |
| US20050261278A1 (en) | 2004-05-21 | 2005-11-24 | Weiner David M | Selective serotonin receptor inverse agonists as therapeutics for disease |
| EP1802601A1 (fr) * | 2004-09-20 | 2007-07-04 | Targacept, Inc. | Composes d'azaspiroalcene et d'azaspiroalcane a activite de recepteurs nicotiniques cholinergiques |
| CN101137758B (zh) | 2004-11-03 | 2012-10-10 | 意力速分子诊断股份有限公司 | 均相分析物检测 |
| CN103091485A (zh) | 2004-11-03 | 2013-05-08 | 艾瑞斯国际有限公司 | 用于亲和分离的微泡 |
| UA88792C2 (ru) * | 2004-11-10 | 2009-11-25 | Таргасепт, Інк. | Гидроксибензоатные соли метаникотиновых соединений |
| US7459469B2 (en) | 2004-11-10 | 2008-12-02 | Targacept, Inc. | Hydroxybenzoate salts of metanicotine compounds |
| ITMI20042413A1 (it) * | 2004-12-17 | 2005-03-17 | Indena Spa | Processo per la preparazione di galantamina bromidrato |
| WO2006072818A2 (fr) * | 2005-01-04 | 2006-07-13 | Emcure Pharmaceuticals Limited | Procede pour preparer de la benzazepine |
| US20060173037A1 (en) * | 2005-01-10 | 2006-08-03 | Nathalie Schlienger | Aminophenyl derivatives as selective androgen receptor modulators |
| JP5203712B2 (ja) * | 2005-01-10 | 2013-06-05 | アカディア ファーマシューティカルズ インコーポレイテッド | 選択的アンドロゲン受容体モジュレータとしてのアミノフェニル誘導体 |
| WO2007016793A1 (fr) * | 2005-08-11 | 2007-02-15 | Universite De Montreal | La galantamine en tant que médicament neuroprotecteur pour les cellules ganglionnaires de la rétine |
| EP1917265B1 (fr) * | 2005-08-22 | 2010-09-29 | Targacept, Inc. | Diazatricycloalkanes substitues heteroaryle, procedes d'obtention et methodes d'utilisation |
| US20090253654A1 (en) * | 2005-09-22 | 2009-10-08 | Galantos Pharma Gmbh | Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases accompanied by cognitive impairment |
| US20070213318A1 (en) * | 2006-03-07 | 2007-09-13 | Galantos Pharma Gmbh | Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases accompanied by cognitive impairment |
| EP1777222A1 (fr) * | 2005-09-22 | 2007-04-25 | Galantos Pharma GmbH | Inhibiteurs de la cholinesterase avec une perméabilité améliorée de la barrière ématoencéphalique pour le traitement de troubles cognitifs |
| EP1968962A2 (fr) | 2005-12-14 | 2008-09-17 | Amgen Inc. | Derives diaza heterocycliques de sulfonamide et leurs utilisations |
| US8672732B2 (en) * | 2006-01-19 | 2014-03-18 | Schneider Electric It Corporation | Cooling system and method |
| CN100384850C (zh) * | 2006-04-14 | 2008-04-30 | 浙江大学 | 加兰他敏衍生物及制备方法和用途 |
| EP2357174A1 (fr) * | 2006-05-09 | 2011-08-17 | AstraZeneca AB | Sels de (2S)-(4E)-N-méthyl-5-[(5-isopropoxy)pyridin-3-yl]-4-pentèn-2-amine |
| TWI389889B (zh) * | 2006-05-09 | 2013-03-21 | Targacept Inc | （２ｓ）-（４ｅ）-ｎ-甲基-５-〔３-（５-異丙氧基吡啶）基〕-４-戊烯-２-胺之新穎多晶型 |
| SI2041088T1 (sl) | 2006-06-28 | 2014-05-30 | Amgen Inc. | Inhibitorji transporter-1 glicina |
| CL2007002684A1 (es) * | 2006-09-15 | 2008-06-27 | Astrazeneca Ab Targacept Inc | Combinacion que comprende un antipsicotico y (2s)-(4e)-n-metil-5-[3-(5-isopropoxipiridin)il]-4-penten-2-amina; composicion farmaceutica que la comprende; kit farmaceutico; y uso para tratar perjuicio cognitivo y/o trastorno psicoticos. |
| EP2112923A1 (fr) * | 2007-01-22 | 2009-11-04 | Targacept Inc. | Administration intranasale, buccale ou sublinguale d'analogues de métanicotine |
| US20100247617A1 (en) * | 2007-07-31 | 2010-09-30 | Targacept, Inc. | Transdermal Administration Of (2S)-(4E)-N-Methyl-5-(3-(5-Isopropoxypyridin)yl)-4-Penten-2-Amine |
| CN101883771A (zh) * | 2007-10-01 | 2010-11-10 | 科门蒂斯公司 | 作为α7-烟碱乙酰胆碱受体配体用于治疗阿尔茨海默氏病的奎宁环-4-基甲基1H-吲哚-3-甲酸酯衍生物 |
| JP5504253B2 (ja) | 2008-04-14 | 2014-05-28 | ニューロダイン ライフ サイエンス インコーポレイテッド | ヒトの脳疾患の治療のためのプロドラッグとしてのガランタミン誘導体 |
| MX2012006484A (es) | 2009-12-07 | 2012-08-01 | Targacept Inc | 3,6-diazabiciclo [3.1.1] heptanos como ligandos de receptores nicotinicos neuronales de acetilcolina. |
| SG185497A1 (en) | 2010-05-20 | 2012-12-28 | Astrazeneca Ab | New process for the preparation of aryl substituted olefinic amines |
| WO2013160728A1 (fr) | 2012-04-26 | 2013-10-31 | Alma Mater Studiorum - Universita' Di Bologna | Composés à double ciblage pour le traitement de la maladie d'alzheimer |
| CN104447767B (zh) * | 2013-09-24 | 2018-08-03 | 连云港金康医药科技有限公司 | 氮杂双环[3,2,1]辛烷衍生物及其应用 |
| US9434724B2 (en) | 2014-07-11 | 2016-09-06 | Alpharmagen, Llc | Quinuclidines for modulating alpha 7 activity |
| WO2017189834A1 (fr) * | 2016-04-29 | 2017-11-02 | New Mexico Tech Research Foundation | Méthodes pour le traitement d'un cancer résistant |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3947445A (en) | 1974-05-09 | 1976-03-30 | Stanford Research Institute | Diazabicyclooctanes and diazabicycloheptanes |
| US4663318A (en) * | 1986-01-15 | 1987-05-05 | Bonnie Davis | Method of treating Alzheimer's disease |
| KR100195399B1 (ko) | 1987-05-04 | 1999-06-15 | 보니데이비스 | 알쯔하이머 병 치료용 의약 |
| GB8800694D0 (en) | 1988-01-13 | 1988-02-10 | Pfizer Ltd | Antiarrhythmic agents |
| NL8800350A (nl) | 1988-02-12 | 1989-09-01 | Stichting Biomedical Research | Synthetische galanthamine-derivaten, werkwijze voor het bereiden daarvan, en farmaceutische samenstellingen. |
| US4954502A (en) * | 1988-06-10 | 1990-09-04 | Bristol-Myers Squibb Company | 1-indolyalkyl-4-(substituted-pyridinyl)piperazines |
| CA2012681A1 (fr) | 1989-03-31 | 1990-09-30 | Masayasu Okuhira | Derives de la quinolone, procedes de preparation et agents antibacteriens les renfermant |
| US5036153A (en) | 1989-05-11 | 1991-07-30 | Braish Tamim F | Preparation of 2,5-diazabicyclo[2.2.1]heptanes and intermediates |
| US4994460A (en) | 1989-06-01 | 1991-02-19 | Bristol-Myers Squibb Co. | Agents for treatment of brain ischemia |
| HUT61296A (en) | 1989-12-28 | 1992-12-28 | Upjohn Co | Process for producing substituted diaromatic compounds against aids and pharmaceutical compositions comprising same |
| HU213097B (en) | 1991-05-14 | 1997-02-28 | Egyt Gyogyszervegyeszeti Gyar | Process for producing phenylpiperazines |
| US5336675A (en) * | 1991-05-14 | 1994-08-09 | Ernir Snorrason | Method of treating mania in humans |
| US5153193A (en) * | 1991-10-01 | 1992-10-06 | Hoechst-Roussel Pharmaceuticals Incorporated | Carbamate derivatives of 4-amino-3-isoxazolidinones, 3-amino-1-hydroxypyrrolidin-2-ones and 1-amino-1-cyclopropanecarboxylic acid analogs |
| SK283420B6 (sk) | 1992-05-08 | 2003-07-01 | Pharmacia & Upjohn Company | Antimikrobiálne oxazolidinóny obsahujúce substituované diazínové skupiny |
| US6316439B1 (en) | 1993-10-15 | 2001-11-13 | Aventis Pharamaceuticals Inc. | Galanthamine derivatives as acetylcholinesterase inhibitors |
| US6323196B1 (en) | 1993-10-15 | 2001-11-27 | Aventis Pharmaceuticals Inc. | Galanthamine derivatives as acetylcholinesterase inhibitors |
| US6323195B1 (en) * | 1993-10-15 | 2001-11-27 | Aventis Pharmaceuticals Inc. | Galanthamine derivatives as acetylcholinesterase inhibitors |
| US5428159A (en) | 1994-04-08 | 1995-06-27 | Ciba-Geigy Corporation | Method of manufacture of (-)-galanthamine in high yield and purity substantially free of epigalanthamine |
| ES2106700T3 (es) * | 1994-10-21 | 2000-05-16 | Sanochemia Pharmazeutika Ag | Procedimiento para la preparacion de derivados de la 4a,5,9,10,11,12-hexahidro-6h-benzofuro(3a,3,2-ef)(2)benzacepinas. |
| US6407229B1 (en) * | 1994-10-21 | 2002-06-18 | Sanochemia Pharmazeutika Ag | Processes for the preparation of derivatives of 4a,5,9,10,11,12-hexahydro-6H-benzofuro-[3a,3,2-ef][2] benzazapine |
| AT401058B (de) | 1994-10-21 | 1996-06-25 | Waldheim Pharmazeutika Gmbh | Verfahren zum herstellen von derivaten des 4a,5, 9,10,11,12,-hexahydro-6h-benzofuro(3a,-3,2-ef) (2)benzazepins |
| GB9519268D0 (en) | 1995-09-21 | 1995-11-22 | Chiroscience Ltd | Preparation of alkaloids |
| AT403803B (de) * | 1996-04-19 | 1998-05-25 | Sanochemia Ltd | Neue benzazepinderivate, diese enthaltende arzneimittel und verwendung derselben zum herstellen von arzneimitteln |
| AU1430099A (en) | 1998-12-01 | 2000-06-19 | Sanochemia Pharmazeutika Aktiengesellschaft | Use of galanthamine and galanthamine derivatives in the case of acute functionalbrain damage |
| AT414125B (de) | 2003-09-29 | 2006-09-15 | Sanochemia Pharmazeutika Ag | Neue derivate des 4a,5,9,10,11,12-hexahydro- benzofuro(3a,3,2)(2) benzazepin, verfahren zu deren herstellung sowie deren verwendung zur herstellung von arzneimitteln |
-
1996
- 1996-04-19 AT AT0071696A patent/AT403803B/de not_active IP Right Cessation
-
1997
- 1997-04-21 AU AU24985/97A patent/AU2498597A/en not_active Abandoned
- 1997-04-21 WO PCT/AT1997/000074 patent/WO1997040049A1/fr not_active Application Discontinuation
- 1997-04-21 RO RO98-01487A patent/RO120136B1/ro unknown
- 1997-04-21 EP EP06025028A patent/EP1757608A1/fr not_active Withdrawn
- 1997-04-21 PL PL97329411A patent/PL189834B1/pl not_active IP Right Cessation
- 1997-04-21 EP EP97916263A patent/EP0897387A1/fr not_active Ceased
- 1997-04-21 US US09/242,339 patent/US6638925B2/en not_active Expired - Fee Related
- 1997-04-21 PL PL97361697A patent/PL190032B1/pl not_active IP Right Cessation
- 1997-04-21 CZ CZ0332498A patent/CZ300211B6/cs not_active IP Right Cessation
- 1997-05-09 TW TW086106195A patent/TWI224595B/zh not_active IP Right Cessation
-
1998
- 1998-08-28 IS IS4839A patent/IS4839A/is unknown
- 1998-10-12 BG BG102836A patent/BG64560B1/bg unknown
- 1998-10-16 NO NO19984852A patent/NO324211B1/no not_active IP Right Cessation
-
2003
- 2003-08-26 US US10/647,283 patent/US7101890B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| PL189834B1 (pl) | 2005-09-30 |
| AT403803B (de) | 1998-05-25 |
| US6638925B2 (en) | 2003-10-28 |
| PL190032B1 (pl) | 2005-10-31 |
| IS4839A (is) | 1998-08-28 |
| WO1997040049A1 (fr) | 1997-10-30 |
| US7101890B2 (en) | 2006-09-05 |
| EP1757608A1 (fr) | 2007-02-28 |
| US20040067974A1 (en) | 2004-04-08 |
| RO120136B1 (ro) | 2005-09-30 |
| NO984852D0 (no) | 1998-10-16 |
| ATA71696A (de) | 1997-10-15 |
| NO984852L (no) | 1998-11-16 |
| EP0897387A1 (fr) | 1999-02-24 |
| BG64560B1 (bg) | 2005-07-29 |
| US20030092700A1 (en) | 2003-05-15 |
| PL329411A1 (en) | 1999-03-29 |
| CZ300211B6 (cs) | 2009-03-18 |
| AU2498597A (en) | 1997-11-12 |
| CZ332498A3 (cs) | 1999-05-12 |
| TWI224595B (en) | 2004-12-01 |
| BG102836A (en) | 1999-09-30 |
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