HRP20030499A2 - Diphenyl azetidinone derivatives, method for the production thereof, medicaments containing these compounds, and their use - Google Patents
Diphenyl azetidinone derivatives, method for the production thereof, medicaments containing these compounds, and their use Download PDFInfo
- Publication number
- HRP20030499A2 HRP20030499A2 HR20030499A HRP20030499A HRP20030499A2 HR P20030499 A2 HRP20030499 A2 HR P20030499A2 HR 20030499 A HR20030499 A HR 20030499A HR P20030499 A HRP20030499 A HR P20030499A HR P20030499 A2 HRP20030499 A2 HR P20030499A2
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- Prior art keywords
- alkyl
- phenyl
- compounds
- agonists
- butyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 126
- 239000003814 drug Substances 0.000 title claims description 15
- 238000000034 method Methods 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- VDOXIAUNJCHYRC-UHFFFAOYSA-N 1,3-diphenylazetidin-2-one Chemical class O=C1C(C=2C=CC=CC=2)CN1C1=CC=CC=C1 VDOXIAUNJCHYRC-UHFFFAOYSA-N 0.000 title description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 90
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
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Classifications
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- 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10064402A DE10064402A1 (de) | 2000-12-21 | 2000-12-21 | Diphenylazetidinonderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
DE2001154520 DE10154520A1 (de) | 2001-11-07 | 2001-11-07 | Diphenylazetidinonderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
PCT/EP2001/014532 WO2002050068A1 (de) | 2000-12-21 | 2001-12-11 | Diphenylazetidinonderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20030499A2 true HRP20030499A2 (en) | 2005-04-30 |
Family
ID=26008045
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20030499A HRP20030499A2 (en) | 2000-12-21 | 2003-06-18 | Diphenyl azetidinone derivatives, method for the production thereof, medicaments containing these compounds, and their use |
Country Status (24)
Country | Link |
---|---|
US (1) | US6498156B2 (pl) |
EP (1) | EP1345932B1 (pl) |
JP (1) | JP2004516293A (pl) |
KR (1) | KR20030061462A (pl) |
CN (1) | CN1222522C (pl) |
AR (1) | AR034282A1 (pl) |
AT (1) | ATE342899T1 (pl) |
AU (2) | AU1917302A (pl) |
BR (1) | BR0116482A (pl) |
CA (1) | CA2431985A1 (pl) |
CZ (1) | CZ20031731A3 (pl) |
DE (1) | DE50111293D1 (pl) |
EE (1) | EE200300237A (pl) |
HK (1) | HK1059936A1 (pl) |
HR (1) | HRP20030499A2 (pl) |
HU (1) | HUP0401067A2 (pl) |
IL (1) | IL156552A0 (pl) |
MX (1) | MXPA03005018A (pl) |
NO (1) | NO20032733L (pl) |
NZ (1) | NZ526592A (pl) |
PL (1) | PL362173A1 (pl) |
SK (1) | SK7812003A3 (pl) |
WO (1) | WO2002050068A1 (pl) |
YU (1) | YU46903A (pl) |
Families Citing this family (61)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SK7822003A3 (en) * | 2000-12-21 | 2003-12-02 | Aventis Pharma Gmbh | Novel 1,2-diphenzylazetidinones, method for producing the same, medicaments containing said compounds, and the use thereof for treating disorders of the lipid metabolism |
SK9502003A3 (en) * | 2001-01-26 | 2003-12-02 | Schering Corp | Combinations of sterol absorption inhibitor(s) with blood modifier(s) for treating vascular conditions |
AR032643A1 (es) * | 2001-01-26 | 2003-11-19 | Schering Corp | Combinaciones de inhibidor(es) de absorcion de esterol con agente(s) cardiovascular(es) para el tratamiento de condiciones vasculares |
EP1353695A2 (en) * | 2001-01-26 | 2003-10-22 | Schering Corporation | Combinations of nicotinic acid and derivatives thereof and sterol absorption inhibitor(s) and treatments for vascular indications |
CN100509058C (zh) * | 2001-01-26 | 2009-07-08 | 先灵公司 | 过氧化物酶体增殖物激活受体(ppar)活化剂和甾醇吸收抑制剂的组合药以及对于血管适应症的治疗 |
DE60221798T2 (de) * | 2001-01-26 | 2008-06-05 | Schering Corp. | Kombinationen von gallensäure sequestriermitteln und hemmern der sterol absorption zur behandlung von kardiovaskulären indikationen |
RS11104A (en) * | 2001-08-22 | 2006-12-15 | Sanofi Aventis Deutschland Gmbh. | Combined preparations,containing 1,4- benzothiepine-1,1- dioxide derivatives and other active substances, and the use thereof |
US7053080B2 (en) * | 2001-09-21 | 2006-05-30 | Schering Corporation | Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors |
US20030119808A1 (en) * | 2001-09-21 | 2003-06-26 | Schering Corporation | Methods of treating or preventing cardiovascular conditions while preventing or minimizing muscular degeneration side effects |
US7056906B2 (en) | 2001-09-21 | 2006-06-06 | Schering Corporation | Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women |
ES2272776T3 (es) * | 2001-09-21 | 2007-05-01 | Schering Corporation | Tratamiento de xantomas con derivados de azetidinona como inhibidores de la absorcion de esterol. |
US7176194B2 (en) | 2002-06-19 | 2007-02-13 | Sanofi-Aventis Deutschland Gmbh | Ring-substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use |
DE10227507A1 (de) * | 2002-06-19 | 2004-01-08 | Aventis Pharma Deutschland Gmbh | Kationisch substituierte Diphenylazetidinone, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
US7176193B2 (en) | 2002-06-19 | 2007-02-13 | Sanofi-Aventis Deutschland Gmbh | Acid-group-substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use |
US7671047B2 (en) | 2002-06-19 | 2010-03-02 | Sanofi-Aventis Deutschland Gmbh | Cationically substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use |
DE10227508A1 (de) * | 2002-06-19 | 2004-01-08 | Aventis Pharma Deutschland Gmbh | Säuregruppen-substituierte Diphenylazetidinone, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
GB0215579D0 (en) * | 2002-07-05 | 2002-08-14 | Astrazeneca Ab | Chemical compounds |
JP2006501205A (ja) * | 2002-07-30 | 2006-01-12 | カリキオン インコーポレイテッド | エゼチミブ組成物、並びにコレステロールに関連した良性および悪性の腫瘍を治療する方法 |
MXPA05009501A (es) | 2003-03-07 | 2005-10-18 | Schering Corp | Compuestos de azetidinona sustituidos, formulaciones y usos de los mismos para el tratamiento de hipercolesterolemia. |
MXPA05009503A (es) | 2003-03-07 | 2005-10-18 | Schering Corp | Compuestos de azetidinona sustituidos, formulaciones y usos de los mismos para el tratamiento de hipercolesterolemia. |
US9060993B2 (en) * | 2003-05-09 | 2015-06-23 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treating cancer |
US20070072812A1 (en) * | 2003-08-25 | 2007-03-29 | Microbia, Inc. | Quaternary salt derivatives of 1,4-diphenylazetidin-2-ones |
US8987322B2 (en) * | 2003-11-04 | 2015-03-24 | Circ Pharma Research And Development Limited | Pharmaceutical formulations for carrier-mediated transport statins and uses thereof |
EP1918000A2 (en) | 2003-11-05 | 2008-05-07 | Schering Corporation | Combinations of lipid modulating agents and substituted azetidinones and treatments for vascular conditions |
JP4688819B2 (ja) | 2003-12-23 | 2011-05-25 | アストラゼネカ アクチボラグ | コレステロール吸収阻害活性を有するジフェニルアゼチジノン誘導体 |
EA010373B1 (ru) * | 2004-01-20 | 2008-08-29 | Панацея Биотек Лтд. | Фармацевтические композиции, содержащие высшие первичные спирты и эзетимиб, и способ их получения |
KR20060129082A (ko) | 2004-03-05 | 2006-12-14 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 부작용을 최소화하면서 과지질혈증 및 과콜레스테롤혈증과연관된 질환 또는 질병의 치료 방법 |
CA2581596A1 (en) * | 2004-09-29 | 2006-04-13 | Schering Corporation | Combinations of substituted azetidonones and cb1 antagonists |
WO2006047302A1 (en) * | 2004-10-21 | 2006-05-04 | Transtech Pharma, Inc. | Bissulfonamide compounds as agonists of galr1, compositions, and methods of use |
ES2435790T3 (es) | 2004-12-03 | 2013-12-23 | Intervet International B.V. | Piperazinas sustituidas como antagonistas de CB1 |
TW200726746A (en) * | 2005-05-06 | 2007-07-16 | Microbia Inc | Processes for production of 4-biphenylylazetidin-2-ones |
EA200702450A1 (ru) * | 2005-05-09 | 2008-04-28 | Майкробиа, Инк. | Металлоорганические бензолфосфонатные связующие вещества |
EA200702464A1 (ru) * | 2005-05-11 | 2008-04-28 | Майкробиа, Инк. | Способы получения фенольных 4-бифенилилазетидин-2-онов |
BRPI0611415A2 (pt) * | 2005-05-25 | 2010-09-08 | Microbia Inc | ácidos fosfÈnicos de 4-(bifenilil)azetidin-2-ona e processo para a produção dos mesmos |
WO2007001975A1 (en) * | 2005-06-20 | 2007-01-04 | Schering Corporation | Piperidine derivatives useful as histamine h3 antagonists |
SA06270191B1 (ar) | 2005-06-22 | 2010-03-29 | استرازينيكا ايه بي | مشتقات من 2- أزيتيدينون جديدة باعتبارها مثبطات لامتصاص الكوليسترول لعلاج حالات فرط نسبة الدهون في الدم |
US20080253985A1 (en) * | 2005-10-18 | 2008-10-16 | Wisler Gerald L | Compositions for Lowering Serum Cholesterol and/or Triglycerides |
AR059021A1 (es) * | 2006-01-18 | 2008-03-05 | Schering Corp | Moduladores de receptores cannabinoides |
AR060623A1 (es) | 2006-04-27 | 2008-07-02 | Astrazeneca Ab | Compuestos derivados de 2-azetidinona y un metodo de preparacion |
EP2061767B1 (de) | 2006-08-08 | 2014-12-17 | Sanofi | Arylaminoaryl-alkyl-substituierte Imidazolidin-2,4-dione, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Arzneimittel und ihre Verwendung |
MX2009002398A (es) * | 2006-09-05 | 2009-03-16 | Schering Corp | Combinaciones farmaceuticas para manejo de lipidos y en el tratamiento de aterosclerosis y estatosis hepatica. |
WO2008039829A2 (en) * | 2006-09-26 | 2008-04-03 | Ironwood Pharmaceuticals, Inc. | Diphenylheterocycle cholesterol absorption inhibitors |
DE102007002260A1 (de) * | 2007-01-16 | 2008-07-31 | Sanofi-Aventis | Verwendung von substituierten Pyranonsäurederivaten zur Herstellung von Medikamenten zur Behandlung des Metabolischen Syndroms |
WO2008130616A2 (en) * | 2007-04-19 | 2008-10-30 | Schering Corporation | Diaryl morpholines as cb1 modulators |
WO2009005671A2 (en) * | 2007-06-28 | 2009-01-08 | Schering Corporation | Substituted piperazines as cb1 antagonists |
MX2010000334A (es) * | 2007-06-28 | 2010-04-22 | Intervet Int Bv | Piperazinas sustituidas como antagonistas de cannabinoides 1. |
EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
DE102007054497B3 (de) * | 2007-11-13 | 2009-07-23 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung |
US20090312302A1 (en) * | 2008-06-17 | 2009-12-17 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating nonalcoholic fatty liver disease-associated disorders |
US8470841B2 (en) | 2008-07-09 | 2013-06-25 | Sanofi | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
WO2010100255A1 (en) | 2009-03-06 | 2010-09-10 | Lipideon Biotechnology Ag | Pharmaceutical hypocholesterolemic compositions |
CN101993403B (zh) | 2009-08-11 | 2012-07-11 | 浙江海正药业股份有限公司 | 氮杂环丁酮类化合物及医药应用 |
RU2012111354A (ru) | 2009-08-26 | 2013-10-10 | Санофи | Новые кристаллические гидраты фторгликозидов, содержащие их фармацевтические препараты и их использование |
WO2011157827A1 (de) | 2010-06-18 | 2011-12-22 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
EP2683700B1 (de) | 2011-03-08 | 2015-02-18 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
US8710050B2 (en) | 2011-03-08 | 2014-04-29 | Sanofi | Di and tri- substituted oxathiazine derivatives, method for the production, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
WO2012120053A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
CN102746249B (zh) * | 2012-07-07 | 2013-12-25 | 山东诚创医药技术开发有限公司 | 一种依折麦布中间体的纯化精制方法 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5631365A (en) * | 1993-09-21 | 1997-05-20 | Schering Corporation | Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents |
MX9606319A (es) * | 1994-06-20 | 1997-05-31 | Schering Corp | Compuestos de acetidinonas sustituidas utiles como agentes hipocolesterolemicos. |
US5994391A (en) * | 1994-09-13 | 1999-11-30 | G.D. Searle And Company | Benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake |
ATE199718T1 (de) * | 1994-09-13 | 2001-03-15 | Monsanto Co | Benzothepines mit wirkung als inhibitoren des gallensäuretransports und der taurocholate- aufnahme |
US5656624A (en) * | 1994-12-21 | 1997-08-12 | Schering Corporation | 4-[(heterocycloalkyl or heteroaromatic)-substituted phenyl]-2-azetidinones useful as hypolipidemic agents |
US5756470A (en) | 1996-10-29 | 1998-05-26 | Schering Corporation | Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents |
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2000
- 2000-12-11 IL IL15655200A patent/IL156552A0/xx unknown
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2001
- 2001-12-11 EP EP01271371A patent/EP1345932B1/de not_active Expired - Lifetime
- 2001-12-11 CA CA002431985A patent/CA2431985A1/en not_active Abandoned
- 2001-12-11 AT AT01271371T patent/ATE342899T1/de not_active IP Right Cessation
- 2001-12-11 PL PL01362173A patent/PL362173A1/pl not_active Application Discontinuation
- 2001-12-11 CZ CZ20031731A patent/CZ20031731A3/cs unknown
- 2001-12-11 CN CNB018210449A patent/CN1222522C/zh not_active Expired - Fee Related
- 2001-12-11 AU AU1917302A patent/AU1917302A/xx active Pending
- 2001-12-11 DE DE50111293T patent/DE50111293D1/de not_active Expired - Lifetime
- 2001-12-11 MX MXPA03005018A patent/MXPA03005018A/es active IP Right Grant
- 2001-12-11 EE EEP200300237A patent/EE200300237A/xx unknown
- 2001-12-11 KR KR10-2003-7008330A patent/KR20030061462A/ko not_active Application Discontinuation
- 2001-12-11 HU HU0401067A patent/HUP0401067A2/hu unknown
- 2001-12-11 YU YU46903A patent/YU46903A/sh unknown
- 2001-12-11 JP JP2002551564A patent/JP2004516293A/ja not_active Abandoned
- 2001-12-11 SK SK781-2003A patent/SK7812003A3/sk unknown
- 2001-12-11 BR BR0116482-1A patent/BR0116482A/pt not_active IP Right Cessation
- 2001-12-11 NZ NZ526592A patent/NZ526592A/en unknown
- 2001-12-11 WO PCT/EP2001/014532 patent/WO2002050068A1/de not_active Application Discontinuation
- 2001-12-11 AU AU2002219173A patent/AU2002219173B2/en not_active Expired - Fee Related
- 2001-12-19 US US10/021,028 patent/US6498156B2/en not_active Expired - Lifetime
- 2001-12-19 AR ARP010105906A patent/AR034282A1/es unknown
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2003
- 2003-06-16 NO NO20032733A patent/NO20032733L/no not_active Application Discontinuation
- 2003-06-18 HR HR20030499A patent/HRP20030499A2/hr not_active Application Discontinuation
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Also Published As
Publication number | Publication date |
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IL156552A0 (en) | 2004-01-04 |
CN1222522C (zh) | 2005-10-12 |
AR034282A1 (es) | 2004-02-18 |
SK7812003A3 (en) | 2004-01-08 |
PL362173A1 (pl) | 2004-10-18 |
NZ526592A (en) | 2004-11-26 |
US6498156B2 (en) | 2002-12-24 |
EP1345932A1 (de) | 2003-09-24 |
AU1917302A (en) | 2002-07-01 |
YU46903A (sh) | 2006-05-25 |
DE50111293D1 (de) | 2006-11-30 |
NO20032733L (no) | 2003-08-14 |
US20020128252A1 (en) | 2002-09-12 |
JP2004516293A (ja) | 2004-06-03 |
ATE342899T1 (de) | 2006-11-15 |
NO20032733D0 (no) | 2003-06-16 |
HK1059936A1 (en) | 2004-07-23 |
CZ20031731A3 (cs) | 2003-09-17 |
WO2002050068A1 (de) | 2002-06-27 |
CA2431985A1 (en) | 2002-06-27 |
KR20030061462A (ko) | 2003-07-18 |
MXPA03005018A (es) | 2003-09-25 |
HUP0401067A2 (hu) | 2004-09-28 |
CN1481381A (zh) | 2004-03-10 |
BR0116482A (pt) | 2004-02-03 |
AU2002219173B2 (en) | 2006-06-22 |
EE200300237A (et) | 2003-08-15 |
EP1345932B1 (de) | 2006-10-18 |
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