TW200426147A - Quinazolines useful as modulators of ion channels - Google Patents
Quinazolines useful as modulators of ion channels Download PDFInfo
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- TW200426147A TW200426147A TW093105557A TW93105557A TW200426147A TW 200426147 A TW200426147 A TW 200426147A TW 093105557 A TW093105557 A TW 093105557A TW 93105557 A TW93105557 A TW 93105557A TW 200426147 A TW200426147 A TW 200426147A
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Classifications
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- 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
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D471/04—Ortho-condensed systems
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- 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
- C07D487/04—Ortho-condensed systems
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Families Citing this family (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7713983B2 (en) * | 2003-03-03 | 2010-05-11 | Vertex Pharmaceuticals Incorporated | Quinazolines useful as modulators of ion channels |
| US7763627B2 (en) * | 2003-04-09 | 2010-07-27 | Exelixis, Inc. | Tie-2 modulators and methods of use |
| BRPI0411514A (pt) * | 2003-06-20 | 2006-08-01 | Coley Pharm Gmbh | antagonistas de receptor toll-like de molécula pequena |
| AR045037A1 (es) * | 2003-07-10 | 2005-10-12 | Aventis Pharma Sa | Tetrahidro-1h-pirazolo [3,4-c] piridinas sustituidas, composiciones que las contienen y su utilizacion. |
| JP2007510745A (ja) * | 2003-11-10 | 2007-04-26 | シンタ ファーマシューティカルズ コーポレーション | 縮合複素環式化合物 |
| US8283354B2 (en) | 2004-09-02 | 2012-10-09 | Vertex Pharmaceuticals Incorporated | Quinazolines useful as modulators of ion channels |
| CN101068794B (zh) * | 2004-09-02 | 2012-12-19 | 沃泰克斯药物股份有限公司 | 可用作离子通道调控剂的喹唑啉 |
| US7928107B2 (en) * | 2004-09-02 | 2011-04-19 | Vertex Pharmaceuticals Incorporated | Quinazolines useful as modulators of ion channels |
| US7718658B2 (en) * | 2004-09-02 | 2010-05-18 | Vertex Pharmaceuticals Incorporated | Quinazolines useful as modulators of ion channels |
| RU2007127315A (ru) * | 2004-12-17 | 2009-01-27 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Способы получения 4-аминохиназолинов |
| US8252806B2 (en) | 2005-03-14 | 2012-08-28 | Neurosearch A/S | Potassium channel modulating agents and their medical use |
| JP5112297B2 (ja) * | 2005-05-20 | 2013-01-09 | バーテックス ファーマシューティカルズ インコーポレイテッド | イオンチャネルのモジュレーターとして有用なキノリン誘導体 |
| FR2891829A1 (fr) * | 2005-10-12 | 2007-04-13 | Sanofi Aventis Sa | Derives de la 4-amino-quinazoline, leur preparation et leur application en therapeutique |
| GB0522715D0 (en) | 2005-11-08 | 2005-12-14 | Helperby Therapeutics Ltd | New use |
| ATE540033T1 (de) * | 2005-11-14 | 2012-01-15 | Vertex Pharma | Als modulatoren von spannungsgesteuerten ionenkanälen geeignete chinazoline |
| CA2630617C (en) | 2005-11-23 | 2014-03-25 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
| US20070197509A1 (en) * | 2005-12-21 | 2007-08-23 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
| WO2007115408A1 (en) * | 2006-04-10 | 2007-10-18 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
| AU2007245496A1 (en) | 2006-04-26 | 2007-11-08 | Cancer Research Technology Limited | Amino-ethyl-amino-aryl (AEAA) compounds and their use |
| JP2009539988A (ja) * | 2006-06-12 | 2009-11-19 | バーテックス ファーマシューティカルズ インコーポレイテッド | イオンチャネルの調節因子として有用なチエノピリミジン |
| CA2661307C (en) * | 2006-08-22 | 2016-07-19 | Technion Research And Development Foundation Ltd. | Heterocyclic derivatives binding to the peripheral-type benzodiazepine receptor (pbr) |
| CA2665398A1 (en) | 2006-10-03 | 2008-04-10 | Neurosearch A/S | Indazolyl derivatives useful as potassium channel modulating agents |
| MX2009003673A (es) | 2006-10-04 | 2009-04-22 | Pfizer Prod Inc | Derivados de piridido[4,3-d]pirimidin-4(3h)-ona como antagonistas de los receptores de calcio. |
| AU2007328336B2 (en) * | 2006-12-01 | 2014-04-17 | President And Fellows Of Harvard College | Compounds and methods for enzyme-mediated tumor imaging and therapy |
| MX2009010127A (es) * | 2007-03-22 | 2009-11-05 | Vertex Pharma | Compuestos utiles como inhibidores de janus cinasas. |
| PT2182950T (pt) * | 2007-05-17 | 2017-09-11 | Helperby Therapeutics Ltd | Uso de compostos 4-(pirrolidin-1-il)quinolina para eliminação de microrganismos clinicamente latentes |
| WO2008157500A1 (en) * | 2007-06-17 | 2008-12-24 | Kalypsys, Inc. | Aminoquinazoline cannabinoid receptor modulators for treatment of disease |
| US20090023773A1 (en) * | 2007-06-27 | 2009-01-22 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
| WO2009053694A1 (en) * | 2007-10-24 | 2009-04-30 | Cancer Research Technology Limited | Therapeutic oxy-phenyl-aryl compounds and their use |
| KR101337163B1 (ko) | 2008-11-14 | 2013-12-05 | 에프. 호프만-라 로슈 아게 | Nk3 수용체 길항제로서 퀴나졸린 유도체 |
| WO2010135568A1 (en) * | 2009-05-22 | 2010-11-25 | Exelixis, Inc. | Benzoxazepines as inhibitors of mtor and their use to treat cancer |
| US8648066B2 (en) * | 2009-05-22 | 2014-02-11 | Exelixis, Inc. | Benzoxazepines as inhibitors of PI3K/mTOR and methods of their use and manufacture |
| WO2010151595A1 (en) * | 2009-06-26 | 2010-12-29 | Schering Corporation | Pyrrolo-benzo-1,4-diazines useful as sodium channel blockers |
| US20110053916A1 (en) | 2009-08-14 | 2011-03-03 | Vertex Pharmaceuticals Incorporated | Pyrimidine compounds as tuberculosis inhibitors |
| ES2900504T3 (es) * | 2009-09-03 | 2022-03-17 | Bristol Myers Squibb Co | Quinazolinas como inhibidores de los canales iónicos de potasio |
| AR079814A1 (es) | 2009-12-31 | 2012-02-22 | Otsuka Pharma Co Ltd | Compuestos heterociclicos, composiciones farmaceuticas que los contienen y sus usos |
| TW201139406A (en) * | 2010-01-14 | 2011-11-16 | Glaxo Group Ltd | Voltage-gated sodium channel blockers |
| US8609672B2 (en) | 2010-08-27 | 2013-12-17 | University Of The Pacific | Piperazinylpyrimidine analogues as protein kinase inhibitors |
| BR112013008374A2 (pt) | 2010-10-05 | 2016-06-14 | Purdue Pharma Lp | composto de quinazolina como bloqueador do canal de sódio |
| JP5937102B2 (ja) | 2010-12-14 | 2016-06-22 | エレクトロフォレティクス リミテッド | カゼインキナーゼ1デルタ(ck1デルタ)阻害剤 |
| WO2013070852A2 (en) * | 2011-11-08 | 2013-05-16 | Emory University | Compounds and compositions used to epigenetically transform cells and methods related thereto |
| CN103360382B (zh) * | 2012-03-26 | 2016-04-27 | 中国科学院福建物质结构研究所 | 喹唑啉衍生物及其用途 |
| JP6311603B2 (ja) * | 2012-06-22 | 2018-04-18 | 住友化学株式会社 | 縮合複素環化合物 |
| US20150259649A1 (en) * | 2012-11-08 | 2015-09-17 | Emory University | Cellular compositions used to restore stem cell or progenitor cell function and methods related thereto |
| US9073878B2 (en) | 2012-11-21 | 2015-07-07 | Zenith Epigenetics Corp. | Cyclic amines as bromodomain inhibitors |
| US9765039B2 (en) | 2012-11-21 | 2017-09-19 | Zenith Epigenetics Ltd. | Biaryl derivatives as bromodomain inhibitors |
| CA2895905A1 (en) | 2012-12-21 | 2014-06-26 | Zenith Epigenetics Corp. | Novel heterocyclic compounds as bromodomain inhibitors |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| EP2970199A1 (en) * | 2013-03-11 | 2016-01-20 | Bristol-Myers Squibb Company | Isoquinolines as potassium ion channel inhibitors |
| US9242966B2 (en) * | 2013-03-11 | 2016-01-26 | Bristol-Myers Squibb Company | Phthalazines as potassium ion channel inhibitors |
| WO2015004533A2 (en) | 2013-06-21 | 2015-01-15 | Zenith Epigenetics Corp. | Novel substituted bicyclic compounds as bromodomain inhibitors |
| PL3010503T3 (pl) | 2013-06-21 | 2020-08-24 | Zenith Epigenetics Ltd. | Nowe bicykliczne inhibitory bromodomen |
| EP3027604B1 (en) | 2013-07-31 | 2019-02-20 | Zenith Epigenetics Ltd. | Novel quinazolinones as bromodomain inhibitors |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| EP3062795A4 (en) * | 2013-11-01 | 2017-05-31 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CN103755649A (zh) * | 2013-12-31 | 2014-04-30 | 李增 | 一种喹唑啉衍生物及其作为血管生成抑制剂的应用 |
| US9676757B2 (en) * | 2014-02-27 | 2017-06-13 | Merck Patent Gmbh | Heterocyclic compounds as NaV channel inhibitors and uses thereof |
| JP6498695B2 (ja) | 2014-04-23 | 2019-04-10 | テクニオン・リサーチ・アンド・ディベロップメント・ファウンデーション・リミテッド | キナゾリン骨格系の化合物、医薬組成物およびその使用方法 |
| EP3206689B1 (en) * | 2014-10-14 | 2021-12-08 | La Jolla Institute of Allergy & Immunology | Inhibitors of low molecular weight protein tyrosine phosphatase and uses thereof |
| US10710992B2 (en) | 2014-12-01 | 2020-07-14 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| EP3227280B1 (en) | 2014-12-01 | 2019-04-24 | Zenith Epigenetics Ltd. | Substituted pyridines as bromodomain inhibitors |
| EP3226868A4 (en) * | 2014-12-05 | 2018-08-15 | Subramaniam Ananthan | Novel quinazolines as biogenic amine transport modulators |
| CN107207474B (zh) | 2014-12-11 | 2021-05-07 | 恒翼生物医药科技(上海)有限公司 | 被取代的杂环作为溴结构域抑制剂 |
| US10231953B2 (en) | 2014-12-17 | 2019-03-19 | Zenith Epigenetics Ltd. | Inhibitors of bromodomains |
| CN107438598A (zh) * | 2015-01-20 | 2017-12-05 | 米伦纽姆医药公司 | 喹唑啉和喹啉化合物及其用途 |
| WO2017075222A1 (en) * | 2015-10-30 | 2017-05-04 | Lieber Institute For Brain Development | Treatment of neurological and neurodevelopmental diseases and disorders associated with aberrant ion channel expression and activity |
| KR102327053B1 (ko) * | 2017-03-16 | 2021-11-17 | 기초과학연구원 | 퀴나졸린, 퀴놀린 유도체 및 egfr 키나제 억제제로서의 용도 |
| WO2018204176A1 (en) | 2017-05-01 | 2018-11-08 | Sanford Burnham Prebys Medical Discovery Institute | Inhibitors of low molecular weight protein tyrosine phosphatase (lmptp) and uses thereof |
| WO2019027765A1 (en) * | 2017-08-02 | 2019-02-07 | Northwestern University | SUBSTITUTED FUSED PYRIMIDINE COMPOUNDS AND USES THEREOF |
| CN111867549B (zh) * | 2018-02-02 | 2024-01-05 | 安捷伦科技有限公司 | 用于使用封闭的2-aa进行聚糖分析的方法和试剂盒 |
| JP7633676B2 (ja) | 2018-07-26 | 2025-02-20 | ドメイン・セラピューティクス | 置換キナゾリノン誘導体、及びmGluR4のポジティブアロステリック調節剤としてのその使用 |
| AU2020204717B2 (en) * | 2019-01-03 | 2025-01-16 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Methods and materials for increasing transcription factor EB polypeptide levels |
| WO2021114313A1 (en) * | 2019-12-14 | 2021-06-17 | Shanghai East Hospital | Ion channel antagonists/blockers and uses thereof |
| WO2024258849A2 (en) * | 2023-06-13 | 2024-12-19 | The Trustees Of Indiana University | Small molecule antiviral drug treatment for human papillomavirus infections |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE119051C (enExample) | ||||
| NL292083A (enExample) * | 1962-09-18 | |||
| US3340260A (en) | 1962-12-03 | 1967-09-05 | Ciba Geigy Corp | 4-amino-pyrimidines |
| GB1199768A (en) * | 1966-10-31 | 1970-07-22 | Pfizer & Co C | Nitrogen Heterocycles and process for their preparation |
| US3637693A (en) | 1968-07-12 | 1972-01-25 | Du Pont | Hydroxyarylquinazolines and their use as uv-absorbers |
| US3705898A (en) * | 1970-01-26 | 1972-12-12 | Morton Norwich Products Inc | Certain 4 - amino - 2-(5-nitro-2-thienyl) quinazolines and the intermediate 4 - chloro-(5 - nitro-2-thienyl)quinazolines therefor |
| DE2121031A1 (en) * | 1971-04-29 | 1972-11-02 | Dr. Karl Thomae Gmbh, 7950 Biberach | Base-substd quinazolines - thrombocyte aggregation inhibitors |
| US3819628A (en) * | 1972-07-31 | 1974-06-25 | Sandoz Ag | 2-phenyl-4-substituted amino-quinazolines and nitrates thereof |
| CH612432A5 (enExample) * | 1975-05-12 | 1979-07-31 | Sandoz Ag | |
| US4306065A (en) * | 1979-12-19 | 1981-12-15 | A. H. Robins Company, Incorporated | 2-Aryl-4-substituted quinazolines |
| US4377582A (en) * | 1979-12-19 | 1983-03-22 | A. H. Robins Company, Inc. | 2-Phenyl-4-[cis-2,5-dimethyl-4-(2-pyridinyl)-1-piperazinyl]quinazoline |
| JPS56120768A (en) * | 1980-01-31 | 1981-09-22 | Ciba Geigy Ag | Color developing quinazoline compound |
| JPS58172379A (ja) * | 1982-04-02 | 1983-10-11 | Showa Denko Kk | 新規なキナゾリン誘導体 |
| EP0655456B1 (en) * | 1993-06-17 | 2000-09-06 | Otsuka Pharmaceutical Factory, Inc. | Phosphonic diester derivative |
| EP0655465B1 (de) * | 1993-11-25 | 1997-07-30 | BASF Aktiengesellschaft | Verfahren zum Beseitigen restflüchtiger Anteile aus Polyacrylatschmelzen |
| JPH083144A (ja) | 1994-06-21 | 1996-01-09 | Chugai Pharmaceut Co Ltd | キナゾリン及びキノリン誘導体 |
| GB2295387A (en) | 1994-11-23 | 1996-05-29 | Glaxo Inc | Quinazoline antagonists of alpha 1c adrenergic receptors |
| FR2751656B1 (fr) * | 1996-07-24 | 1998-10-16 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
| GB9718972D0 (en) * | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| DK0882717T3 (da) | 1996-10-01 | 2010-12-13 | Kyowa Hakko Kirin Co Ltd | Nitrogenholdige heterocykliske forbindelser |
| HUP0000288A3 (en) | 1996-12-13 | 2001-04-28 | Lilly Co Eli | Azetidinone derivatives as inhibitors of the enzymatic activity of psa, intermediates, process for their preparation and pharmaceutical compositions thereof |
| JP3989102B2 (ja) * | 1997-10-02 | 2007-10-10 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 縮合ピリジン誘導体 |
| DE19747063A1 (de) * | 1997-10-24 | 1999-04-29 | Basf Ag | 3-substituierte Tetrahydropyridopyrimidinon-Derivate, ihre Herstellung und Verwendung |
| DE19756388A1 (de) * | 1997-12-18 | 1999-06-24 | Hoechst Marion Roussel De Gmbh | Substituierte 2-Aryl-4-amino-chinazoline |
| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| JP3018185B1 (ja) * | 1999-02-12 | 2000-03-13 | 工業技術院長 | キナゾリン誘導体又はその塩の製造方法 |
| JP2001068452A (ja) * | 1999-08-26 | 2001-03-16 | Matsushita Electric Ind Co Ltd | 回路パターン形成済シリコン基板のエッチング装置およびエッチング方法 |
| JP2001089452A (ja) | 1999-09-22 | 2001-04-03 | Sankyo Co Ltd | ピリミジン誘導体 |
| ES2156574B1 (es) * | 1999-11-18 | 2002-02-01 | Vita Invest Sa | Nuevos derivados de tiazolidindiona como agentes antidiabeticos |
| WO2001083456A1 (en) | 2000-04-27 | 2001-11-08 | Yamanouchi Pharmaceutical Co., Ltd. | Condensed heteroaryl derivatives |
| US6608053B2 (en) * | 2000-04-27 | 2003-08-19 | Yamanouchi Pharmaceutical Co., Ltd. | Fused heteroaryl derivatives |
| CA2418656C (en) | 2000-08-10 | 2011-02-01 | Mitsubishi Pharma Corporation | Proline derivatives and use thereof as drugs |
| CN1474815A (zh) | 2000-09-20 | 2004-02-11 | Ĭ��ר���ɷ�����˾ | 4-氨基-喹唑啉 |
| US20040038856A1 (en) | 2002-05-17 | 2004-02-26 | Sarvajit Chakravarty | Treatment of fibroproliferative disorders using TGF-beta inhibitors |
| AU2003255482A1 (en) | 2002-10-02 | 2004-04-23 | Merck Patent Gmbh | Use of 4 amino-quinazolines as anti cancer agents |
| WO2004081009A1 (en) * | 2003-03-12 | 2004-09-23 | Millennium Pharmaceuticals, Inc. | Quinazoline derivatives as tgf-beta inhibitors |
| TWI289217B (en) * | 2004-07-16 | 2007-11-01 | Hon Hai Prec Ind Co Ltd | Light guide plate |
| US8283354B2 (en) * | 2004-09-02 | 2012-10-09 | Vertex Pharmaceuticals Incorporated | Quinazolines useful as modulators of ion channels |
| US7718658B2 (en) * | 2004-09-02 | 2010-05-18 | Vertex Pharmaceuticals Incorporated | Quinazolines useful as modulators of ion channels |
| US7928107B2 (en) * | 2004-09-02 | 2011-04-19 | Vertex Pharmaceuticals Incorporated | Quinazolines useful as modulators of ion channels |
| RU2007127315A (ru) * | 2004-12-17 | 2009-01-27 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Способы получения 4-аминохиназолинов |
| ATE540033T1 (de) | 2005-11-14 | 2012-01-15 | Vertex Pharma | Als modulatoren von spannungsgesteuerten ionenkanälen geeignete chinazoline |
-
2004
- 2004-03-02 CL CL200400409A patent/CL2004000409A1/es unknown
- 2004-03-03 AR ARP040100670A patent/AR044502A1/es not_active Application Discontinuation
- 2004-03-03 ES ES04716887T patent/ES2338553T3/es not_active Expired - Lifetime
- 2004-03-03 BR BR0408026-2A patent/BRPI0408026A/pt not_active IP Right Cessation
- 2004-03-03 TW TW093105557A patent/TW200426147A/zh unknown
- 2004-03-03 NZ NZ542664A patent/NZ542664A/en unknown
- 2004-03-03 CA CA002517844A patent/CA2517844A1/en not_active Abandoned
- 2004-03-03 JP JP2006509028A patent/JP5247027B2/ja not_active Expired - Fee Related
- 2004-03-03 EP EP04716887A patent/EP1608632B1/en not_active Expired - Lifetime
- 2004-03-03 KR KR1020057016287A patent/KR20050108379A/ko not_active Ceased
- 2004-03-03 AU AU2004217891A patent/AU2004217891B2/en not_active Ceased
- 2004-03-03 US US10/792,688 patent/US7678802B2/en not_active Expired - Lifetime
- 2004-03-03 PE PE2004000236A patent/PE20041059A1/es not_active Application Discontinuation
- 2004-03-03 AT AT04716887T patent/ATE453629T1/de active
- 2004-03-03 DE DE602004024873T patent/DE602004024873D1/de not_active Expired - Lifetime
- 2004-03-03 UY UY28215A patent/UY28215A1/es not_active Application Discontinuation
- 2004-03-03 RU RU2005130486/04A patent/RU2378260C2/ru not_active IP Right Cessation
- 2004-03-03 WO PCT/US2004/006451 patent/WO2004078733A1/en not_active Ceased
-
2005
- 2005-09-04 IL IL170636A patent/IL170636A/en not_active IP Right Cessation
- 2005-10-03 NO NO20054546A patent/NO20054546L/no not_active Application Discontinuation
-
2010
- 2010-01-15 US US12/688,163 patent/US8343980B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US8343980B2 (en) | 2013-01-01 |
| NZ542664A (en) | 2009-03-31 |
| KR20050108379A (ko) | 2005-11-16 |
| ES2338553T3 (es) | 2010-05-10 |
| UY28215A1 (es) | 2004-09-30 |
| HK1088314A1 (en) | 2006-11-03 |
| US20040248890A1 (en) | 2004-12-09 |
| NO20054546L (no) | 2005-11-25 |
| CL2004000409A1 (es) | 2005-01-07 |
| BRPI0408026A (pt) | 2006-02-07 |
| WO2004078733A1 (en) | 2004-09-16 |
| RU2378260C2 (ru) | 2010-01-10 |
| AU2004217891B2 (en) | 2011-06-23 |
| DE602004024873D1 (de) | 2010-02-11 |
| JP5247027B2 (ja) | 2013-07-24 |
| JP2006522119A (ja) | 2006-09-28 |
| AU2004217891A1 (en) | 2004-09-16 |
| EP1608632B1 (en) | 2009-12-30 |
| IL170636A (en) | 2012-08-30 |
| AR044502A1 (es) | 2005-09-14 |
| US20110021495A1 (en) | 2011-01-27 |
| PE20041059A1 (es) | 2005-02-07 |
| CA2517844A1 (en) | 2004-09-16 |
| NO20054546D0 (no) | 2005-10-03 |
| EP1608632A1 (en) | 2005-12-28 |
| ATE453629T1 (de) | 2010-01-15 |
| US7678802B2 (en) | 2010-03-16 |
| RU2005130486A (ru) | 2006-05-10 |
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