ZA200300525B - Piperazine derivatives. - Google Patents
Piperazine derivatives. Download PDFInfo
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- ZA200300525B ZA200300525B ZA200300525A ZA200300525A ZA200300525B ZA 200300525 B ZA200300525 B ZA 200300525B ZA 200300525 A ZA200300525 A ZA 200300525A ZA 200300525 A ZA200300525 A ZA 200300525A ZA 200300525 B ZA200300525 B ZA 200300525B
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- ZA
- South Africa
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- compound
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- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 3
- 150000004885 piperazines Chemical class 0.000 title description 2
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- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00116517 | 2000-07-31 |
Publications (1)
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| ZA200300525B true ZA200300525B (en) | 2004-04-20 |
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Country Status (20)
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| AT (1) | ATE305933T1 (enExample) |
| AU (2) | AU8395501A (enExample) |
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| CA (1) | CA2417106C (enExample) |
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| MX (1) | MXPA03000906A (enExample) |
| PA (1) | PA8523601A1 (enExample) |
| PE (1) | PE20020366A1 (enExample) |
| UY (1) | UY26863A1 (enExample) |
| WO (1) | WO2002010169A1 (enExample) |
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| EP1325008B1 (en) * | 2000-07-31 | 2005-10-05 | F. Hoffmann-La Roche Ag | Piperazine derivatives |
| GB0106177D0 (en) | 2001-03-13 | 2001-05-02 | Hoffmann La Roche | Piperazine derivatives |
| US7566728B2 (en) | 2002-03-29 | 2009-07-28 | Mitsubishi Tanabe Pharma Corporation | Remedy for sleep disturbance |
| AU2003243089B2 (en) | 2002-06-19 | 2010-01-07 | Biovitrum Ab (Publ) | Novel compounds, their use and preparation |
| US7105526B2 (en) | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| DE10319612A1 (de) | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| DE10320780A1 (de) * | 2003-05-09 | 2005-01-20 | Bayer Healthcare Ag | Heterocyclyl-substituierte Dihydrochinazoline |
| GB0314967D0 (en) * | 2003-06-26 | 2003-07-30 | Hoffmann La Roche | Piperazine derivatives |
| US20050032930A1 (en) * | 2003-07-02 | 2005-02-10 | Christian Jackson | Inkjet ink |
| US7547693B2 (en) | 2003-09-22 | 2009-06-16 | Banyu Pharmaceutical Co. Ltd. | Piperidine derivative |
| DE10352499A1 (de) * | 2003-11-11 | 2005-06-09 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline II |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| DE102004022672A1 (de) * | 2004-05-07 | 2005-11-24 | Bayer Healthcare Ag | Substituierte Azachinazoline |
| EP1792629A4 (en) | 2004-08-25 | 2010-08-25 | Takeda Pharmaceutical | MEANS FOR THE PREVENTION / TREATMENT OF STRESS-RELATED HARNINE INCONTINENCE AND PRECAUTIONARY METHOD FOR THIS |
| ES2325773T5 (es) | 2004-11-01 | 2014-02-24 | Amylin Pharmaceuticals, Llc. | Tratamiento de la obesidad y de los trastornos relacionados |
| EP2314688B1 (en) | 2004-11-12 | 2014-07-16 | Asuragen, Inc. | Methods and compositions involving miRNA and miRNA inhibitor molecules |
| US7790712B2 (en) | 2005-03-17 | 2010-09-07 | Boehringer Ingelheim Pharmaceutical, Inc. | Substituted [1,4]diazepino[1,2-A]indoles and azepino[1,2-A]indoles as anti-cytokine inhibitors |
| EP1888585B1 (en) * | 2005-05-03 | 2011-06-29 | F. Hoffmann-La Roche AG | Tetracyclic azapyrazinoindolines as 5-ht2 ligands |
| US7737155B2 (en) | 2005-05-17 | 2010-06-15 | Schering Corporation | Nitrogen-containing heterocyclic compounds and methods of use thereof |
| EP1892241B1 (en) | 2005-05-30 | 2016-03-30 | Msd K.K. | Novel piperidine derivative |
| DE102005027517A1 (de) | 2005-06-15 | 2006-12-21 | Bayer Healthcare Ag | Verfahren zur Herstellung von Dihydrochinazolinen |
| EP1916239A4 (en) | 2005-08-10 | 2009-10-21 | Banyu Pharma Co Ltd | PYRIDOLVERBINDUNG |
| EP2330124B1 (en) | 2005-08-11 | 2015-02-25 | Amylin Pharmaceuticals, LLC | Hybrid polypeptides with selectable properties |
| EP2330125A3 (en) | 2005-08-11 | 2012-12-12 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
| JPWO2007024004A1 (ja) | 2005-08-24 | 2009-03-05 | 萬有製薬株式会社 | フェニルピリドン誘導体 |
| EP1939194A4 (en) | 2005-09-07 | 2010-12-08 | Banyu Pharma Co Ltd | BICYCLIC AROMATIC SUBSTITUTED PYRIDONE DERIVATIVE |
| KR20080048502A (ko) | 2005-09-29 | 2008-06-02 | 머크 앤드 캄파니 인코포레이티드 | 멜라노코르틴-4 수용체 조절제로서의 아실화스피로피페리딘 유도체 |
| EP1954257A4 (en) * | 2005-10-14 | 2009-05-20 | Lundbeck & Co As H | METHOD FOR TREATING DISORDERS OF THE CENTRAL NERVOUS SYSTEM WITH A LOW-DOSED COMBINATION OF ESCITALOPRAM AND BUPROPION |
| AU2006304836A1 (en) | 2005-10-21 | 2007-04-26 | Novartis Ag | Combination of a renin-inhibitor and an anti-dyslipidemic agent and/or an antiobesity agent |
| JPWO2007049798A1 (ja) | 2005-10-27 | 2009-04-30 | 萬有製薬株式会社 | 新規ベンゾオキサチイン誘導体 |
| NZ568292A (en) | 2005-11-10 | 2011-08-26 | Msd Kk | Spiro[cyclohexane-1,1'-(3'H)-4'-azaisobenzofuran]-4-carboxamide derivatives |
| CN101321761A (zh) | 2005-12-09 | 2008-12-10 | 霍夫曼-拉罗奇有限公司 | 用于治疗肥胖病的三环酰胺衍生物 |
| UA95788C2 (en) | 2005-12-15 | 2011-09-12 | Ф. Хоффманн-Ля Рош Аг | Fused pyrrole derivatives |
| JP5528699B2 (ja) | 2006-05-16 | 2014-06-25 | 武田薬品工業株式会社 | 縮合複素環化合物およびその用途 |
| AU2007300627B2 (en) | 2006-09-22 | 2012-02-16 | Merck Sharp & Dohme Corp. | Method of treatment using fatty acid synthesis inhibitors |
| EP2072519A4 (en) | 2006-09-28 | 2009-10-21 | Banyu Pharma Co Ltd | DIARYLKETIMINDERIVAT |
| BRPI0806774A2 (pt) | 2007-01-16 | 2011-09-13 | Ipintl Llc | composição para tratamento de sìndrome metabólica |
| FR2912145B1 (fr) * | 2007-02-02 | 2009-03-06 | Servier Lab | Nouveaux derives tricycliques,leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JP5319518B2 (ja) | 2007-04-02 | 2013-10-16 | Ｍｓｄ株式会社 | インドールジオン誘導体 |
| JP5496877B2 (ja) | 2007-04-16 | 2014-05-21 | アッヴィ・インコーポレイテッド | ７−置換インドールＭｃｌ−１阻害薬 |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| JP5546451B2 (ja) | 2007-06-04 | 2014-07-09 | シナジー ファーマシューティカルズ インコーポレイテッド | 胃腸の障害、炎症、癌および他の障害の処置に有用なグアニル酸シクラーゼのアゴニスト |
| US20100120694A1 (en) | 2008-06-04 | 2010-05-13 | Synergy Pharmaceuticals, Inc. | Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders |
| WO2009063992A1 (ja) | 2007-11-15 | 2009-05-22 | Takeda Pharmaceutical Company Limited | 縮合ピリジン誘導体およびその用途 |
| AU2009220605A1 (en) | 2008-03-06 | 2009-09-11 | Msd K.K. | Alkylaminopyridine derivative |
| CN101981025A (zh) | 2008-03-28 | 2011-02-23 | 万有制药株式会社 | 具有黑色素浓缩激素受体拮抗作用的二芳基甲基酰胺衍生物 |
| JP5767101B2 (ja) | 2008-03-28 | 2015-08-19 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | キナーゼ阻害剤として活性な３，４−ジヒドロ−２ｈ−ピラジノ［１，２−ａ］インドール−１−オン誘導体、これらの調製方法、およびこれらを含む医薬組成物 |
| US8440739B2 (en) * | 2008-04-28 | 2013-05-14 | Kuraray Noritake Dental Inc. | Dental composition and composite resin |
| CA2666036C (en) | 2008-05-16 | 2017-09-12 | Chien-Hung Chen | Novel compositions and methods for treating hyperproliferative diseases |
| AU2009261248A1 (en) | 2008-06-19 | 2009-12-23 | Banyu Pharmaceutical Co., Ltd. | Spirodiamine-diarylketoxime derivative |
| EP3241839B1 (en) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| US20110124674A1 (en) | 2008-07-30 | 2011-05-26 | Hiroyuki Kishino | 5/5-or 5/6-membered condensed ring cycloalkylamine derivative |
| EP2348857B1 (en) | 2008-10-22 | 2016-02-24 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| EP2350010B1 (en) | 2008-10-30 | 2014-03-26 | Merck Sharp & Dohme Corp. | Isonicotinamide orexin receptor antagonists |
| AU2009309037A1 (en) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| US20110243940A1 (en) | 2008-12-16 | 2011-10-06 | Schering Corporation | Bicyclic pyranone derivatives and methods of use thereof |
| US20110245209A1 (en) | 2008-12-16 | 2011-10-06 | Schering Corporation | Pyridopyrimidine derivatives and methods of use thereof |
| FI122466B (fi) * | 2009-08-21 | 2012-01-31 | Hollming Oy | Menetelmä työstettävän metallikappaleen kuumentamiseksi ja induktiokuumennustyökalu |
| EP2510949A4 (en) | 2009-12-11 | 2013-11-13 | Astellas Pharma Inc | THERAPEUTICS FOR FIBROMYALGIA |
| US8895596B2 (en) | 2010-02-25 | 2014-11-25 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| MY159058A (en) | 2011-02-25 | 2016-12-15 | Merck Sharp & Dohme | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agent |
| CN108676076A (zh) | 2011-03-01 | 2018-10-19 | 辛纳吉制药公司 | 制备鸟苷酸环化酶c激动剂的方法 |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| LT2825542T (lt) | 2012-03-16 | 2016-12-27 | Vitae Pharmaceuticals, Inc. | Kepenų x receptoriaus moduliatoriai |
| AU2013232066B2 (en) | 2012-03-16 | 2017-07-06 | Vitae Pharmaceuticals, Inc. | Liver X receptor modulators |
| TWI579274B (zh) * | 2012-04-20 | 2017-04-21 | 龍馬躍公司 | 製備１－芳基－５－烷基吡唑化合物的改良方法 |
| EP2880028B1 (en) | 2012-08-02 | 2020-09-30 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| WO2014139388A1 (en) | 2013-03-14 | 2014-09-18 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| AU2014235209B2 (en) | 2013-03-15 | 2018-06-14 | Bausch Health Ireland Limited | Guanylate cyclase receptor agonists combined with other drugs |
| HK1220696A1 (zh) | 2013-03-15 | 2017-05-12 | Bausch Health Ireland Limited | 鸟苷酸环化酶激动剂及其用途 |
| MA38569A1 (fr) * | 2013-04-23 | 2017-03-31 | Esteve Labor Dr | Composés pyrazino[1,2-a]indole, leur préparation et utilisation dans des médicaments |
| EP2989105B1 (en) | 2013-04-23 | 2020-03-11 | Esteve Pharmaceuticals, S.A. | Pyrazino[1,2-a]indole compounds, their preparation and use in medicaments |
| EP4424697A3 (en) | 2013-06-05 | 2024-12-25 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| EP3636649B1 (en) | 2014-01-24 | 2024-02-14 | Turning Point Therapeutics, Inc. | Diaryl macrocycles as modulators of protein kinases |
| BR112017003745A2 (pt) | 2014-08-29 | 2017-12-05 | Tes Pharma S R L | inibidores de semialdeído descarboxilase de ácido alfa-amino-beta-carboximucônico |
| MX389753B (es) | 2015-06-17 | 2025-03-20 | Pfizer | Compuestos triciclicos y su uso como inhibidores de la fosfodiesterasa |
| RU2732405C2 (ru) | 2015-07-02 | 2020-09-16 | Тёрнинг Поинт Терапьютикс, Инк. | Хиральные диарильные макроциклы в качестве модуляторов протеинкиназ |
| WO2017007759A1 (en) | 2015-07-06 | 2017-01-12 | Tp Therapeutics, Inc. | Diaryl macrocycle polymorph |
| TWI767945B (zh) | 2016-10-14 | 2022-06-21 | 義大利商Ｔｅｓ製藥（股份）責任有限公司 | α-胺基-β-羧基己二烯二酸半醛去羧酶之抑制劑 |
| EP3733204A4 (en) | 2017-12-27 | 2021-09-15 | Takeda Pharmaceutical Company Limited | THERAPEUTIC AGENT FOR URINARY INCONTINENCE OF STRESS AND FECAL INCONTINENCE |
| CN113302189B (zh) | 2018-11-20 | 2025-09-05 | Tes制药有限责任公司 | α-氨基-β-羧基己二烯二酸半醛去羧酶的抑制剂 |
| EP3923933A4 (en) | 2019-02-13 | 2022-08-17 | Merck Sharp & Dohme Corp. | PYRROLIDINOREXINE RECEPTOR AGONISTS |
| US11098029B2 (en) | 2019-02-13 | 2021-08-24 | Merck Sharp & Dohme Corp. | 5-alkyl pyrrolidine orexin receptor agonists |
| EP4010314B1 (en) | 2019-08-08 | 2024-02-28 | Merck Sharp & Dohme LLC | Heteroaryl pyrrolidine and piperidine orexin receptor agonists |
| CN116249697A (zh) | 2020-08-18 | 2023-06-09 | 默沙东有限责任公司 | 二环庚烷吡咯烷食欲素受体激动剂 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US652018A (en) * | 1900-02-15 | 1900-06-19 | John C Duner | Gate. |
| US3317524A (en) | 1965-02-04 | 1967-05-02 | American Home Prod | Substituted 1, 2, 3, 4-tetrahydro-pyrazino[1, 2-a]indoles |
| DE2162422A1 (de) | 1971-12-16 | 1973-06-20 | Merck Patent Gmbh | Pyrazinoindol-derivate und verfahren zu ihrer herstellung |
| EP0572863A1 (de) * | 1992-06-05 | 1993-12-08 | F. Hoffmann-La Roche Ag | ZNS Pyrazinoindole |
| US5622950A (en) | 1993-03-01 | 1997-04-22 | Merck, Sharp & Dohme Ltd. | Pyrrolo-pyridine derivatives |
| BR9406128A (pt) | 1993-03-01 | 1996-02-27 | Merck Sharp & Dohme | Uso de um composto processo para o tratamento e/ou prevençao de distúrbios psicóticos composto composiçao farmacêutica processos para a preparaçao de um composto e de uma composiçao farmacêutica |
| US5576319A (en) | 1993-03-01 | 1996-11-19 | Merck, Sharp & Dohme Ltd. | Pyrrolo-pyridine derivatives |
| US6169086B1 (en) | 1997-01-27 | 2001-01-02 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| JP2000169475A (ja) | 1998-07-24 | 2000-06-20 | Dai Ichi Seiyaku Co Ltd | ピラゾ―ル誘導体およびその塩 |
| IL143323A0 (en) * | 1998-12-17 | 2002-04-21 | American Home Prod | 2,3,4,4a-tetrahydro-1h-pyrazino (1,2-a) quinoxalin-5 (6h) one derivatives being 5ht2c agonists |
| GB9902047D0 (en) * | 1999-01-29 | 1999-03-17 | Cerebrus Ltd | Chemical compounds XI |
| EP1325008B1 (en) * | 2000-07-31 | 2005-10-05 | F. Hoffmann-La Roche Ag | Piperazine derivatives |
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2001
- 2001-07-24 EP EP01962869A patent/EP1325008B1/en not_active Expired - Lifetime
- 2001-07-24 BR BR0112918-0A patent/BR0112918A/pt not_active IP Right Cessation
- 2001-07-24 CA CA002417106A patent/CA2417106C/en not_active Expired - Fee Related
- 2001-07-24 ES ES01962869T patent/ES2250459T3/es not_active Expired - Lifetime
- 2001-07-24 KR KR10-2003-7001439A patent/KR100539139B1/ko not_active Expired - Fee Related
- 2001-07-24 DE DE60113865T patent/DE60113865T2/de not_active Expired - Fee Related
- 2001-07-24 DK DK01962869T patent/DK1325008T3/da active
- 2001-07-24 AU AU8395501A patent/AU8395501A/xx active Pending
- 2001-07-24 JP JP2002515898A patent/JP4180365B2/ja not_active Expired - Fee Related
- 2001-07-24 WO PCT/EP2001/008520 patent/WO2002010169A1/en not_active Ceased
- 2001-07-24 MX MXPA03000906A patent/MXPA03000906A/es active IP Right Grant
- 2001-07-24 CN CNB018152260A patent/CN1277828C/zh not_active Expired - Fee Related
- 2001-07-24 AU AU2001283955A patent/AU2001283955B2/en not_active Ceased
- 2001-07-24 AT AT01962869T patent/ATE305933T1/de not_active IP Right Cessation
- 2001-07-25 US US09/912,949 patent/US20020035110A1/en not_active Abandoned
- 2001-07-25 PE PE2001000749A patent/PE20020366A1/es not_active Application Discontinuation
- 2001-07-27 AR ARP010103589A patent/AR030306A1/es unknown
- 2001-07-30 GT GT200100155A patent/GT200100155A/es unknown
- 2001-07-30 UY UY26863A patent/UY26863A1/es not_active Application Discontinuation
- 2001-07-30 PA PA20018523601A patent/PA8523601A1/es unknown
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2003
- 2003-01-20 ZA ZA200300525A patent/ZA200300525B/en unknown
- 2003-03-25 US US10/396,242 patent/US6933387B2/en not_active Expired - Fee Related
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2005
- 2005-06-28 US US11/169,079 patent/US7253281B2/en not_active Expired - Fee Related
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|---|---|
| CN1277828C (zh) | 2006-10-04 |
| KR20030020954A (ko) | 2003-03-10 |
| GT200100155A (es) | 2002-05-16 |
| DK1325008T3 (da) | 2006-02-13 |
| CN1452622A (zh) | 2003-10-29 |
| PA8523601A1 (es) | 2002-10-24 |
| BR0112918A (pt) | 2003-07-01 |
| UY26863A1 (es) | 2002-01-31 |
| US6933387B2 (en) | 2005-08-23 |
| US7253281B2 (en) | 2007-08-07 |
| JP2004505085A (ja) | 2004-02-19 |
| AR030306A1 (es) | 2003-08-20 |
| US20020035110A1 (en) | 2002-03-21 |
| ES2250459T3 (es) | 2006-04-16 |
| JP4180365B2 (ja) | 2008-11-12 |
| WO2002010169A1 (en) | 2002-02-07 |
| CA2417106A1 (en) | 2002-02-07 |
| PE20020366A1 (es) | 2002-05-17 |
| EP1325008B1 (en) | 2005-10-05 |
| KR100539139B1 (ko) | 2005-12-26 |
| CA2417106C (en) | 2007-09-18 |
| US20050239789A1 (en) | 2005-10-27 |
| EP1325008A1 (en) | 2003-07-09 |
| US20070106076A1 (en) | 2007-05-10 |
| DE60113865T2 (de) | 2006-07-20 |
| AU2001283955B2 (en) | 2006-05-18 |
| ATE305933T1 (de) | 2005-10-15 |
| DE60113865D1 (de) | 2006-02-16 |
| MXPA03000906A (es) | 2005-02-24 |
| AU8395501A (en) | 2002-02-13 |
| US20030216401A1 (en) | 2003-11-20 |
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