NO318884B1 - Pyrazolopyridinderivater som selektive COX-2 inhibitorer, anvendelse og fremgangsmate for fremstillling derav, samt farmasoytisk preparat - Google Patents
Pyrazolopyridinderivater som selektive COX-2 inhibitorer, anvendelse og fremgangsmate for fremstillling derav, samt farmasoytisk preparat Download PDFInfo
- Publication number
- NO318884B1 NO318884B1 NO20012156A NO20012156A NO318884B1 NO 318884 B1 NO318884 B1 NO 318884B1 NO 20012156 A NO20012156 A NO 20012156A NO 20012156 A NO20012156 A NO 20012156A NO 318884 B1 NO318884 B1 NO 318884B1
- Authority
- NO
- Norway
- Prior art keywords
- pyrazolo
- ene
- trifluoromethyl
- pyridin
- phenyl
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 28
- 230000008569 process Effects 0.000 title claims description 11
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A61P27/16—Otologicals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Psychiatry (AREA)
- AIDS & HIV (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9824062.5A GB9824062D0 (en) | 1998-11-03 | 1998-11-03 | Chemical compounds |
GBGB9920909.0A GB9920909D0 (en) | 1999-09-03 | 1999-09-03 | Chemical compounds |
PCT/EP1999/008186 WO2000026216A1 (en) | 1998-11-03 | 1999-11-01 | Pyrazolopyridine derivatives as selective cox-2 inhibitors |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20012156D0 NO20012156D0 (no) | 2001-05-02 |
NO20012156L NO20012156L (no) | 2001-07-02 |
NO318884B1 true NO318884B1 (no) | 2005-05-18 |
Family
ID=26314603
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20012156A NO318884B1 (no) | 1998-11-03 | 2001-05-02 | Pyrazolopyridinderivater som selektive COX-2 inhibitorer, anvendelse og fremgangsmate for fremstillling derav, samt farmasoytisk preparat |
Country Status (24)
Country | Link |
---|---|
US (1) | US7223772B1 (zh) |
EP (1) | EP1127058B1 (zh) |
JP (1) | JP3420751B2 (zh) |
KR (1) | KR20010075673A (zh) |
CN (1) | CN1263755C (zh) |
AR (1) | AR021055A1 (zh) |
AT (1) | ATE275148T1 (zh) |
AU (1) | AU767464B2 (zh) |
BR (1) | BR9915011A (zh) |
CA (1) | CA2349567A1 (zh) |
CO (1) | CO5150164A1 (zh) |
CZ (1) | CZ20011556A3 (zh) |
DE (1) | DE69919887T2 (zh) |
ES (1) | ES2228127T3 (zh) |
GC (1) | GC0000112A (zh) |
HU (1) | HUP0104204A3 (zh) |
MY (1) | MY119689A (zh) |
NO (1) | NO318884B1 (zh) |
NZ (1) | NZ511349A (zh) |
PE (1) | PE20001305A1 (zh) |
PL (1) | PL348208A1 (zh) |
TR (1) | TR200101208T2 (zh) |
TW (1) | TW542836B (zh) |
WO (1) | WO2000026216A1 (zh) |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CO5190664A1 (es) | 1999-06-30 | 2002-08-29 | Pfizer Prod Inc | Terapia de combinacion para el tratamiento de migrana administracion de un receptor 5ht, cafeina y un inhibidor de ciclooxigenasa-2 |
GB0002312D0 (en) * | 2000-02-01 | 2000-03-22 | Glaxo Group Ltd | Medicaments |
PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
ES2243579T3 (es) | 2000-12-15 | 2005-12-01 | Glaxo Group Ltd | Derivados de pirazolopirideno. |
DE60112609T2 (de) | 2000-12-15 | 2006-01-19 | Glaxo Group Ltd., Greenford | Pyrazolopyridine |
ATE274515T1 (de) | 2001-03-08 | 2004-09-15 | Smithkline Beecham Corp | Pyrazolopyridinderivate |
US7034030B2 (en) | 2001-03-30 | 2006-04-25 | Smithkline Beecham Corporation | Pyralopyridines, process for their preparation and use as therapeutic compounds |
WO2002083672A1 (en) | 2001-04-10 | 2002-10-24 | Smithkline Beecham Corporation | Antiviral pyrazolopyridine compounds |
US20030105144A1 (en) | 2001-04-17 | 2003-06-05 | Ping Gao | Stabilized oral pharmaceutical composition |
DE60204452T2 (de) | 2001-04-27 | 2005-12-15 | Smithkline Beecham Corp. | Pyrazolo[1,5a]Pyridinderivate |
EP1401836B1 (en) | 2001-06-21 | 2006-08-23 | SmithKline Beecham Corporation | Imidazo¬1,2-a|pyridine derivatives for the prophylaxis and treatment of herpes viral infections |
JP2005507878A (ja) * | 2001-09-07 | 2005-03-24 | スミスクライン ビーチャム コーポレーション | ヘルペス感染症を治療するためのピラゾロ−ピリジン類 |
DE60211539T2 (de) | 2001-10-05 | 2006-09-21 | Smithkline Beecham Corp. | Imidazopyridinderivate zur verwendung bei der behandlung von herpes-vireninfektion |
GB0124934D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124939D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124933D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124936D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
DE60222465T2 (de) | 2001-12-11 | 2008-06-05 | Smithkline Beecham Corp. | Pyrazolopyridin-derivate als antiherpesmittel |
US7125898B2 (en) | 2002-02-12 | 2006-10-24 | Smithkline Beecham Corporation | Nicotinamide derivatives useful as p38 inhibitors. |
EP1546128B1 (en) | 2002-08-19 | 2006-05-03 | Glaxo Group Limited | Pyrimidine derivatives as selective cox-2 inhibitors |
UY27939A1 (es) | 2002-08-21 | 2004-03-31 | Glaxo Group Ltd | Compuestos |
UA80296C2 (en) * | 2002-09-06 | 2007-09-10 | Biogen Inc | Imidazolopyridines and methods of making and using the same |
WO2004033454A1 (en) | 2002-10-03 | 2004-04-22 | Smithkline Beecham Corporation | Therapeutic compounds based on pyrazolopyridine derivatives |
UA81453C2 (en) | 2003-02-27 | 2008-01-10 | Pyrazolopyridine derivates | |
GB0308185D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
GB0308201D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
GB0308186D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
PL1745791T3 (pl) | 2003-05-07 | 2013-11-29 | Osteologix As | Leczenie chorób chrząstki/kości za pomocą rozpuszczalnych w wodzie soli strontu |
GB0318814D0 (en) | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
AR052429A1 (es) | 2004-12-23 | 2007-03-21 | Glaxo Group Ltd | Compuesto de arilpiridina, composicion farmaceutica que lo comprende, su uso para l a eleboracion de un medicamento y procedimiento para prepararlo |
DE102005024012A1 (de) * | 2005-05-20 | 2006-11-23 | Grünenthal GmbH | Verwendung von 2,5-disubstituierten Thiazol-4-on-Derivaten in Arzneimitteln |
AU2007258567B2 (en) * | 2006-06-06 | 2012-04-19 | Medicinova, Inc. | Substituted pyrazolo (1,5-alpha) pyridine compounds and their methods of use |
JP2010516679A (ja) * | 2007-01-19 | 2010-05-20 | マリンクロット インコーポレイテッド | 診断用および治療用シクロオキシゲナーゼ−2結合リガンド |
GB0704407D0 (en) | 2007-03-07 | 2007-04-18 | Glaxo Group Ltd | Compounds |
US7943658B2 (en) | 2007-07-23 | 2011-05-17 | Bristol-Myers Squibb Company | Indole indane amide compounds useful as CB2 agonists and method |
UA103319C2 (en) * | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
GB0813144D0 (en) | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
GB0813142D0 (en) | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
WO2011012622A1 (en) | 2009-07-30 | 2011-02-03 | Glaxo Group Limited | Benzoxazinone derivatives for the treatment of glytl mediated disorders |
WO2011023753A1 (en) | 2009-08-27 | 2011-03-03 | Glaxo Group Limited | Benzoxazine derivatives as glycine transport inhibitors |
GB201000685D0 (en) | 2010-01-15 | 2010-03-03 | Glaxo Group Ltd | Novel compounds |
GB201007791D0 (en) | 2010-05-10 | 2010-06-23 | Glaxo Group Ltd | Novel compounds |
GB201007789D0 (en) | 2010-05-10 | 2010-06-23 | Glaxo Group Ltd | Novel Compound |
US9115132B2 (en) | 2010-07-09 | 2015-08-25 | Convergence Pharmaceuticals Limited | Tetrazole compounds as calcium channel blockers |
ES2541416T3 (es) | 2011-01-19 | 2015-07-20 | Convergence Pharmaceuticals Limited | Derivados de piperazina como bloqueadores de los canales de calcio Cav2.2 |
GB201122113D0 (en) | 2011-12-22 | 2012-02-01 | Convergence Pharmaceuticals | Novel compounds |
GB201417499D0 (en) | 2014-10-03 | 2014-11-19 | Convergence Pharmaceuticals | Novel use |
GB201417500D0 (en) | 2014-10-03 | 2014-11-19 | Convergence Pharmaceuticals | Novel use |
GB201417497D0 (en) | 2014-10-03 | 2014-11-19 | Convergence Pharmaceuticals | Novel use |
CA3209491A1 (en) | 2021-03-15 | 2022-09-22 | Saul Yedgar | Hyaluronic acid-conjugated dipalmitoyl phosphatidyl ethanolamine in combination with non-steroidal anti-inflammatory drugs (nsaids) for treating or alleviating inflammatory disease |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4925849A (en) | 1987-06-15 | 1990-05-15 | Fujisawa Pharmaceutical Company, Ltd. | Pharmaceutically useful pyrazolopyridines |
US5155114A (en) | 1989-01-23 | 1992-10-13 | Fujisawa Pharmaceutical Company, Ltd. | Method of treatment using pyrazolopyridine compound |
GB8901423D0 (en) | 1989-01-23 | 1989-03-15 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
KR920702621A (ko) | 1989-06-13 | 1992-10-06 | 스튜어트 알. 슈터 | 단핵세포 및/또는 마크로파지에 의한 인터루킨-1 또는 종양회사인자 생성의 억제 |
AU622330B2 (en) | 1989-06-23 | 1992-04-02 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds having a nitrogen atom in the bridgehead for use as fungicides |
WO1991019497A1 (en) | 1990-06-12 | 1991-12-26 | Smithkline Beecham Corporation | Inhibition of 5-lipoxygenase and cyclooxygenase pathway mediated diseases |
GB9015764D0 (en) | 1990-07-18 | 1990-09-05 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
US5300478A (en) | 1993-01-28 | 1994-04-05 | Zeneca Limited | Substituted fused pyrazolo compounds |
US5474995A (en) | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
US5521213A (en) | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
US5552422A (en) | 1995-01-11 | 1996-09-03 | Merck Frosst Canada, Inc. | Aryl substituted 5,5 fused aromatic nitrogen compounds as anti-inflammatory agents |
HUP9801602A3 (en) | 1995-04-04 | 1999-01-28 | Glaxo Group Ltd | Imidazo[1,2-a]pyridine derivatives, process for their production, pharmaceutical compositions and use thereof |
EP0833622B8 (en) | 1995-06-12 | 2005-10-12 | G.D. Searle & Co. | Compositions comprising a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor |
US5700816A (en) | 1995-06-12 | 1997-12-23 | Isakson; Peter C. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor |
US6342510B1 (en) | 1995-06-12 | 2002-01-29 | G. D. Searle & Co. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitors and a leukotriene B4 receptor antagonist |
EP1510519B1 (en) | 1997-09-05 | 2006-02-15 | Glaxo Group Limited | Pharmaceutical compositions comprising 2,3-diarylpyrazolo[1,5-B]pyridazine derivatives |
GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
US6711762B2 (en) | 2002-01-30 | 2004-03-30 | Ktk Services, Inc. | Method of using a truck cab bridge bed |
-
1999
- 1999-11-01 DE DE69919887T patent/DE69919887T2/de not_active Expired - Fee Related
- 1999-11-01 CZ CZ20011556A patent/CZ20011556A3/cs unknown
- 1999-11-01 AR ARP990105525A patent/AR021055A1/es unknown
- 1999-11-01 ES ES99955897T patent/ES2228127T3/es not_active Expired - Lifetime
- 1999-11-01 HU HU0104204A patent/HUP0104204A3/hu unknown
- 1999-11-01 JP JP2000579604A patent/JP3420751B2/ja not_active Expired - Fee Related
- 1999-11-01 NZ NZ511349A patent/NZ511349A/en unknown
- 1999-11-01 CN CNB99815234XA patent/CN1263755C/zh not_active Expired - Fee Related
- 1999-11-01 PL PL99348208A patent/PL348208A1/xx not_active Application Discontinuation
- 1999-11-01 CA CA002349567A patent/CA2349567A1/en not_active Abandoned
- 1999-11-01 US US09/830,836 patent/US7223772B1/en not_active Expired - Fee Related
- 1999-11-01 KR KR1020017005495A patent/KR20010075673A/ko not_active Application Discontinuation
- 1999-11-01 WO PCT/EP1999/008186 patent/WO2000026216A1/en not_active Application Discontinuation
- 1999-11-01 TR TR2001/01208T patent/TR200101208T2/xx unknown
- 1999-11-01 AT AT99955897T patent/ATE275148T1/de not_active IP Right Cessation
- 1999-11-01 AU AU12667/00A patent/AU767464B2/en not_active Ceased
- 1999-11-01 EP EP99955897A patent/EP1127058B1/en not_active Expired - Lifetime
- 1999-11-01 BR BR9915011-5A patent/BR9915011A/pt not_active IP Right Cessation
- 1999-11-02 CO CO99068974A patent/CO5150164A1/es unknown
- 1999-11-02 TW TW088119040A patent/TW542836B/zh not_active IP Right Cessation
- 1999-11-02 GC GCP1999355 patent/GC0000112A/xx active
- 1999-11-02 MY MYPI99004739A patent/MY119689A/en unknown
- 1999-11-03 PE PE1999001103A patent/PE20001305A1/es not_active Application Discontinuation
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2001
- 2001-05-02 NO NO20012156A patent/NO318884B1/no unknown
Also Published As
Publication number | Publication date |
---|---|
TR200101208T2 (tr) | 2001-10-22 |
BR9915011A (pt) | 2001-08-07 |
MY119689A (en) | 2005-06-30 |
HUP0104204A3 (en) | 2002-06-28 |
NO20012156D0 (no) | 2001-05-02 |
PE20001305A1 (es) | 2000-12-06 |
ATE275148T1 (de) | 2004-09-15 |
EP1127058A1 (en) | 2001-08-29 |
DE69919887D1 (de) | 2004-10-07 |
DE69919887T2 (de) | 2005-09-15 |
CN1332741A (zh) | 2002-01-23 |
US7223772B1 (en) | 2007-05-29 |
PL348208A1 (en) | 2002-05-06 |
CA2349567A1 (en) | 2000-05-11 |
ES2228127T3 (es) | 2005-04-01 |
CN1263755C (zh) | 2006-07-12 |
JP3420751B2 (ja) | 2003-06-30 |
CO5150164A1 (es) | 2002-04-29 |
WO2000026216A1 (en) | 2000-05-11 |
AR021055A1 (es) | 2002-06-12 |
NZ511349A (en) | 2003-10-31 |
EP1127058B1 (en) | 2004-09-01 |
NO20012156L (no) | 2001-07-02 |
HUP0104204A2 (hu) | 2002-04-29 |
KR20010075673A (ko) | 2001-08-09 |
AU767464B2 (en) | 2003-11-13 |
GC0000112A (en) | 2005-06-29 |
TW542836B (en) | 2003-07-21 |
JP2002528547A (ja) | 2002-09-03 |
AU1266700A (en) | 2000-05-22 |
CZ20011556A3 (cs) | 2001-11-14 |
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