ES2136037A1 - Inhibidores de sulfamida-metaloproteasa - Google Patents

Inhibidores de sulfamida-metaloproteasa

Info

Publication number
ES2136037A1
ES2136037A1 ES009800113A ES9800113A ES2136037A1 ES 2136037 A1 ES2136037 A1 ES 2136037A1 ES 009800113 A ES009800113 A ES 009800113A ES 9800113 A ES9800113 A ES 9800113A ES 2136037 A1 ES2136037 A1 ES 2136037A1
Authority
ES
Spain
Prior art keywords
sulfamide
metalloprotease inhibitors
inhibitors
methods
metalloprotease
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
ES009800113A
Other languages
English (en)
Other versions
ES2136037B1 (es
Inventor
Chris Allen Broka
Jeffrey Allen Cambell
Arlindo Lucas Castelhando
Jian Jeffrey Chen
Robert Than Hendricks
Michael Joseph Melnick
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
F Hoffmann La Roche AG
Agouron Pharmaceuticals LLC
Original Assignee
F Hoffmann La Roche AG
Agouron Pharmaceuticals LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26713422&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2136037(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by F Hoffmann La Roche AG, Agouron Pharmaceuticals LLC filed Critical F Hoffmann La Roche AG
Publication of ES2136037A1 publication Critical patent/ES2136037A1/es
Application granted granted Critical
Publication of ES2136037B1 publication Critical patent/ES2136037B1/es
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • C07D295/26—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C307/04—Diamides of sulfuric acids
    • C07C307/06—Diamides of sulfuric acids having nitrogen atoms of the sulfamide groups bound to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Detergent Compositions (AREA)

Abstract

Inhibidores de sulfamida-metaloproteasa. Están constituidos por sulfamidas de fórmula (I), en donde R1, R2, R3, R10, R20, R21, están definidos en la memoria y en las reivindicaciones. Estos productos son inhibidores de metaloproteasas. La invención se refiere también a composiciones farmacéuticas que contienen a estos productos, métodos para su empleo, y métodos para la preparación de los compuestos. Los productos de la invención se usan para el tratamiento de mamíferos que tengan estadios de enfermedad que se alivian mediante la inhibición de las mencionadas metaloproteasas.
ES009800113A 1997-01-23 1998-01-22 Inhibidores de sulfamida-metaloproteasa Expired - Fee Related ES2136037B1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3671497P 1997-01-23 1997-01-23
US6220997P 1997-10-16 1997-10-16

Publications (2)

Publication Number Publication Date
ES2136037A1 true ES2136037A1 (es) 1999-11-01
ES2136037B1 ES2136037B1 (es) 2000-11-16

Family

ID=26713422

Family Applications (2)

Application Number Title Priority Date Filing Date
ES98907943T Expired - Lifetime ES2183331T3 (es) 1997-01-23 1998-01-14 Inhibidores de sulfamida-metaloproteasa.
ES009800113A Expired - Fee Related ES2136037B1 (es) 1997-01-23 1998-01-22 Inhibidores de sulfamida-metaloproteasa

Family Applications Before (1)

Application Number Title Priority Date Filing Date
ES98907943T Expired - Lifetime ES2183331T3 (es) 1997-01-23 1998-01-14 Inhibidores de sulfamida-metaloproteasa.

Country Status (35)

Country Link
EP (1) EP0958287B2 (es)
JP (1) JP3563411B2 (es)
KR (1) KR100377696B1 (es)
CN (1) CN1093125C (es)
AR (1) AR011425A1 (es)
AT (1) ATE223909T1 (es)
AU (1) AU730127B2 (es)
BG (1) BG103586A (es)
BR (1) BR9807508A (es)
CA (1) CA2278694C (es)
DE (2) DE69807845T2 (es)
DK (1) DK0958287T3 (es)
EA (1) EA002810B1 (es)
ES (2) ES2183331T3 (es)
FR (1) FR2758559A1 (es)
GB (1) GB2321641B (es)
HR (1) HRP980036A2 (es)
HU (1) HUP0000941A3 (es)
ID (1) ID22849A (es)
IL (1) IL130802A0 (es)
IS (1) IS5125A (es)
IT (1) IT1298163B1 (es)
MA (1) MA26467A1 (es)
NO (1) NO313635B1 (es)
NZ (1) NZ336625A (es)
OA (1) OA11078A (es)
PA (1) PA8445301A1 (es)
PE (1) PE57399A1 (es)
PL (1) PL334846A1 (es)
PT (1) PT958287E (es)
TN (1) TNSN98012A1 (es)
TR (1) TR199901765T2 (es)
UY (1) UY24854A1 (es)
WO (1) WO1998032748A1 (es)
YU (1) YU34599A (es)

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JP2003501414A (ja) * 1999-06-04 2003-01-14 アストラゼネカ・アクチエボラーグ メタロプロテイナーゼの阻害剤
DE60008548T2 (de) 1999-08-18 2004-08-05 Warner-Lambert Co. Llc Hydroxamsäurederivate als matrix-metalloproteinase-inhibitoren
GT200000203A (es) 1999-12-01 2002-05-24 Compuestos, composiciones y metodos para estimular el crecimiento y elongacion de neuronas.
AU2001232113A1 (en) * 2000-02-21 2001-09-03 Astrazeneca Ab Arylpiperazines and their use as metalloproteinase inhibiting agents (mmp)
UA73155C2 (en) * 2000-02-21 2005-06-15 Astrazeneca Ab Substituted by piperidine and piperazine n-hydroxyformamides as metalloproteinase inhibitors
US6495358B1 (en) * 2000-04-19 2002-12-17 Wichita State University Sulfamide and bis-sulfamide amino acid derivatives as inhibitors of proteolytic enzymes
US6897237B2 (en) 2000-04-28 2005-05-24 Shionogi & Co. Ltd. MMP-12 inhibitors
US6492171B2 (en) 2000-05-16 2002-12-10 Isis Pharmaceuticals, Inc. Antisense modulation of TERT expression
US6331399B1 (en) 2000-05-16 2001-12-18 Isis Pharmaceuticals, Inc. Antisense inhibition of tert expression
GB0119474D0 (en) 2001-08-09 2001-10-03 Astrazeneca Ab Compounds
JP4219810B2 (ja) * 2001-10-26 2009-02-04 塩野義製薬株式会社 Ｍｍｐ阻害作用を有するスルホンアミド誘導体
NZ536116A (en) * 2002-04-03 2007-01-26 Topotarget Uk Ltd Carbamic acid compounds comprising a piperazine linkage as HDAC inhibitors
MY140680A (en) 2002-05-20 2010-01-15 Bristol Myers Squibb Co Hepatitis c virus inhibitors
WO2003106381A2 (en) 2002-06-12 2003-12-24 Exelixis, Inc. Human adam-10 inhibitors
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DE10344936A1 (de) * 2003-09-27 2005-04-21 Aventis Pharma Gmbh Bicyclische Iminosäurederivate als Inhibitoren von Matrix-Metalloproteinasen
CN1997370B (zh) 2004-05-19 2011-06-01 索尔瓦药物有限公司 N-氨磺酰-n＇-芳基哌嗪类化合物在制备用于预防或治疗肥胖和相关疾病的药物中的用途
TW200626138A (en) * 2004-09-20 2006-08-01 Xenon Pharmaceuticals Inc Heterocyclic derivatives and their use as therapeutic agents
DE102004060229A1 (de) 2004-12-15 2006-06-29 Sanofi-Aventis Deutschland Gmbh Neue zyklische Harnstoffe als Inhibitoren von Metallproteasen
US20090069304A1 (en) 2006-03-03 2009-03-12 Shionogi & Co., Ltd. Mmp-13 selective inhibitor
WO2008053913A1 (fr) 2006-11-02 2008-05-08 Shionogi & Co., Ltd. Dérivé de sulfonylurée capable d'inhiber sélectivement mmp-13
WO2008147764A1 (en) * 2007-05-23 2008-12-04 Array Biopharma, Inc. Mmp inhibitors and methods of use thereof
JP5465672B2 (ja) * 2007-10-12 2014-04-09 ビーエーエスエフ ソシエタス・ヨーロピア スルホン酸ジアミドの製法
FR2947268B1 (fr) 2009-06-30 2011-08-26 Galderma Res & Dev Nouveaux composes benzene-sulfonamides, leur procede de synthese et leur utilisation en medecine ainsi qu'en cosmetique
EP2456757B1 (en) * 2009-07-22 2019-05-01 The Board of Trustees of the University of Illionis Hdac inhibitors and therapeutic methods using the same
JP6463631B2 (ja) * 2011-06-09 2019-02-06 ライゼン・ファーマシューティカルズ・エスアー Ｇｐｒ−１１９のモジュレータとしての新規化合物
PT3297992T (pt) * 2015-05-22 2020-03-17 Chong Kun Dang Pharmaceutical Corp Compostos derivados de alquilo heterocíclicos como inibidores seletivos da histona desacetilase e composições farmacêuticas que compreendem os mesmos
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Also Published As

Publication number Publication date
EA002810B1 (ru) 2002-10-31
EP0958287B1 (en) 2002-09-11
NO993587L (no) 1999-09-22
TNSN98012A1 (fr) 2005-03-15
JP3563411B2 (ja) 2004-09-08
AR011425A1 (es) 2000-08-16
HUP0000941A3 (en) 2002-06-28
NO993587D0 (no) 1999-07-22
MA26467A1 (fr) 2004-12-20
ATE223909T1 (de) 2002-09-15
OA11078A (en) 2003-03-17
HRP980036A2 (en) 1998-12-31
NZ336625A (en) 2001-04-27
EA199900643A1 (ru) 2000-04-24
PE57399A1 (es) 1999-06-25
CA2278694C (en) 2006-09-26
EP0958287B2 (en) 2008-04-09
BG103586A (bg) 2000-03-31
ES2136037B1 (es) 2000-11-16
DE69807845D1 (de) 2002-10-17
FR2758559A1 (fr) 1998-07-24
GB2321641B (en) 2001-04-04
KR20000070398A (ko) 2000-11-25
NO313635B1 (no) 2002-11-04
DE69807845T2 (de) 2003-06-05
IS5125A (is) 1999-07-22
DE19802350A1 (de) 1998-07-30
WO1998032748A1 (en) 1998-07-30
PT958287E (pt) 2002-12-31
JP2001523222A (ja) 2001-11-20
DK0958287T3 (da) 2003-01-20
AU730127B2 (en) 2001-02-22
ID22849A (id) 1999-12-09
IT1298163B1 (it) 1999-12-20
AU6614098A (en) 1998-08-18
CA2278694A1 (en) 1998-07-30
ITMI980091A1 (it) 1999-07-20
BR9807508A (pt) 2000-03-21
PA8445301A1 (es) 2001-07-31
PL334846A1 (en) 2000-03-27
IL130802A0 (en) 2001-01-28
EP0958287A1 (en) 1999-11-24
HUP0000941A2 (hu) 2001-04-28
CN1250445A (zh) 2000-04-12
GB9801393D0 (en) 1998-03-18
GB2321641A (en) 1998-08-05
YU34599A (sh) 2002-03-18
CN1093125C (zh) 2002-10-23
ES2183331T3 (es) 2003-03-16
TR199901765T2 (xx) 1999-10-21
KR100377696B1 (ko) 2003-03-29
UY24854A1 (es) 2000-12-29

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