ES2158689T3 - Analogos de nucleosidos, tales como antivirales, que incluyen inhibidores de transcriptasa inversa retroviral y la adn-polimerasa del virus de la hepatitis b (vhb). - Google Patents

Analogos de nucleosidos, tales como antivirales, que incluyen inhibidores de transcriptasa inversa retroviral y la adn-polimerasa del virus de la hepatitis b (vhb).

Info

Publication number
ES2158689T3
ES2158689T3 ES98939041T ES98939041T ES2158689T3 ES 2158689 T3 ES2158689 T3 ES 2158689T3 ES 98939041 T ES98939041 T ES 98939041T ES 98939041 T ES98939041 T ES 98939041T ES 2158689 T3 ES2158689 T3 ES 2158689T3
Authority
ES
Spain
Prior art keywords
sub
nucleosids
antivirals
hbv
hepatitis
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.)
Expired - Lifetime
Application number
ES98939041T
Other languages
English (en)
Inventor
Xiao-Xiong Zhou
Nils-Gunnar Johansson
Horst Wahling
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.)
Medivir AB
Original Assignee
Medivir AB
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
Priority claimed from SE9702957A external-priority patent/SE9702957D0/xx
Priority claimed from SE9704147A external-priority patent/SE9704147D0/xx
Priority claimed from SE9800452A external-priority patent/SE9800452D0/xx
Application filed by Medivir AB filed Critical Medivir AB
Application granted granted Critical
Publication of ES2158689T3 publication Critical patent/ES2158689T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • 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
    • 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
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • 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
    • 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
    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • C07D213/85—Nitriles in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings 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
    • C07D307/20—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
    • C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Virology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pulmonology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La invención se refiere a un compuesto de la fórmula (I) en el que: nuc es un residuo de un nucleósido análogo unido a través de su simple grupo hidroxi sobre elemento sacárido cíclico o acíclico, R{sub,1} es hidroxi, amino o carboxilo; que opcionalmente puede tener ahí un enlace esterificado/amida; un ácido graso o alcohol C{sub,4}-C{sub,22} opcionalmente sustituido, saturado o insaturado, o un ácido L-amino alifático; R{sub,2} es el residuo de un L-aminoácido alifático; L{sub,1} es un grupo de unión trifuncional; L{sub,2} no existe o es un grupo de unión difuncional; y las sales farmacéuticamente aceptables de éstos que tienen propiedades farmacológicas favorables y son antiviralmente activos.
ES98939041T 1997-08-15 1998-08-14 Analogos de nucleosidos, tales como antivirales, que incluyen inhibidores de transcriptasa inversa retroviral y la adn-polimerasa del virus de la hepatitis b (vhb). Expired - Lifetime ES2158689T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SE9702957A SE9702957D0 (sv) 1997-08-15 1997-08-15 Antivirals
SE9704147A SE9704147D0 (sv) 1997-11-12 1997-11-12 Nucleosides
SE9800452A SE9800452D0 (sv) 1998-02-13 1998-02-13 Antivirals

Publications (1)

Publication Number Publication Date
ES2158689T3 true ES2158689T3 (es) 2001-09-01

Family

ID=27355886

Family Applications (2)

Application Number Title Priority Date Filing Date
ES98939041T Expired - Lifetime ES2158689T3 (es) 1997-08-15 1998-08-14 Analogos de nucleosidos, tales como antivirales, que incluyen inhibidores de transcriptasa inversa retroviral y la adn-polimerasa del virus de la hepatitis b (vhb).
ES01103370T Expired - Lifetime ES2239637T3 (es) 1997-08-15 1998-08-14 Derivados de guanosina 3'-fluorados para el tratamiento o profilaxis de vhb o infecciones retrovirales.

Family Applications After (1)

Application Number Title Priority Date Filing Date
ES01103370T Expired - Lifetime ES2239637T3 (es) 1997-08-15 1998-08-14 Derivados de guanosina 3'-fluorados para el tratamiento o profilaxis de vhb o infecciones retrovirales.

Country Status (23)

Country Link
EP (2) EP1123935B1 (es)
JP (1) JP3844654B2 (es)
KR (1) KR100529272B1 (es)
CN (2) CN1286845C (es)
AT (2) ATE200900T1 (es)
AU (1) AU728892B2 (es)
CA (1) CA2298704C (es)
CZ (1) CZ300757B6 (es)
DE (3) DE69829784T2 (es)
DK (1) DK0988304T3 (es)
ES (2) ES2158689T3 (es)
GR (1) GR3036004T3 (es)
HU (1) HU228060B1 (es)
IL (2) IL134503A0 (es)
MY (1) MY116269A (es)
NZ (1) NZ502837A (es)
PL (1) PL338643A1 (es)
PT (1) PT988304E (es)
SG (1) SG96604A1 (es)
SI (1) SI0988304T1 (es)
TR (2) TR200000398T2 (es)
TW (1) TW580500B (es)
WO (1) WO1999009031A1 (es)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6458772B1 (en) * 1909-10-07 2002-10-01 Medivir Ab Prodrugs
FR2794752A1 (fr) * 1999-06-11 2000-12-15 Laphal Sa Lab Nouveaux composes derives de nucleosides, leurs procedes de preparation, et les compositions pharmaceutiques en renfermant
FR2796384A1 (fr) * 1999-07-12 2001-01-19 Laphal Sa Lab Nouveaux esters derives de nucleosides, leurs procedes de preparation et les compositions pharmaceutiques en renfermant
MY141789A (en) 2001-01-19 2010-06-30 Lg Chem Investment Ltd Novel acyclic nucleoside phosphonate derivatives, salts thereof and process for the preparation of the same.
AUPS037002A0 (en) * 2002-02-07 2002-02-28 Melbourne Health Viral variants and uses therefor
WO2004087139A1 (en) 2003-03-27 2004-10-14 Boehringer Ingelheim International Gmbh Antiviral combination of tipranavir and a further antiretroviral compound
EP1610797A1 (en) * 2003-03-27 2006-01-04 Boehringer Ingelheim International GmbH Antiviral combination of nevirapine and a further antiretroviral compound
WO2004087140A1 (en) * 2003-03-27 2004-10-14 Boehringer Ingelheim International Gmbh Antiviral combination of a dipyridodiazepinone and a further antiretroviral compound
GB0400290D0 (en) 2004-01-08 2004-02-11 Medivir Ab dUTPase inhibitors
GB0513835D0 (en) 2005-07-07 2005-08-10 Medivir Ab HIV inhibitors
CN103347871A (zh) * 2011-02-21 2013-10-09 美迪维尔公司 Flg的合成
JP6830671B6 (ja) * 2015-09-23 2021-03-10 エックスダブリューファルマ リミテッド γ−ヒドロキシ酪酸（ＧＨＢ）のプロドラッグ、その組成物および使用
WO2021074443A1 (en) * 2019-10-17 2021-04-22 Ai-Biopharma Anti-viral and hepatic-targeted drugs
CN114686188B (zh) * 2020-12-31 2023-05-02 中石化石油工程技术服务有限公司 一种核苷磷脂钻井液润滑剂及其制备方法

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE8602981D0 (sv) * 1986-07-04 1986-07-04 Astra Laekemedel Ab Novel medicinal use
GB8719367D0 (en) * 1987-08-15 1987-09-23 Wellcome Found Therapeutic compounds
DE3883374T2 (de) * 1987-10-28 1993-12-09 Pro Neuron Inc Acylatiertes uridin und cytidin und deren verwendungen.
AU618436B2 (en) * 1988-12-19 1991-12-19 Wellcome Foundation Limited, The Antiviral cytosine and guanine derivatives
CA2444071C (en) * 1991-02-08 2008-10-07 Wellstat Therapeutics Corporation Oxypurine nucleosides and their congeners, and acyl derivatives thereof, for improvement of hematopoiesis
DE4311801A1 (de) * 1993-04-09 1994-10-13 Hoechst Ag Neue Carbonsäureester von 2-Amino-7-(1,3-dihydroxy-2-propoxymethyl)purin, deren Herstellung sowie deren Verwendung
PE32296A1 (es) * 1994-07-28 1996-08-07 Hoffmann La Roche Ester de l-monovalina derivado de 2-(2-amino-1,6-dihidro-6-oxo-purin-9-il) metoxi-1,3-propandiol y sus sales farmaceuticamente aceptables
WO1997027194A1 (en) * 1996-01-26 1997-07-31 F. Hoffmann-La Roche Ag Process for preparing purine derivatives
US5869493A (en) * 1996-02-16 1999-02-09 Medivir Ab Acyclic nucleoside derivatives
JP2001503767A (ja) * 1996-11-12 2001-03-21 メディヴィル・アクチボラグ ヌクレオシド

Also Published As

Publication number Publication date
CN1286845C (zh) 2006-11-29
JP3844654B2 (ja) 2006-11-15
DE69800753T2 (de) 2001-10-25
DE69800753T4 (de) 2002-02-21
ATE293112T1 (de) 2005-04-15
CZ300757B6 (cs) 2009-08-05
PL338643A1 (en) 2000-11-06
DE69800753D1 (de) 2001-06-07
IL134503A (en) 2010-06-30
TR200000398T2 (tr) 2000-07-21
GR3036004T3 (en) 2001-09-28
HUP0100087A3 (en) 2003-01-28
CZ2000449A3 (cs) 2000-08-16
EP0988304A1 (en) 2000-03-29
WO1999009031A1 (en) 1999-02-25
HK1097550A1 (zh) 2007-06-29
EP1123935A2 (en) 2001-08-16
MY116269A (en) 2003-12-31
ATE200900T1 (de) 2001-05-15
TW580500B (en) 2004-03-21
EP0988304B1 (en) 2001-05-02
HUP0100087A1 (hu) 2002-01-28
EP1123935A3 (en) 2001-09-05
EP1123935B1 (en) 2005-04-13
DE69829784T2 (de) 2006-02-16
AU8754898A (en) 1999-03-08
TR200002273T2 (tr) 2002-06-21
SG96604A1 (en) 2003-06-16
DE69829784D1 (de) 2005-05-19
ES2239637T3 (es) 2005-10-01
CN1500800A (zh) 2004-06-02
JP2001515079A (ja) 2001-09-18
SI0988304T1 (en) 2001-08-31
NZ502837A (en) 2001-01-26
HK1032968A1 (en) 2001-08-10
HU228060B1 (en) 2012-09-28
AU728892B2 (en) 2001-01-18
PT988304E (pt) 2001-10-31
KR20010022873A (ko) 2001-03-26
CA2298704C (en) 2006-07-11
CN1130362C (zh) 2003-12-10
IL134503A0 (en) 2001-04-30
KR100529272B1 (ko) 2005-11-17
CN1275983A (zh) 2000-12-06
DK0988304T3 (da) 2001-08-20
CA2298704A1 (en) 1999-02-25

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