PT1274411E - Feniletilaminas e variantes de aneis condensados como pro-farmacos de catecolaminas, e sua utilizacao - Google Patents

Feniletilaminas e variantes de aneis condensados como pro-farmacos de catecolaminas, e sua utilizacao

Info

Publication number
PT1274411E
PT1274411E PT01922208T PT01922208T PT1274411E PT 1274411 E PT1274411 E PT 1274411E PT 01922208 T PT01922208 T PT 01922208T PT 01922208 T PT01922208 T PT 01922208T PT 1274411 E PT1274411 E PT 1274411E
Authority
PT
Portugal
Prior art keywords
carbon atoms
alkyl
rings
groups
group
Prior art date
Application number
PT01922208T
Other languages
English (en)
Portuguese (pt)
Inventor
Hakan Wikstrom
Dijkstra Durk
Venhuis Bastiaan Johan
Original Assignee
Lundbeck & Co As H
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
Application filed by Lundbeck & Co As H filed Critical Lundbeck & Co As H
Publication of PT1274411E publication Critical patent/PT1274411E/pt

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide
    • 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
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/02—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C225/14—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/20—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
    • 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
    • C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen 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
    • C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/08—Aza-anthracenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/10—Aza-phenanthrenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/18—Ring systems of four or more rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
    • C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Psychiatry (AREA)
  • Endocrinology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic 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)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Medicinal Preparation (AREA)
PT01922208T 2000-04-18 2001-04-17 Feniletilaminas e variantes de aneis condensados como pro-farmacos de catecolaminas, e sua utilizacao PT1274411E (pt)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
SE0001438A SE0001438D0 (sv) 2000-04-18 2000-04-18 New chemical compounds and their use in therapy

Publications (1)

Publication Number Publication Date
PT1274411E true PT1274411E (pt) 2005-11-30

Family

ID=20279367

Family Applications (1)

Application Number Title Priority Date Filing Date
PT01922208T PT1274411E (pt) 2000-04-18 2001-04-17 Feniletilaminas e variantes de aneis condensados como pro-farmacos de catecolaminas, e sua utilizacao

Country Status (19)

Country Link
US (4) US6683087B2 (enExample)
EP (1) EP1274411B1 (enExample)
JP (1) JP4819280B2 (enExample)
CN (2) CN100383126C (enExample)
AT (1) ATE300290T1 (enExample)
AU (2) AU4898201A (enExample)
CA (1) CA2406044C (enExample)
CZ (1) CZ20023455A3 (enExample)
DE (1) DE60112269T2 (enExample)
DK (1) DK1274411T3 (enExample)
ES (1) ES2244604T3 (enExample)
HU (1) HU229794B1 (enExample)
NZ (1) NZ521860A (enExample)
PL (1) PL204661B1 (enExample)
PT (1) PT1274411E (enExample)
SE (1) SE0001438D0 (enExample)
SI (1) SI1274411T1 (enExample)
WO (1) WO2001078713A1 (enExample)
ZA (1) ZA200207919B (enExample)

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US7910623B2 (en) * 2005-07-22 2011-03-22 Sloan-Kettering Institute For Cancer Research Synthesis of scabronines and analogues thereof
WO2007013830A1 (en) 2005-07-26 2007-02-01 Portela & Ca. S.A. Nitrocatechol derivatives as comt inhibitors
EP1845097A1 (en) * 2006-04-10 2007-10-17 Portela & Ca., S.A. Oxadiazole derivatives as COMT inhibitors
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US20090124651A1 (en) 2007-08-31 2009-05-14 H. Lundbeck A/S Catecholamine derivatives and prodrugs thereof
BRPI0908731A2 (pt) 2008-03-17 2017-05-16 Bial - Portela & C A S A formas cristalinas de 5-[3-(2,5-dicloro-4,6-dimetil-1-óxi-piridina-3-il)[1,2,4]oxadiazol-5-il]-3-nitrobenzeno-1,2-diol
TW201036949A (en) * 2009-02-27 2010-10-16 Lundbeck & Co As H Treatment of dyskinesia related disorders
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US8492538B1 (en) * 2009-06-04 2013-07-23 Jose R. Matos Cyclodextrin derivative salts
US8558016B2 (en) * 2009-09-18 2013-10-15 Kabaushiki Kaisha Riverson Polyphenol derivative and method for producing the same
US20140045900A1 (en) 2011-02-11 2014-02-13 Bial-Portela & Ca, S.A. Administration regime for nitrocatechols
US9126988B2 (en) 2011-12-13 2015-09-08 Bial—Portela & Ca, S.A. Intermediate for preparing a catechol-O-methyltransferase inhibitor
WO2016083863A1 (en) 2014-11-28 2016-06-02 Bial - Portela & Ca, S.A. Medicaments for slowing parkinson's disease
PT3713933T (pt) 2017-11-24 2026-05-19 H Lundbeck As Novos profrmacos de catecolamina para utilizao no tratamento de doena de parkinson
US11111263B2 (en) 2019-05-20 2021-09-07 H. Lundbeck A/S Process for the manufacture of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid
US11104697B2 (en) 2019-05-20 2021-08-31 H. Lundbeck A/S Process for the manufacture of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4AR,10AR)-7-hydroxy-1- propyl-1,2,3,4,4A,5,10,10A-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid
US11168056B2 (en) 2019-05-20 2021-11-09 H. Lundbeck A/S Process for the manufacturing of (6aR,10aR)-7-propyl-6,6a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4′,5′:5,6]benzo[1,2-G]quinoline and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[G]quinoline-6,7-diol
US11130775B2 (en) 2019-05-20 2021-09-28 H. Lundbeck A/S Solid forms of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4A,5,10,10A-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid
US12391650B2 (en) 2019-05-21 2025-08-19 H. Lundbeck A/S Catecholamine prodrugs for use in the treatment of Parkinson's disease
EP3972600B1 (en) 2019-05-21 2026-02-18 H. Lundbeck A/S Catecholamine carbamate prodrugs for use in the treatment of parkinson s disease
WO2020234275A1 (en) 2019-05-21 2020-11-26 H. Lundbeck A/S New catecholamine prodrugs for use in the treatment of parkinson's diseases
JP7641234B2 (ja) 2019-05-21 2025-03-06 ハー・ルンドベック・アクチエゼルスカベット パーキンソン病の治療に使用するための新規なカテコールアミンプロドラッグ
WO2022106352A1 (en) 2020-11-17 2022-05-27 H. Lundbeck A/S New catecholamine prodrugs for use in the treatment of parkinson's disease
JP2025514341A (ja) 2022-04-25 2025-05-02 インテグレーティブ リサーチ ラボラトリーズ スウェーデン アーベー 新規1,2,3,4,4a,5,6,7,8,9,10,10a-ドデカヒドロベンゾ[G]キノリン-6-オール化合物及びその使用
JP2025513617A (ja) 2022-04-25 2025-04-24 インテグレーティブ リサーチ ラボラトリーズ スウェーデン アーベー 1,2,3,4,4a,5,6,7,8,9,10,10a-ドデカヒドロベンゾ[g]キノリン-6-オール化合物の新規エステル及びその使用
WO2023208867A1 (en) 2022-04-25 2023-11-02 Integrative Research Laboratories Sweden Ab NOVEL 1,2,3,4,4a,5,8,9,10,10a-DECAHYDROBENZO[G]QUINOLIN-6(7H)-ONE COMPOUNDS AND USES THEREOF
WO2025078574A1 (en) 2023-10-12 2025-04-17 Integrative Research Laboratories Sweden Ab NOVEL ESTERS OF 1,2,3,4,4a,5,6,7,8,9,10,10a-DODECAHYDROBENZO[g]QUINOLIN-6-OL COMPOUNDS AND USES THEREOF
WO2025078571A1 (en) 2023-10-12 2025-04-17 Integrative Research Laboratories Sweden Ab NOVEL CARBONATES AND CARBAMATES OF 1,2,3,4,4a,5,6,7,8,9,10,10a- DODECAHYDROBENZO[g]QUINOLIN-6-OL COMPOUNDS AND USES THEREOF

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Also Published As

Publication number Publication date
ATE300290T1 (de) 2005-08-15
US6683087B2 (en) 2004-01-27
AU4898201A (en) 2001-10-30
NZ521860A (en) 2004-03-26
HUP0300543A2 (hu) 2003-07-28
HUP0300543A3 (en) 2009-04-28
PL204661B1 (pl) 2010-01-29
US20030087948A1 (en) 2003-05-08
WO2001078713A1 (en) 2001-10-25
US20040138281A1 (en) 2004-07-15
PL365113A1 (en) 2004-12-27
SE0001438D0 (sv) 2000-04-18
HK1088009A1 (en) 2006-10-27
CN1781910A (zh) 2006-06-07
USRE43244E1 (en) 2012-03-13
CN100383126C (zh) 2008-04-23
ZA200207919B (en) 2003-10-02
SI1274411T1 (sl) 2005-12-31
EP1274411B1 (en) 2005-07-27
DK1274411T3 (da) 2005-11-14
CZ20023455A3 (cs) 2003-04-16
AU2001248982B2 (en) 2005-12-15
DE60112269D1 (de) 2005-09-01
ES2244604T3 (es) 2005-12-16
CN1450894A (zh) 2003-10-22
USRE42802E1 (en) 2011-10-04
DE60112269T2 (de) 2006-05-24
CA2406044C (en) 2009-10-27
EP1274411A1 (en) 2003-01-15
JP2004500426A (ja) 2004-01-08
JP4819280B2 (ja) 2011-11-24
US6998405B2 (en) 2006-02-14
HU229794B1 (hu) 2014-07-28
CN1234351C (zh) 2006-01-04
CA2406044A1 (en) 2001-10-25

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