CN1261099C - 四氢喹啉衍生物 - Google Patents

四氢喹啉衍生物 Download PDF

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Publication number
CN1261099C
CN1261099C CNB02813334XA CN02813334A CN1261099C CN 1261099 C CN1261099 C CN 1261099C CN B02813334X A CNB02813334X A CN B02813334XA CN 02813334 A CN02813334 A CN 02813334A CN 1261099 C CN1261099 C CN 1261099C
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CN
China
Prior art keywords
alkyl
amino
phenyl
aryl
acetyl
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 - Fee Related
Application number
CNB02813334XA
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English (en)
Chinese (zh)
Other versions
CN1529601A (zh
Inventor
N·C·R·范斯特拉藤
R·G·范索梅伦
J·舒尔兹
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.)
Merck Sharp and Dohme BV
Original Assignee
Akzo Nobel NV
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 Akzo Nobel NV filed Critical Akzo Nobel NV
Publication of CN1529601A publication Critical patent/CN1529601A/zh
Application granted granted Critical
Publication of CN1261099C publication Critical patent/CN1261099C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/38—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • 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
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P15/16—Masculine contraceptives
    • 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
    • A61P15/18—Feminine contraceptives
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • 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
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • 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
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • A61P5/08—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
    • 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
    • A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
    • 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
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C07D215/08—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/20—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Quinoline Compounds (AREA)
CNB02813334XA 2001-07-02 2002-06-25 四氢喹啉衍生物 Expired - Fee Related CN1261099C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP01202531.8 2001-07-02
EP01202531 2001-07-02

Publications (2)

Publication Number Publication Date
CN1529601A CN1529601A (zh) 2004-09-15
CN1261099C true CN1261099C (zh) 2006-06-28

Family

ID=8180574

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB02813334XA Expired - Fee Related CN1261099C (zh) 2001-07-02 2002-06-25 四氢喹啉衍生物

Country Status (31)

Country Link
US (2) US8058441B2 (https=)
EP (1) EP1406628B1 (https=)
JP (1) JP4523273B2 (https=)
KR (1) KR100908468B1 (https=)
CN (1) CN1261099C (https=)
AR (1) AR034669A1 (https=)
AT (1) ATE319451T1 (https=)
AU (1) AU2002317848B2 (https=)
BR (1) BR0210645A (https=)
CA (1) CA2452606C (https=)
CY (1) CY1106087T1 (https=)
CZ (1) CZ20042A3 (https=)
DE (1) DE60209734T2 (https=)
DK (1) DK1406628T3 (https=)
EC (1) ECSP034932A (https=)
ES (1) ES2260458T3 (https=)
HR (1) HRP20031080A2 (https=)
HU (1) HUP0400390A2 (https=)
IL (1) IL159288A0 (https=)
IS (1) IS2418B (https=)
MX (1) MXPA03011908A (https=)
NO (1) NO325516B1 (https=)
NZ (1) NZ530198A (https=)
PE (1) PE20030273A1 (https=)
PL (1) PL367638A1 (https=)
PT (1) PT1406628E (https=)
RU (1) RU2347570C2 (https=)
SA (1) SA02230260B1 (https=)
SK (1) SK286759B6 (https=)
WO (1) WO2003004028A1 (https=)
ZA (1) ZA200309921B (https=)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ20042A3 (en) * 2001-07-02 2004-04-14 Akzo Nobel N. V. Tetrahydroquinoline derivatives
AU2003245773A1 (en) * 2002-02-15 2003-09-04 Glaxo Group Limited Vanilloid receptor modulators
FR2836620B1 (fr) * 2002-02-28 2004-04-16 Snecma Services Instrument de projection thermique
SE0200920D0 (sv) * 2002-03-25 2002-03-25 Astrazeneca Ab Novel compounds
TWI322012B (en) * 2002-12-20 2010-03-21 Organon Nv Tetrahydroquinoline derivatives
TWI306855B (en) * 2002-12-20 2009-03-01 Organon Nv Tetrahydroquinoline derivatives
SE0300480D0 (sv) * 2003-02-21 2003-02-21 Astrazeneca Ab Novel compounds
WO2004105797A1 (en) * 2003-05-29 2004-12-09 Astrazeneca Ab A pharmaceutical composition comprising a p2x7 antagonist and sulfasalazine
US20070281931A1 (en) * 2003-05-29 2007-12-06 Nigel Boughton-Smith Pharmaceutical Composition Containing a P2x7 Receptor Antagonist and Methotrexate
MXPA05012705A (es) * 2003-05-29 2006-02-08 Astrazeneca Ab Una composicion farmaceutica que comprende un antagonista del receptor p2x7 y un factor alfa de necrosis tumoral.
GB0312609D0 (en) * 2003-06-02 2003-07-09 Astrazeneca Ab Novel compounds
KR100554155B1 (ko) * 2003-06-09 2006-02-22 학교법인 포항공과대학교 금속/반도체 나노막대 이종구조를 이용한 전극 구조물 및그 제조 방법
SE0302139D0 (sv) * 2003-07-28 2003-07-28 Astrazeneca Ab Novel compounds
SE0302192D0 (sv) * 2003-08-08 2003-08-08 Astrazeneca Ab Novel compounds
SE0302488D0 (sv) * 2003-09-18 2003-09-18 Astrazeneca Ab New combination
SA05260265A (ar) * 2004-08-30 2005-12-03 استرازينيكا ايه بي مركبات جديدة
SE0402925D0 (sv) * 2004-11-30 2004-11-30 Astrazeneca Ab Novel Compounds
US7691848B2 (en) 2005-03-02 2010-04-06 Wyeth Pyrrolobenzodiazepine arylcarboxamides and derivatives thereof as follicle-stimulating hormone receptor antagonists
UA92009C2 (ru) 2005-05-04 2010-09-27 Н.В. Органон Производные 4-фенил-5-оксо-1,4,5,6,7,8-гексагидрохинолина для лечения бесплодия
RS51784B (sr) 2005-05-04 2011-12-31 N.V. Organon Derivati dihidropiridina
UA92008C2 (en) * 2005-05-04 2010-09-27 Н.В. Органон 4-PHENYL-5-OXO-l,4,5,6,7,8-HEXAHYDROQUINOLINE DERIVATIVES AS MEDICAMENTS FOR THE TREATMENT OF INFERTILITY
UA92007C2 (ru) * 2005-05-04 2010-09-27 Н.В. Органон Производные 4-фенил-5-оксо-1,4,5,6,7,8-гексагидрохинолина для лечения бесплодности
EP1879898A2 (en) 2005-05-12 2008-01-23 Wyeth a Corporation of the State of Delaware Pyrrolobenzodiazepines and heterocyclic carboxamide derivatives as follicle stimulating hormone receptor (fsh-r) antagonists
EP1893615A1 (en) 2005-06-09 2008-03-05 Wyeth a Corporation of the State of Delaware Pyrrolobenzodiazepine pyridine carboxamides and derivatives as follicle-stimulating hormone receptor antagonists
US20070060573A1 (en) * 2005-08-10 2007-03-15 Lars Wortmann Acyltryptophanols
CA2618888A1 (en) * 2005-08-10 2007-02-15 Bayer Schering Pharma Aktiengesellschaft Acyltryptophanols for fertility control
EP1932831A1 (en) * 2006-12-13 2008-06-18 Bayer Schering Pharma Aktiengesellschaft 1,2-Diarylacetylene Derivatives of Acyltryptophanols
US20080221195A1 (en) * 2006-12-13 2008-09-11 Lars Wortmann 1,2-diarylacetylene derivatives of acyltryptophanols
TWI410422B (zh) * 2007-01-15 2013-10-01 Mitsubishi Tanabe Pharma Corp 縮合四氫喹啉衍生物及其醫藥用途
TW200848021A (en) 2007-03-06 2008-12-16 Wyeth Corp Sulfonylated heterocycles useful for modulation of the progesterone receptor
CA2680761A1 (en) * 2007-03-22 2008-09-25 Astrazeneca Ab Quinoline derivatives for the treatment of inflammatory diseases
TW200918058A (en) * 2007-08-31 2009-05-01 Organon Nv TSH receptor antagonizing tetrahydroquinoline compounds
PE20091036A1 (es) 2007-11-30 2009-08-15 Astrazeneca Ab Derivado de quinolina como antagonista del receptor p2x7
RU2359684C1 (ru) * 2008-01-23 2009-06-27 Закрытое акционерное общество "СКАЙ ЛТД" Способ лечения эндометриоза
TW200944523A (en) 2008-02-08 2009-11-01 Organon Nv (Dihydro)pyrrolo[2,1-a]isoquinolines
US20100061976A1 (en) * 2008-07-24 2010-03-11 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Method for treating or preventing osteoporosis by reducing follicle stimulating hormone to cyclic physiological levels in a mammalian subject
US8071587B2 (en) 2009-05-27 2011-12-06 N. V. Organon (Dihydro)imidazoiso[5,1-A]quinolines
TWI461426B (zh) * 2009-05-27 2014-11-21 Merck Sharp & Dohme （二氫）咪唑並異〔５，１－ａ〕喹啉類
TW201116531A (en) 2009-07-29 2011-05-16 Organon Nv Ring-annulated dihydropyrrolo[2,1-a]isoquinolines
US8431564B2 (en) 2009-07-29 2013-04-30 Merck Sharp & Dohme B.V. Ring-annulated dihydropyrrolo[2,1-α]isoquinolines
TW201116515A (en) 2009-07-31 2011-05-16 Organon Nv Dihydrobenzoindazoles
DK2624695T3 (en) * 2010-10-08 2016-01-04 Nivalis Therapeutics Inc NOVEL SUBSTITUTED quinoline-RELATIONS AS S-NITROSOGLUTATHIONREDUKTASEINHIBITORER
US8546427B2 (en) * 2010-10-20 2013-10-01 Hoffmann-La Roche Inc. Tetrahydroquinoline derivatives
WO2016018553A1 (en) * 2014-07-30 2016-02-04 Henkel IP & Holding GmbH Cure accelerators for anaerobic curable compositions
WO2019089412A1 (en) * 2017-11-01 2019-05-09 Merck Sharp & Dohme Corp. Novel substituted tetrahydroquinolin compounds as indoleamine 2,3-dioxygenase (ido) inhibitors
CN119954701A (zh) * 2024-06-18 2025-05-09 青岛润农化工有限公司 一种丁醚脲的合成方法

Family Cites Families (9)

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US2686182A (en) 1950-12-07 1954-08-10 Basf Ag O-hydroxy-dihydro-quinoline carboxylic acids
EP0303306B1 (en) 1987-08-08 1993-03-10 Akzo N.V. Contraceptive implant
EP1043325B1 (en) * 1994-12-22 2004-06-16 Ligand Pharmaceuticals Incorporated Steroid receptor modulator compounds and methods
US6235755B1 (en) * 1998-08-07 2001-05-22 Applied Research Systems Ars Holding N.A. FSH mimetics for the treatment of infertility
JP2000143636A (ja) * 1998-09-02 2000-05-26 Sumitomo Pharmaceut Co Ltd アミノ誘導体
US6200963B1 (en) * 1999-03-31 2001-03-13 American Home Products Corporation Aryl sulfonic acids as FSH antagonists
CZ20042A3 (en) 2001-07-02 2004-04-14 Akzo Nobel N. V. Tetrahydroquinoline derivatives
TWI306855B (en) 2002-12-20 2009-03-01 Organon Nv Tetrahydroquinoline derivatives
TWI322012B (en) 2002-12-20 2010-03-21 Organon Nv Tetrahydroquinoline derivatives

Also Published As

Publication number Publication date
CA2452606C (en) 2011-09-13
ES2260458T3 (es) 2006-11-01
SK286759B6 (sk) 2009-05-07
SK16342003A3 (sk) 2004-07-07
IL159288A0 (en) 2004-06-01
HUP0400390A2 (hu) 2004-09-28
KR20040030714A (ko) 2004-04-09
KR100908468B1 (ko) 2009-07-21
MXPA03011908A (es) 2004-06-03
RU2347570C2 (ru) 2009-02-27
DE60209734D1 (de) 2006-05-04
CA2452606A1 (en) 2003-01-16
ZA200309921B (en) 2005-03-22
CY1106087T1 (el) 2011-06-08
EP1406628A1 (en) 2004-04-14
NO325516B1 (no) 2008-06-02
IS2418B (is) 2008-10-15
BR0210645A (pt) 2004-10-05
CZ20042A3 (en) 2004-04-14
RU2004102693A (ru) 2005-06-27
JP4523273B2 (ja) 2010-08-11
NO20035763L (no) 2003-12-29
ATE319451T1 (de) 2006-03-15
SA02230260B1 (ar) 2007-03-25
PL367638A1 (en) 2005-03-07
US20120202996A1 (en) 2012-08-09
DE60209734T2 (de) 2006-08-31
US20040236109A1 (en) 2004-11-25
PT1406628E (pt) 2006-06-30
CN1529601A (zh) 2004-09-15
HK1061810A1 (en) 2004-10-08
AU2002317848B2 (en) 2006-08-31
NZ530198A (en) 2005-11-25
HRP20031080A2 (en) 2004-04-30
JP2004535456A (ja) 2004-11-25
ECSP034932A (es) 2004-02-26
US8058441B2 (en) 2011-11-15
US8258293B2 (en) 2012-09-04
PE20030273A1 (es) 2003-03-21
IS7071A (is) 2003-12-11
AR034669A1 (es) 2004-03-03
DK1406628T3 (da) 2006-07-03
WO2003004028A1 (en) 2003-01-16
EP1406628B1 (en) 2006-03-08

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