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NO20054876L - Substituerte 4-fenyltetrahydroisokinoliner, fremgangsmate for fremstilling derav, deres anvendelse som medikament og medikament inneholdende slike forbindelser - Google Patents

Substituerte 4-fenyltetrahydroisokinoliner, fremgangsmate for fremstilling derav, deres anvendelse som medikament og medikament inneholdende slike forbindelser

Info

Publication number
NO20054876L
NO20054876L NO20054876A NO20054876A NO20054876L NO 20054876 L NO20054876 L NO 20054876L NO 20054876 A NO20054876 A NO 20054876A NO 20054876 A NO20054876 A NO 20054876A NO 20054876 L NO20054876 L NO 20054876L
Authority
NO
Norway
Prior art keywords
drug
compounds
phenyltetrahydroisoquinolines
substituted
preparation
Prior art date
Application number
NO20054876A
Other languages
English (en)
Other versions
NO20054876D0 (no
Inventor
Klaus Wirth
Hans-Jochen Lang
Wendelin Frick
Armin Hofmeister
Markus Bleich
Uwe Heinelt
Original Assignee
Sanofi Aventis Deutschland
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 Sanofi Aventis Deutschland filed Critical Sanofi Aventis Deutschland
Publication of NO20054876D0 publication Critical patent/NO20054876D0/no
Publication of NO20054876L publication Critical patent/NO20054876L/no

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/472Non-condensed isoquinolines, e.g. papaverine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • A61P33/02Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • A61P33/02Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06Antimalarials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/02Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D217/00Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
    • C07D217/16Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Psychiatry (AREA)
  • Obesity (AREA)
  • Pain & Pain Management (AREA)
  • Pulmonology (AREA)
  • Transplantation (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

Det beskrives forbindelser med formel I der RI til R9 har de angitte betydninger. Medikamenter inneholdende denne type forbindelse, kan benyttes ved prevensjon eller terapi av forskjellige sykdommer. Forbindelsene kan blant annet benyttes for renale sykdommer som akutt eller kronisk nyresvikt, for forstyrrelser i biliarfunksjonene eller mot respiratoriske forstyrrelser, som snorking eller søvnapne, eller mot apopleksi.
NO20054876A 2003-03-24 2005-10-21 Substituerte 4-fenyltetrahydroisokinoliner, fremgangsmate for fremstilling derav, deres anvendelse som medikament og medikament inneholdende slike forbindelser NO20054876L (no)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10312963A DE10312963A1 (de) 2003-03-24 2003-03-24 Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
PCT/EP2004/002497 WO2004085404A1 (de) 2003-03-24 2004-03-11 Substituierte 4-phenyltetrahydroisochinoline, verfahren zu ihrer herstellung, ihre verwendung als medikament, sowie sie enthaltendes medikament

Publications (2)

Publication Number Publication Date
NO20054876D0 NO20054876D0 (no) 2005-10-21
NO20054876L true NO20054876L (no) 2005-12-06

Family

ID=32946086

Family Applications (1)

Application Number Title Priority Date Filing Date
NO20054876A NO20054876L (no) 2003-03-24 2005-10-21 Substituerte 4-fenyltetrahydroisokinoliner, fremgangsmate for fremstilling derav, deres anvendelse som medikament og medikament inneholdende slike forbindelser

Country Status (22)

Country Link
EP (1) EP1613600B1 (no)
JP (1) JP2006521306A (no)
KR (1) KR20050115304A (no)
CN (1) CN100364978C (no)
AR (1) AR043741A1 (no)
AU (1) AU2004224242B2 (no)
BR (1) BRPI0408744A (no)
CA (1) CA2519658A1 (no)
DE (1) DE10312963A1 (no)
HR (1) HRP20050843A2 (no)
MA (1) MA27751A1 (no)
ME (1) MEP42908A (no)
MX (1) MXPA05010003A (no)
MY (1) MY139498A (no)
NO (1) NO20054876L (no)
NZ (1) NZ542608A (no)
PE (1) PE20050311A1 (no)
RS (1) RS20050713A (no)
RU (1) RU2343147C2 (no)
TW (1) TW200510321A (no)
WO (1) WO2004085404A1 (no)
ZA (1) ZA200506422B (no)

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* Cited by examiner, † Cited by third party
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DE102004046492A1 (de) * 2004-09-23 2006-03-30 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
DE102005001411A1 (de) 2005-01-12 2006-07-27 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
DE102005033100B3 (de) * 2005-07-15 2007-01-25 Sanofi-Aventis Deutschland Gmbh Neues 1,4-Benzothiazepin-1,1-Dioxidderivat mit verbesserten Eigenschaften, diese Verbindung enthaltene Arzneimittel und Verfahren zu deren Herstellung
DE102005044817A1 (de) * 2005-09-20 2007-03-22 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
DE102006012544A1 (de) * 2006-03-18 2007-09-27 Sanofi-Aventis Substituierte 1-Amino 4-phenyl-dihydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
EP2592070B1 (en) * 2006-06-29 2016-08-31 F. Hoffmann-La Roche AG Tetrazole-substituted arylamides
JPWO2008004610A1 (ja) * 2006-07-05 2009-12-03 国立大学法人 東京大学 ナンセンス変異型遺伝性疾患の治療方法
AU2009250843A1 (en) * 2008-05-19 2009-11-26 Actelion Pharmaceuticals Ltd Tetrahydroisoquinolines as antimalarial agents
KR20200111230A (ko) * 2008-12-31 2020-09-28 알데릭스, 인코포레이티드 체액 저류 또는 염 과부하와 연관된 장애 및 위장관 장애의 치료 시에 nhe-매개된 역수송을 억제하는 화합물 및 방법
WO2018129556A1 (en) * 2017-01-09 2018-07-12 Ardelyx, Inc. Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
US10543207B2 (en) 2008-12-31 2020-01-28 Ardelyx, Inc. Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
ES2644082T3 (es) * 2011-08-25 2017-11-27 St. Jude Children's Research Hospital 2-alquil-1-oxo-n-fenil-3-heteroaril-1,2,3,4-tetrahidroisoquinolina-4-carboxamidas sustituidas para tratamientos antipalúdicos
RS58969B1 (sr) * 2013-04-12 2019-08-30 Ardelyx Inc Jedinjenja koja se vezuju za nhe3 i postupci za inhibiranje transporta fosfata
RU2538085C2 (ru) * 2013-05-08 2015-01-10 Любовь Демьяновна Шаманская Препарат для борьбы с экзопаразитами животных
KR102386666B1 (ko) 2014-07-25 2022-04-15 다이쇼 세이야꾸 가부시끼가이샤 헤테로아릴로 치환된 페닐테트라히드로이소퀴놀린 화합물
KR20240090875A (ko) 2017-01-09 2024-06-21 알데릭스, 인코포레이티드 위장관 장애를 치료하는 데 유용한 화합물
CA3049679A1 (en) 2017-01-09 2018-07-12 Ardelyx, Inc. Inhibitors of nhe-mediated antiport
WO2018165520A1 (en) 2017-03-10 2018-09-13 Vps-3, Inc. Metalloenzyme inhibitor compounds
BR112021019936A2 (pt) * 2019-05-16 2021-12-07 Lilly Co Eli Compostos inibidores de permutador 3 de sódio-hidrogênio
CA3149096A1 (en) 2019-07-30 2021-02-04 Eikonizo Therapapeutics, Inc. Hdac6 inhibitors and uses thereof

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US3666763A (en) * 1970-01-06 1972-05-30 Hoffmann La Roche 4-phenyl isoquinolines and process for preparing same
JPH06256311A (ja) * 1993-02-26 1994-09-13 Nippon Shinyaku Co Ltd イソキノリノール誘導体及び医薬
GB9322828D0 (en) * 1993-11-05 1993-12-22 Sandoz Ltd Organic compounds
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DE19951702A1 (de) * 1999-10-27 2001-05-03 Aventis Pharma Gmbh Verwendung von 2-Amino-3,4-dihydro-chinazolinen zur Herstellung eines Medikaments zur Behandlung oder Prophylaxe von durch ischämischen Zuständen bewirkten Krankheiten
KR100885986B1 (ko) * 1999-11-03 2009-03-03 에이엠알 테크놀로지, 인크. 노르에피네프린, 도파민 및 세로토닌의 재흡수를 방지하기위한 아릴 및 헤테로아릴 치환된테트라하이드로이소퀴놀린 및 이들의 용도
WO2001032624A1 (en) * 1999-11-03 2001-05-10 Du Pont Pharmaceuticals Company 4-phenyl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin
EP1113007A1 (en) * 1999-12-24 2001-07-04 Pfizer Inc. Tetrahydroisoquinoline compounds as estrogen agonists/antagonists
WO2003048129A1 (de) * 2001-12-05 2003-06-12 Aventis Pharma Deutschland Gmbh Substituierte 4-phenyltetrahydroisochinoline, verfahren zu ihrer herstellung, ihre verwendung als medikament, sowie sie enthaltendes medikament
DE10161767A1 (de) * 2001-12-15 2003-06-26 Merck Patent Gmbh 2-Guanidino-4-heterocyclyl-chinazoline
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Also Published As

Publication number Publication date
NO20054876D0 (no) 2005-10-21
HRP20050843A2 (en) 2006-09-30
RU2343147C2 (ru) 2009-01-10
EP1613600A1 (de) 2006-01-11
WO2004085404A1 (de) 2004-10-07
CA2519658A1 (en) 2004-10-07
EP1613600B1 (de) 2015-12-23
RS20050713A (sr) 2007-11-15
AR043741A1 (es) 2005-08-10
KR20050115304A (ko) 2005-12-07
MXPA05010003A (es) 2005-11-17
AU2004224242A1 (en) 2004-10-07
NZ542608A (en) 2009-07-31
CN1798737A (zh) 2006-07-05
MEP42908A (en) 2011-02-10
PE20050311A1 (es) 2005-06-06
AU2004224242B2 (en) 2010-03-18
TW200510321A (en) 2005-03-16
ZA200506422B (en) 2007-02-28
BRPI0408744A (pt) 2006-04-18
RU2006127170A (ru) 2008-02-10
DE10312963A1 (de) 2004-10-07
CN100364978C (zh) 2008-01-30
JP2006521306A (ja) 2006-09-21
HK1090042A1 (en) 2006-12-15
MA27751A1 (fr) 2006-02-01
MY139498A (en) 2009-10-30

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