CN1968929B - 取代的四氢-2h-异喹啉-1-酮衍生物、其制备方法以及其作为药物的用途 - Google Patents

取代的四氢-2h-异喹啉-1-酮衍生物、其制备方法以及其作为药物的用途 Download PDF

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Publication number
CN1968929B
CN1968929B CN2005800201245A CN200580020124A CN1968929B CN 1968929 B CN1968929 B CN 1968929B CN 2005800201245 A CN2005800201245 A CN 2005800201245A CN 200580020124 A CN200580020124 A CN 200580020124A CN 1968929 B CN1968929 B CN 1968929B
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alkyl
isoquinolin
methyl
tetrahydro
compound
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Chinese (zh)
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CN1968929A (zh
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S·波伊克特
S·居斯雷根
A·霍夫迈斯特
H·施罗伊德
U·施万
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Sanofi Aventis Deutschland GmbH
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • A61P25/28—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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • 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
    • A61P9/10—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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms
    • 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
    • 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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • 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)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Neurology (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Vascular Medicine (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Psychiatry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
CN2005800201245A 2004-06-16 2005-06-01 取代的四氢-2h-异喹啉-1-酮衍生物、其制备方法以及其作为药物的用途 Expired - Fee Related CN1968929B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE102004028973A DE102004028973A1 (de) 2004-06-16 2004-06-16 Substituierte Tetrahydro-2H-isochinolin-1-on-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Medikament
DE102004028973.5 2004-06-16
PCT/EP2005/005871 WO2005123687A1 (de) 2004-06-16 2005-06-01 Substituierte tetrahydro-2h-isochinolin-1-on-derivate, verfahren zu ihrer herstellung und ihre verwendung als medikament

Publications (2)

Publication Number Publication Date
CN1968929A CN1968929A (zh) 2007-05-23
CN1968929B true CN1968929B (zh) 2010-09-08

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CN2005800201245A Expired - Fee Related CN1968929B (zh) 2004-06-16 2005-06-01 取代的四氢-2h-异喹啉-1-酮衍生物、其制备方法以及其作为药物的用途

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US (2) US7795278B2 (https=)
EP (1) EP1758864B1 (https=)
JP (1) JP4928446B2 (https=)
KR (1) KR101169919B1 (https=)
CN (1) CN1968929B (https=)
AU (1) AU2005254632B2 (https=)
BR (1) BRPI0512139A (https=)
CA (1) CA2570942C (https=)
DE (1) DE102004028973A1 (https=)
IL (1) IL179758A (https=)
MX (1) MXPA06013876A (https=)
WO (1) WO2005123687A1 (https=)

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PE20080176A1 (es) 2006-03-31 2008-04-25 Glaxo Group Ltd Compuestos de arilpiperazina sulfonamida como agonista de los receptores de secretagogos de la hormona de crecimiento (ghs)
CN102099036B (zh) 2008-06-03 2015-05-27 英特芒尼公司 用于治疗炎性疾患和纤维化疾患的化合物和方法
US8735391B2 (en) 2008-09-26 2014-05-27 University Of Kansas Synthesis of functionalized octahydro-isoquinolin-1-one-8-carboxamides, octahydro-isoquinolin-1-one-8-carboxylic esters and analogs, and therapeutic methods
AU2009314760B2 (en) * 2008-11-11 2011-11-10 Je Il Pharmaceutical Co.,Ltd Novel tricyclic derivative or pharmaceutically acceptable salts thereof, preparation method thereof, and pharmaceutical composition containing the same
WO2010081778A1 (en) 2009-01-17 2010-07-22 Universität Zürich Blockers of parp for the prevention and treatment of helicobacter pylori induced gastric cancer
TWI499418B (zh) * 2009-05-21 2015-09-11 Nerviano Medical Sciences Srl 異喹啉－１（２ｈ）－酮衍生物
CN101602725B (zh) * 2009-07-21 2012-07-11 浙江大学 六氢异喹啉酮类化合物的合成方法
WO2011058367A2 (en) 2009-11-13 2011-05-19 Astrazeneca Ab Diagnostic test for predicting responsiveness to treatment with poly(adp-ribose) polymerase (parp) inhibitor
JP2013531687A (ja) 2010-07-16 2013-08-08 パーデュー、ファーマ、リミテッド、パートナーシップ ナトリウムチャネル遮断剤としてのピリジン化合物
WO2013136170A1 (en) 2012-03-16 2013-09-19 Purdue Pharma L.P. Substituted pyridines as sodium channel blockers
AR092742A1 (es) * 2012-10-02 2015-04-29 Intermune Inc Piridinonas antifibroticas
EP2935257B1 (en) 2012-12-20 2018-02-07 Purdue Pharma LP Cyclic sulfonamides as sodium channel blockers
MX382781B (es) 2014-04-02 2025-03-13 Intermune Inc Piridinonas anti-fibroticas.
US10730866B2 (en) 2014-04-07 2020-08-04 Purdue Pharma L.P. Indole derivatives and use thereof
CN105272936B (zh) * 2014-05-27 2019-05-17 中国科学院上海药物研究所 一类氮芳基苯并噻唑类parp抑制剂及其制备方法和用途
CN104163796A (zh) * 2014-08-04 2014-11-26 上海师范大学 一类取代的1,2,3,4-四氢喹啉-4-酮盐酸盐的制备方法
MX375707B (es) * 2015-06-09 2025-03-06 Onconic Therapeutics Inc Compuesto derivativo triciclico, metodo para prepararlo y composicion farmaceutica que comprende el mismo.
AU2016296905B2 (en) 2015-07-23 2018-07-05 Centre National De La Recherche Scientifique Use of a combination of Dbait molecule and parp inhibitors to treat cancer
GB201519573D0 (en) 2015-11-05 2015-12-23 King S College London Combination
WO2018162439A1 (en) 2017-03-08 2018-09-13 Onxeo New predictive biomarker for the sensitivity to a treatment of cancer with a dbait molecule
WO2018197461A1 (en) 2017-04-28 2018-11-01 Akribes Biomedical Gmbh A parp inhibitor in combination with a glucocorticoid and/or ascorbic acid and/or a protein growth factor for the treatment of impaired wound healing
CA3092779A1 (en) 2018-03-13 2019-09-19 Onxeo A dbait molecule against acquired resistance in the treatment of cancer
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
CN114437072B (zh) * 2020-10-30 2023-03-31 中国科学院大连化学物理研究所 一种6-甲基异吲哚并[2,1-a]喹喔啉类化合物的合成方法
GB202217888D0 (en) * 2022-11-29 2023-01-11 Duke Street Bio Ltd Pharmaceutical compound
CN121398822A (zh) 2023-06-21 2026-01-23 四方生物科学有限公司 用于在治疗hr功能正常的癌症的方法中的用途的包含脱氧胞苷衍生物和parp抑制剂的组合

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US3594380A (en) * 1969-02-18 1971-07-20 American Home Prod Isoquinolin-1(2h)-ones
EP0355750B1 (en) * 1988-08-19 1995-01-25 Warner-Lambert Company Substituted dihydroisoquinolinones and related compounds as potentiators of the lethal effects of radiation and certain chemotherapeutic agents; selected compounds, analogs and process
CN1278797A (zh) * 1997-09-03 2001-01-03 吉尔福特药品有限公司 氧代化合物、其制备方法和组合物及抑制parp活性的方法

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US3594380A (en) * 1969-02-18 1971-07-20 American Home Prod Isoquinolin-1(2h)-ones
EP0355750B1 (en) * 1988-08-19 1995-01-25 Warner-Lambert Company Substituted dihydroisoquinolinones and related compounds as potentiators of the lethal effects of radiation and certain chemotherapeutic agents; selected compounds, analogs and process
CN1278797A (zh) * 1997-09-03 2001-01-03 吉尔福特药品有限公司 氧代化合物、其制备方法和组合物及抑制parp活性的方法

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James H. Rigby, N. Balasubramanian.Preparation of highly substituted 2-pyridones by reactionof vinyl isocyanates and enamines.The Journal of Organic Chemistry54 1.1989,54(1),224-228. *
James H. Rigby, N. Balasubramanian.Vinyl isocyanate cyclization reactions in synthesis.Anexpedient construction of theoctahydro- phenanthridinonering system.The Journal of Organic Chemistry49 23.1984,49(23),4569-4571. *
James H. Rigby,N.Balasubramanian.Vinyl isocyanate cyclization reactions in synthesis.Anexpedient construction of theoctahydro-phenanthridinonering system.The Journal of Organic Chemistry49 23.1984,49(23),4569-4571. *
James H.Rigby,N.Balasubramanian.Preparation of highly substituted 2-pyridones by reactionof vinyl isocyanates and enamines.The Journal of Organic Chemistry54 1.1989,54(1),224-228. *

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EP1758864A1 (de) 2007-03-07
AU2005254632B2 (en) 2011-09-15
BRPI0512139A (pt) 2008-02-12
CA2570942A1 (en) 2005-12-29
JP2008502614A (ja) 2008-01-31
CA2570942C (en) 2012-12-11
US20110021462A1 (en) 2011-01-27
EP1758864B1 (de) 2013-04-10
MXPA06013876A (es) 2007-03-07
IL179758A (en) 2010-12-30
AU2005254632A1 (en) 2005-12-29
HK1100409A1 (zh) 2007-09-21
JP4928446B2 (ja) 2012-05-09
WO2005123687A1 (de) 2005-12-29
KR20070024612A (ko) 2007-03-02
KR101169919B1 (ko) 2012-08-06
US7795278B2 (en) 2010-09-14
DE102004028973A1 (de) 2006-01-05
CN1968929A (zh) 2007-05-23
IL179758A0 (en) 2007-05-15
US20070142430A1 (en) 2007-06-21

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