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ES2377337T3 - Derivados pirimidina y su uso como antogonistas del receptor P2Y12 - Google Patents

Derivados pirimidina y su uso como antogonistas del receptor P2Y12 Download PDF

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Publication number
ES2377337T3
ES2377337T3 ES06728064T ES06728064T ES2377337T3 ES 2377337 T3 ES2377337 T3 ES 2377337T3 ES 06728064 T ES06728064 T ES 06728064T ES 06728064 T ES06728064 T ES 06728064T ES 2377337 T3 ES2377337 T3 ES 2377337T3
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alkyl
hydrogen
aryl
heterocyclic ring
cycloalkyl
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Eva Caroff
Heinz Fretz
Kurt Hilpert
Olivier Houille
Francis Hubler
Emmanuel Meyer
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Actelion Pharmaceuticals Ltd
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Actelion Pharmaceuticals Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • 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
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P9/08Vasodilators 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/34One oxygen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/38One sulfur atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/42One nitrogen atom
    • 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
    • C07D401/04Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/14Heterocyclic 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)

Abstract

Un compuesto seleccionado del grupo que consiste en los compuestos de fórmula I en la cual R1 representa fenilo opcionalmente sustituido de 1 a 3 veces por sustituyentes cada uno independientemente seleccionado del grupo que consiste en halógeno, metilo, metoxi, trifluorometilo y trifluorometoxi; W representa un enlace, y R2 representa alquilo, haloalquilo, ciano, hidroxialquilo, hidroxialquilo sustituido en su cadena alquílica con un grupo fenilo no sustituido, alcoxialquilo, heterociclilo, heterociclilalquilo, cicloalquilo, cicloalquilalquilo, arilo, heteroarilo, o uno de los radicales en los cuales m es 0 y n es 2 ó 3, o m es 1 y n es 2, p es 0 y q es 2 ó 3, o p es 1 y q es 2, o también p es 2 ó 3 y q es 0, Q es -CO- o -CH(ORa)-, siendo Ra hidrógeno o alquilo, y Q' es -CO-; o W representa -CH2- y R2 representa -NR7R8, -SR9 o -SO2R10; W representa -O- o -S- y R2 representa alquilo, carboxialquilo, alcoxicarbonilalquilo, hidroxialquilo, alcoxialquilo, heterociclilalquilo, cicloalquilo, cicloalquilalquilo, arilo, aralquilo, heteroarilo o heteroarilalquilo; W representa -NR3- y R2 representa hidrógeno, alquilo, dialquilaminoalquilo, alcoxicarbonilalquilo, carboxialquilo, carboxialquilo sustituido en su sección alquilo con un grupo fenilo no sustituido, hidroxialquilo, alcoxialquilo, heterociclilo, heterociclilalquilo, cicloalquilo, cicloalquilalquilo, arilo, 2-fenilciclopropilo, aralquilo, difenilalquilo, heteroarilalquilo en donde el heteroarilo es un heteroarilo monocíclico, -COR11 ó -SO2R12; W representa -CH=CH- y R2 representa alquilo, hidroxialquilo, alcoxialquilo, alcoxicarbonilo, fenilo o -CO-NR13R14; o W representa -CºC- y R2 representa hidrógeno, alquilo, hidroxialquilo o alcoxialquilo; o W representa -CO- y R2 representa alquilo; R3 representa hidrógeno o alquilo; R7 representa alquilo o arilalquilo; R8 representa alquilo; o R7 y R8 forman, en conjunto con el nitrógeno que los porta, un anillo heterocíclico de 4 a 7 elementos en el cual los elementos que se necesitan para completar dicho anillo heterocíclico se seleccionan de manera 5 independiente de entre -CH2-, -CH(CH3)-, -CHRy-, -O-, -S-, -CO- y -NRz-, entendiéndose sin embargo que dicho anillo heterocíclico no contiene más que un elemento seleccionado del grupo que consiste en -CHRy-, -O-, -S-, -CO- y -NRz-, representando Ry hidroxi, hidroximetilo, alcoximetilo, alcoxicarbonilo o alcoxi y representando Rz hidrógeno, alquilo o alcoxicarbonilo; R9 representa cicloalquilo o arilo; R10 representa alquilo, cicloalquilo o arilo; R11 representa alquilo, alcoxialquilo, cicloalquilo, cicloalquilalquilo, arilo, heteroarilo monocíclico o aralquilo; R12 representa alquilo o arilo; R13 representa alquilo; R14 representa alquilo; o W representa -NR3- y R2 y R3 forman, en conjunto con el nitrógeno que los porta, un anillo heterocíclico de 4 a 7 elementos en el cual los elementos que se necesitan para completar dicho anillo heterocíclico se seleccionan de manera independiente de entre -CH2-, -CHRx-, -O-, -S-, -CO- y -NR4-, y entendiéndose que dicho anillo heterocíclico no contiene más que un elemento seleccionado del grupo que consiste en -CHRx-, -O-, -S-, -CO- y -NR4-, representando Rx hidroxi, hidroximetilo, alcoximetilo o alcoxi y R4 20 representando hidrógeno o alquilo; o también W representa -NR3- y R2 y R3 forman, en conjunto con el nitrógeno que los porta, bien un anillo imidazolilo, pirazolilo, 1,2,3-triazolilo o 1,2,4-triazolilo, anillo que puede estar sustituido con un grupo alquilo, o un anillo 4-oxo-4H-piridin-1-ilo, 4,5-dihidro-pirazol-1-ilo, 2-metil-4,5-dihidro-imidazol-1-ilo o 3-metil-5-oxo-2,5- dihidro-pirazol-1-ilo; cada uno de R5a y R5b representa, de manera independiente, hidrógeno o metilo; X representa -CO- y R6 representa alquilo, cicloalquilo, alcoxi, alquiniloxi, ariloxi, aralcoxi, arilo, heteroarilo monocíclico, aralquilo o NR15R16, o X representa -SO2- y R6 representa alquilo; R15 representa alquilo; R16 representa hidrógeno o alquilo; o R15 y R16 forman, en conjunto con el nitrógeno que los porta, un anillo heterocíclico de 4 a 7 elementos, en el cual los elementos que se necesitan para completar dicho anillo heterocíclico se seleccionan de manera independiente de entre -CH2-, -O-, -S- y -NRw-, representando Rw hidrógeno o alquilo, entendiéndose que dicho anillo heterocíclico no contiene más que un elemento del grupo que consiste en -O-, -S- y -NRw-; e Y representa un enlace y Z representa hidrógeno o arilo sustituido por carboxialcoxi; o Y representa alquileno, alcoxialquileno, fenilalquileno, alcoxifenileno o alcoxifenilalquileno y Z representa hidrógeno, -OH, -NH2, -COOH, tetrazolilo, -CO-NH2, -COOR17, -NH-CO-R17, -NH-COOR17 o -NH-SO2-R17, representando R17 alquilo; y un enantiómero ópticamente puro, una mezcla de enantiómeros, un racemato, un diastereoisómero ópticamente puro, una mezcla de diastereoisómeros, un racemato diastereoisomérico, una mezcla de racematos diastereoisoméricos, una meso forma, una sal, un complejo disuelto, o una forma morfológica del mismo.
ES06728064T 2005-04-28 2006-04-27 Derivados pirimidina y su uso como antogonistas del receptor P2Y12 Active ES2377337T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP2005004578 2005-04-28
WOPCT/EP2005/004578 2005-04-28
IB2005053711 2005-11-10
WOPCT/IB2005/053711 2005-11-10
PCT/IB2006/051318 WO2006114774A2 (en) 2005-04-28 2006-04-27 Pyrimidine derivatives and their use as p2y12 receptor antagonists

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US (1) US8048881B2 (es)
EP (1) EP1893634B1 (es)
JP (1) JP4955658B2 (es)
KR (1) KR101310016B1 (es)
CN (1) CN101166756A (es)
AR (1) AR056992A1 (es)
AT (1) ATE538130T1 (es)
AU (1) AU2006241260A1 (es)
BR (1) BRPI0608089A2 (es)
CA (1) CA2604967C (es)
ES (1) ES2377337T3 (es)
IL (1) IL186939A0 (es)
MX (1) MX2007013436A (es)
NO (1) NO20076094L (es)
NZ (1) NZ563584A (es)
RU (1) RU2410393C2 (es)
TW (1) TW200640877A (es)
WO (1) WO2006114774A2 (es)

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JP2009534310A (ja) * 2006-03-29 2009-09-24 武田薬品工業株式会社 レニン阻害剤
AR063258A1 (es) 2006-10-13 2009-01-14 Actelion Pharmaceuticals Ltd Derivados de 2-aminocarbonil-piridina, una composicion farmaceutica que los contiene y su uso en la preparacion de un medicamento para el tratamiento de trastornos vasculares oclusivos.
AR063518A1 (es) * 2006-10-25 2009-01-28 Actelion Pharmaceuticals Ltd Derivados 2-fenil-6-aminocarbonil-pirimidina; composicion farmaceutica; y su uso para tratar y/o prevenir enfermedades vasculares perifericas viscerales, hepaticas y renales, enfermedades cardiovasculares y enfermedades cerebrovasculares asociados con la agregacion de plaquetas, incluyendo trombosis
KR20100015886A (ko) 2007-04-23 2010-02-12 사노피-아벤티스 P2y12 길항제로서의 퀴놀린-카복스아미드 유도체
TWI361690B (en) * 2007-11-29 2012-04-11 Actelion Pharmaceuticals Ltd Phosphonic acid derivatives
JP5504171B2 (ja) * 2007-12-26 2014-05-28 サノフイ P2y12アンタゴニストとしてのヘテロサイクリックピラゾール−カルボキサミド
JP5560202B2 (ja) * 2007-12-26 2014-07-23 サノフイ P2y12拮抗薬としてのピラゾール−カルボキサミド誘導体
EP2262766B1 (en) 2008-02-29 2015-11-11 Evotec AG Amide compounds, compositions and uses thereof
AR071653A1 (es) * 2008-04-11 2010-07-07 Actelion Pharmaceuticals Ltd Derivados 2-fenil-4-ciclopropil-pirimidina
AR071652A1 (es) * 2008-04-11 2010-07-07 Actelion Pharmaceuticals Ltd Derivados 2- fenil-piridina substituidos
EP2284159A4 (en) * 2008-04-22 2012-06-13 Daiichi Sankyo Co Ltd 5-hydroxypyrimidine-4-carboxamide compound
US20110237578A1 (en) 2008-09-18 2011-09-29 Zhi-Liang Wei Amide compounds, compositions and uses thereof
KR101114503B1 (ko) * 2008-12-04 2012-02-15 지에스건설 주식회사 부유물 수거장치
WO2010116328A2 (en) * 2009-04-08 2010-10-14 Actelion Pharmaceuticals Ltd 6-(3-aza-bicyclo[3.1.0]hex-3-yl)-2-phenyl-pyrimidines
EP2421859B1 (en) * 2009-04-22 2014-04-09 Actelion Pharmaceuticals Ltd. Thiazole derivatives and their use as p2y12 receptor antagonists
JP5597202B2 (ja) 2009-08-28 2014-10-01 第一三共株式会社 3−(ビアリールオキシ)プロピオン酸誘導体
WO2013033178A1 (en) 2011-08-30 2013-03-07 University Of Utah Research Foundation Methods and compositions for treating nephrogenic diabetes insipidus
EP2753606B1 (en) * 2011-09-02 2017-07-05 Purdue Pharma LP Pyrimidines as sodium channel blockers
HUE057772T2 (hu) 2016-09-22 2022-06-28 Idorsia Pharmaceuticals Ltd Kristályos formák
KR102510832B1 (ko) 2017-03-15 2023-03-15 이도르시아 파마슈티컬스 리미티드 P2y12 수용체 안타고니스트의 피하 투여
CN112500354A (zh) * 2020-12-08 2021-03-16 烟台凯博医药科技有限公司 一种4-氯-6-环丙基嘧啶-5-胺的合成方法
WO2025133948A1 (en) 2023-12-21 2025-06-26 Pfizer Inc. Acetyl coa-carboxylase (acc) inhibitors

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AR063258A1 (es) 2006-10-13 2009-01-14 Actelion Pharmaceuticals Ltd Derivados de 2-aminocarbonil-piridina, una composicion farmaceutica que los contiene y su uso en la preparacion de un medicamento para el tratamiento de trastornos vasculares oclusivos.
AR063518A1 (es) 2006-10-25 2009-01-28 Actelion Pharmaceuticals Ltd Derivados 2-fenil-6-aminocarbonil-pirimidina; composicion farmaceutica; y su uso para tratar y/o prevenir enfermedades vasculares perifericas viscerales, hepaticas y renales, enfermedades cardiovasculares y enfermedades cerebrovasculares asociados con la agregacion de plaquetas, incluyendo trombosis
TWI361690B (en) 2007-11-29 2012-04-11 Actelion Pharmaceuticals Ltd Phosphonic acid derivatives
AR071652A1 (es) 2008-04-11 2010-07-07 Actelion Pharmaceuticals Ltd Derivados 2- fenil-piridina substituidos
AR071653A1 (es) 2008-04-11 2010-07-07 Actelion Pharmaceuticals Ltd Derivados 2-fenil-4-ciclopropil-pirimidina
WO2010116328A2 (en) 2009-04-08 2010-10-14 Actelion Pharmaceuticals Ltd 6-(3-aza-bicyclo[3.1.0]hex-3-yl)-2-phenyl-pyrimidines
EP2421859B1 (en) 2009-04-22 2014-04-09 Actelion Pharmaceuticals Ltd. Thiazole derivatives and their use as p2y12 receptor antagonists

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Publication number Publication date
US8048881B2 (en) 2011-11-01
US20080194576A1 (en) 2008-08-14
CN101166756A (zh) 2008-04-23
BRPI0608089A2 (pt) 2009-11-10
KR20080004608A (ko) 2008-01-09
AU2006241260A1 (en) 2006-11-02
RU2007143880A (ru) 2009-06-10
AR056992A1 (es) 2007-11-07
CA2604967C (en) 2014-04-01
IL186939A0 (en) 2008-02-09
RU2410393C2 (ru) 2011-01-27
CA2604967A1 (en) 2006-11-02
MX2007013436A (es) 2008-01-16
JP4955658B2 (ja) 2012-06-20
KR101310016B1 (ko) 2013-09-30
NO20076094L (no) 2008-01-25
ATE538130T1 (de) 2012-01-15
NZ563584A (en) 2011-03-31
EP1893634A2 (en) 2008-03-05
JP2008539224A (ja) 2008-11-13
EP1893634B1 (en) 2011-12-21
WO2006114774A2 (en) 2006-11-02
WO2006114774A3 (en) 2007-02-08
TW200640877A (en) 2006-12-01

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