CL2012000708A1 - Compuestos derivados de imidazopiridina o imidazopirimidina, inhibidores de pde10a; proceso de preparacion de dichos compuestos; composiciones farmaceuticas; y su uso para el tratamiento terapeutico y/o preventivo de trastornos psicoticos, esquizofrenia, enfermedad de alzheimer, tumores solidos, entre otras enfermedades. - Google Patents

Compuestos derivados de imidazopiridina o imidazopirimidina, inhibidores de pde10a; proceso de preparacion de dichos compuestos; composiciones farmaceuticas; y su uso para el tratamiento terapeutico y/o preventivo de trastornos psicoticos, esquizofrenia, enfermedad de alzheimer, tumores solidos, entre otras enfermedades.

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Publication number
CL2012000708A1
CL2012000708A1 CL2012000708A CL2012000708A CL2012000708A1 CL 2012000708 A1 CL2012000708 A1 CL 2012000708A1 CL 2012000708 A CL2012000708 A CL 2012000708A CL 2012000708 A CL2012000708 A CL 2012000708A CL 2012000708 A1 CL2012000708 A1 CL 2012000708A1
Authority
CL
Chile
Prior art keywords
compounds
imidazopyrimidine
imidazopyridine
schizophrenia
alzheimer
Prior art date
Application number
CL2012000708A
Other languages
English (en)
Inventor
Sanchez Ruben Alvarez
Daniela Alberati
Zbinden Katrin Groebke
Markus Rudolph
Bernd Kuhn
Konrad Bleicher
Alexander Flohr
Matthias Koerner
Jens-Uwe Peters
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of CL2012000708A1 publication Critical patent/CL2012000708A1/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • 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
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • 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
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material 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)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Diabetes (AREA)
  • Psychology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Oncology (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Addiction (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

COMPUESTOS DERIVADOS DE IMIDAZOPIRIDINA O IMIDAZOPIRIMIDINA DE FORMULA (I): EN LOS QUE R1 , R2, R3, R4, R5 Y A SON COMO SE HA DEFINIDO EN LA MEMORIA DESCRIPTIVA Y PLIEGO DE REIVINDICACIONES, ASÍ COMO SALES FISIOLÓGICAMENTE ACEPTABLES DE LOS MISMOS, COMPUESTOS QUE INHIBEN PDE10A, PROCEDIMIENTO DE PREPARACIÓN, COMPOSICIONES FARMACÉUTICAS, Y SU USO PARA EL TRATAMIENTO TERAPÉUTICO Y/O PREVENTIVO DE TRASTORNOS PSICÓTICOS, ESQUIZOFRENIA, ENFERMEDAD DE ALZHEIMER, TUMORES SÓLIDOS, ENTRE OTRAS ENFERMEDADES.<br />  
CL2012000708A 2009-09-24 2012-03-22 Compuestos derivados de imidazopiridina o imidazopirimidina, inhibidores de pde10a; proceso de preparacion de dichos compuestos; composiciones farmaceuticas; y su uso para el tratamiento terapeutico y/o preventivo de trastornos psicoticos, esquizofrenia, enfermedad de alzheimer, tumores solidos, entre otras enfermedades. CL2012000708A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP09171253 2009-09-24

Publications (1)

Publication Number Publication Date
CL2012000708A1 true CL2012000708A1 (es) 2012-09-07

Family

ID=43416552

Family Applications (1)

Application Number Title Priority Date Filing Date
CL2012000708A CL2012000708A1 (es) 2009-09-24 2012-03-22 Compuestos derivados de imidazopiridina o imidazopirimidina, inhibidores de pde10a; proceso de preparacion de dichos compuestos; composiciones farmaceuticas; y su uso para el tratamiento terapeutico y/o preventivo de trastornos psicoticos, esquizofrenia, enfermedad de alzheimer, tumores solidos, entre otras enfermedades.

Country Status (22)

Country Link
US (2) US8017604B2 (es)
EP (1) EP2480546B1 (es)
JP (1) JP5629322B2 (es)
KR (1) KR101426624B1 (es)
CN (1) CN102548991B (es)
AR (1) AR078437A1 (es)
BR (1) BR112012006531A2 (es)
CA (1) CA2770087C (es)
CL (1) CL2012000708A1 (es)
CY (1) CY1116120T1 (es)
DK (1) DK2480546T3 (es)
ES (1) ES2530884T3 (es)
HR (1) HRP20150345T1 (es)
IL (1) IL218032A (es)
MX (1) MX2012003469A (es)
PE (1) PE20121438A1 (es)
PL (1) PL2480546T3 (es)
PT (1) PT2480546E (es)
RU (1) RU2502737C2 (es)
SI (1) SI2480546T1 (es)
TW (1) TWI402268B (es)
WO (1) WO2011036127A1 (es)

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US8470820B2 (en) * 2010-01-22 2013-06-25 Hoffman-La Roche Inc. Nitrogen-containing heteroaryl derivatives
CN103298468A (zh) * 2011-02-01 2013-09-11 协和发酵麒麟株式会社 稠环杂环衍生物
RU2013142364A (ru) 2011-02-18 2015-03-27 Аллерган, Инк. Замещенные производные 6,7-диалкокси-3-изохинолинола в качестве ингибиторов фосфодиэстеразы 10 (фдэ10а)
US8975276B2 (en) * 2011-06-29 2015-03-10 Bristol-Myers Squibb Company Inhibitors of PDE10
EP2574607A1 (en) 2011-09-06 2013-04-03 F. Hoffmann-La Roche AG PDE10 modulators
CA2846758C (en) * 2011-09-19 2017-09-12 F. Hoffmann-La Roche Ag Triazolopyridine compounds as pde10a inhibitors
WO2014071044A1 (en) 2012-11-01 2014-05-08 Allergan, Inc. Substituted 6,7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (pde10a)
KR20150111354A (ko) * 2013-01-31 2015-10-05 에프. 호프만-라 로슈 아게 방사성 표지된 화합물
KR102169426B1 (ko) 2013-02-27 2020-10-23 모찌다 세이야쿠 가부시끼가이샤 신규 피라졸 유도체
RU2015147450A (ru) 2013-04-29 2017-06-05 Ф. Хоффманн-Ля Рош Аг ПРОИЗВОДНЫЕ 2-ФЕНИЛ ИЛИ 2-ГЕТЕРОАРИЛ ИМИДАЗОЛ[1,2-a]ПИРИДИНА
JP2016520047A (ja) * 2013-04-30 2016-07-11 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ ピラゾールアミドのＰｄ触媒カップリング
WO2015006689A1 (en) 2013-07-12 2015-01-15 University Of South Alabama Treatment and diagnosis of cancer and precancerous conditions using pde10a inhibitors and methods to measure pde10a expression
JP6182668B2 (ja) * 2013-09-26 2017-08-16 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ 画像化ツールとしてのイミダゾ［１，２−ａ］ピリジン−７−アミン
US9200016B2 (en) 2013-12-05 2015-12-01 Allergan, Inc. Substituted 6, 7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (PDE 10A)
LT3507291T (lt) 2016-09-02 2021-09-10 Cyclerion Therapeutics, Inc. Kondensuoti bicikliniai sgc stimuliatoriai
CN113698406A (zh) * 2021-08-30 2021-11-26 成都药明康德新药开发有限公司 6-甲基吡唑并[1,5-a]嘧啶-3-胺的合成方法

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US6610697B1 (en) * 1999-11-10 2003-08-26 Ortho-Mcneil Pharmaceutical, Inc. Substituted 2-aryl-3-(heteroaryl)-imidazo[1,2-a]pyrimidines, and related pharmaceutical compositions and methods
SE0102808D0 (sv) * 2001-08-22 2001-08-22 Astrazeneca Ab New compounds
SI1557411T1 (es) * 2002-07-12 2013-01-31 Astellas Pharma Inc
EP1570847B1 (en) * 2002-12-03 2012-04-25 Kyorin Pharmaceutical Co., Ltd. Phosphodiesterase 10a inhibitors for use in the treatment of parkinson's disease, huntington's disease and schizophrenia
EP1651251A4 (en) 2003-07-31 2008-06-18 Bayer Pharmaceuticals Corp METHOD FOR THE TREATMENT OF DIABETES AND RELATED DISEASES USING PDE 10A INHIBITORS
AU2005240942B2 (en) * 2004-05-10 2010-08-05 Banyu Pharmaceutical Co., Ltd. Imidazopyridine compound
EP1853590A1 (en) * 2005-03-03 2007-11-14 Sirtris Pharmaceuticals, Inc. Fused heterocyclic compounds and their use as sirtuin modulators
RU2426732C2 (ru) * 2006-01-17 2011-08-20 Ф. Хоффманн-Ля Рош Аг АРИЛ-ИЗОКСАЗОЛ-4-ИЛ-ИМИДАЗО[1,2-a]ПИРИДИН, ПРИГОДНЫЙ ДЛЯ ЛЕЧЕНИЯ БОЛЕЗНИ АЛЬЦГЕЙМЕРА ЧЕРЕЗ ПОСРЕДСТВО GABA-РЕЦЕПТОРОВ
JP2009527560A (ja) 2006-02-21 2009-07-30 アムゲン インコーポレイティッド ホスホジエステラーゼ１０阻害剤としてのシンノリン誘導体
DE102007012645A1 (de) * 2007-03-16 2008-09-18 Bayer Healthcare Ag Substituierte Imidazo- und Triazolopyrimidine
FR2926556B1 (fr) * 2008-01-22 2010-02-19 Sanofi Aventis Derives de carboxamides n-azabicycliques, leur preparation et leur application en therapeutique

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MX2012003469A (es) 2012-04-19
ES2530884T3 (es) 2015-03-06
RU2502737C2 (ru) 2013-12-27
CA2770087A1 (en) 2011-03-31
AR078437A1 (es) 2011-11-09
EP2480546A1 (en) 2012-08-01
AU2010299927A1 (en) 2012-03-15
TW201116530A (en) 2011-05-16
CA2770087C (en) 2014-09-09
WO2011036127A1 (en) 2011-03-31
KR20120068943A (ko) 2012-06-27
JP5629322B2 (ja) 2014-11-19
CN102548991B (zh) 2015-03-25
HRP20150345T1 (hr) 2015-05-08
BR112012006531A2 (pt) 2016-11-22
PE20121438A1 (es) 2012-10-26
IL218032A (en) 2014-06-30
SI2480546T1 (sl) 2015-03-31
US20110294779A1 (en) 2011-12-01
EP2480546B1 (en) 2014-12-31
KR101426624B1 (ko) 2014-08-05
CN102548991A (zh) 2012-07-04
DK2480546T3 (en) 2015-02-02
US20110071128A1 (en) 2011-03-24
US8263584B2 (en) 2012-09-11
PL2480546T3 (pl) 2015-05-29
IL218032A0 (en) 2012-04-30
PT2480546E (pt) 2015-02-09
CY1116120T1 (el) 2017-02-08
US8017604B2 (en) 2011-09-13
TWI402268B (zh) 2013-07-21
JP2013505911A (ja) 2013-02-21
RU2012113128A (ru) 2013-11-10

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