CN102892766B - 激酶抑制剂和用其治疗癌症的方法 - Google Patents

激酶抑制剂和用其治疗癌症的方法 Download PDF

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Publication number
CN102892766B
CN102892766B CN201180018148.2A CN201180018148A CN102892766B CN 102892766 B CN102892766 B CN 102892766B CN 201180018148 A CN201180018148 A CN 201180018148A CN 102892766 B CN102892766 B CN 102892766B
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mmol
title compound
indazol
cyclopropane
indoline
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CN102892766A (zh
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P·B·桑普森
刘勇
李诗韵
B·T·福利斯特
H·W·保尔斯
L·G·爱德华兹
M·费赫
N·K·B·帕特尔
R·劳弗
潘国华
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University Health Network
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/10—Heterocyclic 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 linked by a carbon chain containing aromatic 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • 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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/04—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • 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
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201180018148.2A 2010-04-06 2011-04-06 激酶抑制剂和用其治疗癌症的方法 Active CN102892766B (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US32132910P 2010-04-06 2010-04-06
US32133210P 2010-04-06 2010-04-06
US61/321,329 2010-04-06
US61/321,332 2010-04-06
PCT/CA2010/000518 WO2010115279A1 (en) 2009-04-06 2010-04-06 Kinase inhibitors and method of treating cancer with same
CAPCT/CA2010/000518 2010-04-06
PCT/CA2011/000386 WO2011123946A1 (en) 2010-04-06 2011-04-06 Kinase inhibitors and method of treating cancer with same

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CN102892766B true CN102892766B (zh) 2015-05-20

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Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011506494A (ja) 2007-12-21 2011-03-03 ユニバーシティ・ヘルス・ネットワーク 癌の治療に有用なキナーゼ阻害剤としてのインダゾリル、ベンズイミダゾリル、ベンゾトリアゾリル置換インドルモン誘導体
US8481525B2 (en) 2009-04-06 2013-07-09 University Of Health Network Kinase inhibitors and method of treating cancer with same
EA023173B1 (ru) * 2010-04-06 2016-04-29 Юниверсити Хелс Нетворк Ингибиторы киназы и способ лечения злокачественной опухоли с их помощью
US8933070B2 (en) 2010-07-02 2015-01-13 University Health Network Methods of targeting PTEN mutant diseases and compositions therefor
WO2012048411A1 (en) * 2010-10-13 2012-04-19 University Health Network Plk-4 inhibitors and method of treating cancer with same
EP3444238B1 (en) * 2012-07-27 2021-12-08 Sato Pharmaceutical Co., Ltd. Process for preparing difluoromethylene compounds
EP3057593B1 (en) 2013-10-18 2021-12-08 University Health Network Treatment for pancreatic cancer
KR20160070106A (ko) * 2013-10-18 2016-06-17 유니버시티 헬스 네트워크 Plk-4 억제제의 염 및 결정체들
CN104130175A (zh) * 2014-06-13 2014-11-05 天津科技大学 不同位置取代吲哚酮类衍生物及其应用
US11608334B2 (en) 2017-02-08 2023-03-21 The National Institutes of Pharmaceutical R&D Co., Ltd. Pyrrolo-aromatic heterocyclic compound, preparation method therefor, and medical use thereof
CN108947970B (zh) * 2017-05-18 2022-04-05 四川大学 吲唑类衍生物及其制备方法和用途
AU2018328773B2 (en) 2017-09-08 2023-11-16 University Health Network Combination therapies for inhibition of Polo-like Kinase 4
WO2020097400A1 (en) 2018-11-07 2020-05-14 Dana-Farber Cancer Institute, Inc. Imidazopyridine derivatives and aza-imidazopyridine derivatives as janus kinase 2 inhibitors and uses thereof
US12522583B2 (en) 2018-11-07 2026-01-13 Dana-Farber Cancer Institute, Inc. Benzimidazole derivatives and aza-benzimidazole derivatives as Janus kinase 2 inhibitors and uses thereof
US12415816B2 (en) 2018-11-07 2025-09-16 Dana-Farber Cancer Institute, Inc. Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof
SG11202111003UA (en) 2019-04-24 2021-11-29 Univ Health Network Crystal form s4 of the plk4 inhibitor (1r,2s)-(e)-2-(3-(4-((cis-2,6-dimethylmorpholino)methyl)styryl)- 1 h-imidazol-6- yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one fumarate
KR20220124177A (ko) * 2019-12-06 2022-09-13 유니버시티 헬스 네트워크 급성 골수성 백혈병 또는 골수형성이상증후군의 치료방법
TW202204350A (zh) 2020-05-06 2022-02-01 美商雅捷可斯治療公司 作為ｊａｋ２抑制劑之６－雜芳基氧基苯并咪唑及氮雜苯并咪唑
CN112250614B (zh) 2020-10-20 2022-02-01 苏州大学 3-螺三元环吲哚酮衍生物的合成方法
US12043632B2 (en) 2020-12-23 2024-07-23 Ajax Therapeutics, Inc. 6-heteroaryloxy benzimidazoles and azabenzimidazoles as JAK2 inhibitors
TW202300485A (zh) * 2021-03-02 2023-01-01 大陸商上海齊魯製藥研究中心有限公司 Plk4抑制劑及其用途
CN117794529B (zh) 2021-05-11 2025-02-11 欧瑞克制药公司 Polo样激酶4抑制剂
CN115677682B (zh) * 2021-07-30 2023-07-18 上海齐鲁制药研究中心有限公司 螺环类plk4抑制剂及其用途
WO2023086320A1 (en) 2021-11-09 2023-05-19 Ajax Therapeutics, Inc. Forms and compositions of inhibitors of jak2
CA3234638A1 (en) 2021-11-09 2023-05-19 Ajax Therapeutics, Inc. 6-heteroaryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors
WO2024006379A1 (en) * 2022-06-30 2024-01-04 Axonis Therapeutics, Inc. Methods and compounds for inhibiting mkk7 enzymes
AU2024249981A1 (en) 2023-04-06 2025-10-16 Pfizer Inc. Substituted indazole propionic acid derivative compounds and uses thereof as ampk activators

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2709536A1 (en) * 2007-12-21 2009-07-02 University Health Network Indazolyl, benzimidazolyl, benzotriazolyl substituted indolinone derivatives as kinase inhibitors useful in the treatment of cancer
WO2010115279A1 (en) * 2009-04-06 2010-10-14 University Health Network Kinase inhibitors and method of treating cancer with same

Family Cites Families (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3310891A1 (de) 1983-03-25 1984-09-27 Boehringer Mannheim Gmbh, 6800 Mannheim Neue indolinon-(2)-derivate, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und zwischenprodukte
US5182397A (en) * 1990-05-31 1993-01-26 American Cyanamid Company Aryloxyspiroalkylindolinone herbicides
GB9507298D0 (en) 1995-04-07 1995-05-31 Pharmacia Spa Substituted indolylmethylene-oxindale analogues as tyrosine kinase inhibitors
US5880141A (en) 1995-06-07 1999-03-09 Sugen, Inc. Benzylidene-Z-indoline compounds for the treatment of disease
AU4155697A (en) 1996-08-23 1998-03-06 Sugen, Inc. Indolinone combinatorial libraries and related products and methods for the treatment of disease
GB9716557D0 (en) 1997-08-06 1997-10-08 Glaxo Group Ltd Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity
US6133305A (en) * 1997-09-26 2000-10-17 Sugen, Inc. 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity
AU5468499A (en) 1998-08-04 2000-02-28 Sugen, Inc. 3-methylidenyl-2-indolinone modulators of protein kinase
AU3770000A (en) 1999-03-24 2000-10-09 Sugen, Inc. Indolinone compounds as kinase inhibitors
YU54202A (sh) 2000-01-18 2006-01-16 Agouron Pharmaceuticals Inc. Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije
CA2410509A1 (en) 2000-06-02 2001-12-13 Sugen, Inc. Indolinone derivatives as protein kinase/phosphatase inhibitors
US6897231B2 (en) * 2000-07-31 2005-05-24 Signal Pharmaceuticals, Inc. Indazole derivatives as JNK inhibitors and compositions and methods related thereto
CN1656079A (zh) 2002-05-31 2005-08-17 卫材株式会社 吡唑化合物和含有该化合物的药物组合物
US7148249B2 (en) 2002-09-12 2006-12-12 Boehringer Ingelheim Pharma Gmbh & Co. Kg Indolinones substituted by heterocycles, the preparation thereof and their use as medicaments
WO2004037247A1 (en) * 2002-10-21 2004-05-06 Irm Llc Oxindoles with anti-hiv activity
WO2005058309A1 (en) 2003-12-16 2005-06-30 Leo Pharma A/S Novel therapeutic use of indolinone derivatives
US20050211590A1 (en) 2004-03-26 2005-09-29 Mcclure George K Protective cover for medical devices
DE102005005395A1 (de) 2005-02-03 2006-08-10 Schering Aktiengesellschaft Thiazolidinone, deren Herstellung und Verwendung als Arzneimittel
US7309787B2 (en) * 2005-07-13 2007-12-18 Allergan, Inc. Kinase inhibitors
WO2007058626A1 (en) * 2005-11-16 2007-05-24 S*Bio Pte Ltd Indazole compounds
US20070135509A1 (en) 2005-12-09 2007-06-14 Blackburn Thomas P Indolone compounds useful to treat cognitive impairment
FR2896503B1 (fr) 2006-01-23 2012-07-13 Aventis Pharma Sa Nouveaux derives soufres d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases
WO2007109026A2 (en) 2006-03-15 2007-09-27 The Trustees Of Columbia University In The City Of New York Pten compositions and methods for detecting breast cancer
GB0606234D0 (en) 2006-03-29 2006-05-10 Pliva Istrazivanje I Razvoj D Pharmaceutically acceptable salts and polymorphic forms
JP5551066B2 (ja) * 2007-06-12 2014-07-16 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規化合物
CN103122001A (zh) 2007-09-25 2013-05-29 武田药品工业株式会社 Polo样激酶抑制剂
WO2009065232A1 (en) 2007-11-20 2009-05-28 University Health Network Cancer diagnostic and therapeutic methods that target plk4/sak
JP2009173629A (ja) * 2007-12-21 2009-08-06 Banyu Pharmaceut Co Ltd Ｒｓｋ１阻害作用を有する新規スピロインダン誘導体
CA2717904C (en) * 2008-03-11 2016-08-30 University Health Network Method of treating cancer using a neuropeptide y 5r (np y5r) antagonist
EP2108641A1 (en) * 2008-04-11 2009-10-14 Laboratorios Almirall, S.A. New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors
EP2113503A1 (en) * 2008-04-28 2009-11-04 Laboratorios Almirall, S.A. New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors
WO2010008731A1 (en) 2008-06-16 2010-01-21 Tigris Pharmaceuticals, Inc. Methods for determining sensitivity to aminoflavones
DE102008040187A1 (de) 2008-07-04 2010-01-07 Robert Bosch Gmbh Sensorelement, Verfahren zu seiner Herstellung sowie Verwendung
WO2010017047A1 (en) 2008-08-05 2010-02-11 Merck & Co., Inc. Therapeutic compounds
WO2011069298A1 (en) 2009-12-11 2011-06-16 F. Hoffmann-La Roche Ag Novel cyclopropane indolinone derivatives
JP5056876B2 (ja) 2010-03-19 2012-10-24 Ｊｆｅスチール株式会社 冷間加工性と焼入れ性に優れた熱延鋼板およびその製造方法
EA023173B1 (ru) 2010-04-06 2016-04-29 Юниверсити Хелс Нетворк Ингибиторы киназы и способ лечения злокачественной опухоли с их помощью
US8933070B2 (en) 2010-07-02 2015-01-13 University Health Network Methods of targeting PTEN mutant diseases and compositions therefor
WO2012048411A1 (en) 2010-10-13 2012-04-19 University Health Network Plk-4 inhibitors and method of treating cancer with same
EA024026B1 (ru) 2010-11-25 2016-08-31 Рациофарм Гмбх Новые соли и полиморфные формы афатиниба
EP3323820B1 (en) * 2011-02-28 2023-05-10 Epizyme, Inc. Substituted 6,5-fused bicyclic heteroaryl compounds
GB201109966D0 (en) 2011-06-10 2011-07-27 Cancer Res Inst Royal Materials and methods for treating pten mutated or deficient cancer
WO2013053051A1 (en) 2011-10-12 2013-04-18 University Health Network Indazole compounds as kinase inhibitors and method of treating cancer with same
EP3057593B1 (en) 2013-10-18 2021-12-08 University Health Network Treatment for pancreatic cancer
KR20160070106A (ko) 2013-10-18 2016-06-17 유니버시티 헬스 네트워크 Plk-4 억제제의 염 및 결정체들

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2709536A1 (en) * 2007-12-21 2009-07-02 University Health Network Indazolyl, benzimidazolyl, benzotriazolyl substituted indolinone derivatives as kinase inhibitors useful in the treatment of cancer
WO2010115279A1 (en) * 2009-04-06 2010-10-14 University Health Network Kinase inhibitors and method of treating cancer with same

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MX2012011516A (es) 2013-03-08
US20150133677A1 (en) 2015-05-14
JP5442906B2 (ja) 2014-03-19
EA201270752A1 (ru) 2013-04-30
SI2556071T1 (sl) 2016-12-30
US20170226088A1 (en) 2017-08-10
WO2011123946A8 (en) 2011-12-08
US10077255B2 (en) 2018-09-18
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