TW201617348A - 化合物 - Google Patents

化合物 Download PDF

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Publication number
TW201617348A
TW201617348A TW104123494A TW104123494A TW201617348A TW 201617348 A TW201617348 A TW 201617348A TW 104123494 A TW104123494 A TW 104123494A TW 104123494 A TW104123494 A TW 104123494A TW 201617348 A TW201617348 A TW 201617348A
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TW
Taiwan
Prior art keywords
disease
compound
pharmaceutically acceptable
treatment
oxy
Prior art date
Application number
TW104123494A
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English (en)
Chinese (zh)
Inventor
澤紅 萬
章曉明
王劍
Original Assignee
葛蘭素史克智慧財產發展有限公司
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Publication of TW201617348A publication Critical patent/TW201617348A/zh

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    • 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
    • C07D487/12—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 three hetero rings
    • C07D487/14—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
    • A61K31/495—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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P17/06—Antipsoriatics
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A61P25/28—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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • 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
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—Ortho-condensed systems
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/20—Spiro-condensed systems
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
    • C07D491/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
    • C07D513/14—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Psychiatry (AREA)
  • Dermatology (AREA)
  • Endocrinology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Emergency Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Ophthalmology & Optometry (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
TW104123494A 2014-07-22 2015-07-21 化合物 TW201617348A (zh)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN2014000695 2014-07-22

Publications (1)

Publication Number Publication Date
TW201617348A true TW201617348A (zh) 2016-05-16

Family

ID=55162512

Family Applications (1)

Application Number Title Priority Date Filing Date
TW104123494A TW201617348A (zh) 2014-07-22 2015-07-21 化合物

Country Status (14)

Country Link
US (5) US9783546B2 (index.php)
EP (2) EP3172208B1 (index.php)
JP (2) JP6625603B2 (index.php)
KR (2) KR20170034889A (index.php)
CN (2) CN106536521B (index.php)
AR (1) AR101261A1 (index.php)
AU (2) AU2015292048B2 (index.php)
BR (1) BR112016030939B1 (index.php)
CA (2) CA2970537C (index.php)
ES (2) ES2744339T3 (index.php)
RU (2) RU2690190C2 (index.php)
TW (1) TW201617348A (index.php)
UY (1) UY36224A (index.php)
WO (2) WO2016011931A1 (index.php)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9783546B2 (en) * 2014-07-22 2017-10-10 Glaxosmithkline Intellectual Property Development Limited Compounds
US11273176B2 (en) 2016-03-02 2022-03-15 The Brigham And Women's Hospital, Inc. Use of PLA2G5-deficient suppressive macrophages in suppression of inflammation
WO2019063634A1 (en) * 2017-09-26 2019-04-04 INSERM (Institut National de la Santé et de la Recherche Médicale) DARAPLADIB RADIOMARQUÉ, ITS ANALOGUES AND THEIR USE AS IMAGING COMPOUNDS
CN109988126B (zh) * 2017-12-29 2023-05-16 南京富润凯德生物医药有限公司 一种3-氨基-氧杂环丁烷衍生物及其制备方法和应用
CN109134523A (zh) * 2018-09-30 2019-01-04 中昊(大连)化工研究设计院有限公司 一种3，6-二氢-2h-吡喃-4-硼酸频哪醇酯的合成新工艺
JP2022116370A (ja) * 2019-06-13 2022-08-10 アグロカネショウ株式会社 新規な１－ベンジルアミン誘導体及びこれを有効成分とする農園芸用薬剤
CN112574221B (zh) * 2019-09-30 2022-03-04 上海纽思克生物科技有限公司 四环嘧啶酮类化合物、其制备方法、其组合物和用途
CN114805389B (zh) * 2019-11-09 2023-08-29 上海赛默罗生物科技有限公司 三环二氢咪唑并嘧啶酮衍生物、其制备方法、药物组合物和用途
EP4151638A4 (en) * 2020-05-13 2024-06-12 Neusco Biotech Limited BRIDGED CYCLIC PYRIMIDINONE COMPOUND, METHOD FOR PREPARING IT, COMPOSITION CONTAINING IT AND ITS USE
CN113666930B (zh) * 2020-05-13 2022-10-25 上海纽思克生物科技有限公司 桥环嘧啶酮类化合物、其制备方法、其组合物和用途
CN113861220B (zh) * 2020-06-30 2023-06-16 上海纽思克生物科技有限公司 三环嘧啶酮类化合物、其制备方法、其组合物和用途
CN113912622B (zh) * 2020-07-10 2023-12-01 上海纽思克生物科技有限公司 三环嘧啶酮类化合物、其制备方法、其组合物和用途
CN115304620A (zh) 2021-05-07 2022-11-08 上海赛默罗生物科技有限公司 嘧啶酮衍生物、其制备方法、药物组合物和用途
CN114057740B (zh) * 2021-12-15 2024-04-02 上海赛默罗生物科技有限公司 螺环嘧啶酮衍生物、其制备方法、药物组合物和用途
US20250154153A1 (en) * 2022-08-04 2025-05-15 4B Technologies (Beijing) Co., Limited Dihydroimidazo-pyrimidinone compounds as lp-pla2 inhibitors and use thereof
EP4698181A2 (en) * 2023-04-18 2026-02-25 SciNeuro Therapeutics Inc. Combination therapy with lp-pla2 inhibitor and a second agent
AU2024291740A1 (en) * 2023-07-17 2026-02-19 Jiangsu Nhwa Pharmaceutical Co., Ltd Bicyclo[5,6] imidazole pyrimidone derivative and preparation method therefor and use thereof
WO2025217646A1 (en) * 2024-04-12 2025-10-16 Scineuro Therapeutics Inc. Method of treating neurodegenerative and ocular neovascular diseases

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GB0127143D0 (en) 2001-11-10 2002-01-02 Smithkline Beecham Novel compounds
AU2003250470A1 (en) * 2002-08-13 2004-02-25 Warner-Lambert Company Llc Pyrimidinone fused bicyclic metalloproteinase inhibitors
GB0320522D0 (en) 2003-09-02 2003-10-01 Glaxo Group Ltd Formulation
WO2009147476A1 (en) 2008-06-02 2009-12-10 Matrix Laboratories Ltd. Novel pde inhibitors, pharmaceutical compositions containing them and processes for their preparation
US8871928B2 (en) * 2010-09-20 2014-10-28 Glaxo Group Limited Tricyclic compounds, preparation methods, and their uses
ES2847883T3 (es) * 2010-12-17 2021-08-04 Glaxo Group Ltd Uso de inhibidores de LP-PLA2 en el tratamiento y prevención de enfermedades oculares
AU2012253615B2 (en) * 2011-05-09 2017-03-02 Eip Pharma, Llc Compositions and methods for treating Alzheimer's disease
CN103827118B (zh) 2011-07-27 2016-03-09 葛兰素集团有限公司 双环嘧啶酮化合物
BR112014001665A2 (pt) * 2011-07-27 2017-02-14 Glaxo Group Ltd compostos de 2,3-di-hidroimidazo[1,2-c]pirimidin-5(1h)-ona utilizados como inibidores de lp-plaz
BR112014001634A2 (pt) * 2011-07-27 2017-02-14 Glaxo Group Ltd compostos bicíclicos de pirimidona
CN104024249A (zh) 2011-10-17 2014-09-03 埃南塔制药公司 丙型肝炎病毒抑制剂
JP6065786B2 (ja) 2012-09-14 2017-01-25 信越化学工業株式会社 化学増幅レジスト材料及びパターン形成方法
US20150344485A1 (en) 2013-01-25 2015-12-03 Glaxosmithkline Intellectual Property Development Limited Bicyclic pyrimidone compounds as inhibitors of lp-pla2
CA2899091A1 (en) * 2013-01-25 2014-07-31 Glaxosmithkline Intellectual Property Development Limited Compounds
CN103927116A (zh) 2014-03-18 2014-07-16 兴唐通信科技有限公司 基于触屏设备的手势输入汉字的键盘和方法
US9783546B2 (en) 2014-07-22 2017-10-10 Glaxosmithkline Intellectual Property Development Limited Compounds

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CN106536521B (zh) 2018-08-03
KR20170034889A (ko) 2017-03-29
RU2017105476A3 (index.php) 2019-02-28
RU2017105353A3 (index.php) 2018-11-26
AU2015292048A1 (en) 2016-12-15
US20170204109A1 (en) 2017-07-20
BR112016030939A2 (index.php) 2017-08-22
RU2017105476A (ru) 2018-08-28
CN106536525B (zh) 2019-05-03
BR112016030939B1 (pt) 2023-10-24
CN106536521A (zh) 2017-03-22
WO2016011931A1 (en) 2016-01-28
RU2690190C2 (ru) 2019-05-31
US20240300965A1 (en) 2024-09-12
US10125141B2 (en) 2018-11-13
ES2747636T3 (es) 2020-03-11
EP3172208A4 (en) 2017-12-06
ES2744339T3 (es) 2020-02-24
AU2015292049A1 (en) 2016-12-15
CN106536525A (zh) 2017-03-22
US20200055863A1 (en) 2020-02-20
RU2017105353A (ru) 2018-08-22
JP6625603B2 (ja) 2019-12-25
US11999746B2 (en) 2024-06-04
JP6625604B2 (ja) 2019-12-25
EP3172211A1 (en) 2017-05-31
JP2017520613A (ja) 2017-07-27
US10428078B2 (en) 2019-10-01
US20170204108A1 (en) 2017-07-20
CA2970537C (en) 2023-02-21
US9783546B2 (en) 2017-10-10
AU2015292048B2 (en) 2017-06-29
AU2015292049B2 (en) 2017-06-15
WO2016011930A1 (en) 2016-01-28
EP3172208A1 (en) 2017-05-31
AR101261A1 (es) 2016-12-07
EP3172208B1 (en) 2019-06-12
KR20170029516A (ko) 2017-03-15
CA2955910C (en) 2022-07-12
CA2970537A1 (en) 2016-01-28
JP2017521456A (ja) 2017-08-03
US20190023715A1 (en) 2019-01-24
UY36224A (es) 2016-01-29
EP3172211B1 (en) 2019-07-03
CA2955910A1 (en) 2016-01-28
BR112016028591A2 (pt) 2017-08-22
EP3172211A4 (en) 2018-02-14

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