CA2970537C - Tricyclic imidazo-pyrimidinone compounds for the mediation of lipoprotein-associated phospholipase a2 - Google Patents

Tricyclic imidazo-pyrimidinone compounds for the mediation of lipoprotein-associated phospholipase a2 Download PDF

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Publication number
CA2970537C
CA2970537C CA2970537A CA2970537A CA2970537C CA 2970537 C CA2970537 C CA 2970537C CA 2970537 A CA2970537 A CA 2970537A CA 2970537 A CA2970537 A CA 2970537A CA 2970537 C CA2970537 C CA 2970537C
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independently
compound
mmol
imidazo
optionally substituted
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CA2970537A1 (en
Inventor
Zehong Wan
Xiaomin Zhang
Jian Wang
Matthew Robert SENDER
Eric Steven Manas
Raphael Anthony RIVERO
Joseph E. Pero
Christopher Ernst NEIPP
Vipulkumar Kantibhai Patel
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GlaxoSmithKline Intellectual Property Development Ltd
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    • 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
    • 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
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (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)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Obesity (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Psychology (AREA)
  • Endocrinology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Vascular Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Ophthalmology & Optometry (AREA)
  • Immunology (AREA)
  • Emergency Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CA2970537A 2014-07-22 2015-07-21 Tricyclic imidazo-pyrimidinone compounds for the mediation of lipoprotein-associated phospholipase a2 Active CA2970537C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2014000695 2014-07-22
CNPCT/CN2014/000695 2014-07-22
PCT/CN2015/084606 WO2016011930A1 (en) 2014-07-22 2015-07-21 Compounds

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Publication Number Publication Date
CA2970537A1 CA2970537A1 (en) 2016-01-28
CA2970537C true CA2970537C (en) 2023-02-21

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CA2970537A Active CA2970537C (en) 2014-07-22 2015-07-21 Tricyclic imidazo-pyrimidinone compounds for the mediation of lipoprotein-associated phospholipase a2
CA2955910A Active CA2955910C (en) 2014-07-22 2015-07-21 Tricyclic imidazo-pyrimidinone compounds as lp-pla2 inhibitors

Family Applications After (1)

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CA2955910A Active CA2955910C (en) 2014-07-22 2015-07-21 Tricyclic imidazo-pyrimidinone compounds as lp-pla2 inhibitors

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US (5) US9783546B2 (enExample)
EP (2) EP3172211B1 (enExample)
JP (2) JP6625603B2 (enExample)
KR (2) KR20170029516A (enExample)
CN (2) CN106536521B (enExample)
AR (1) AR101261A1 (enExample)
AU (2) AU2015292049B2 (enExample)
BR (1) BR112016030939B1 (enExample)
CA (2) CA2970537C (enExample)
ES (2) ES2744339T3 (enExample)
RU (2) RU2017105476A (enExample)
TW (1) TW201617348A (enExample)
UY (1) UY36224A (enExample)
WO (2) WO2016011931A1 (enExample)

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EP3172211B1 (en) 2014-07-22 2019-07-03 GlaxoSmithKline Intellectual Property Development Limited Tricyclic imidazo-pyrimidinone derivatives for the treatment of diseases mediated by lp-pla2
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
ES2907130T3 (es) * 2017-09-26 2022-04-22 Inst Nat Sante Rech Med Darapladib radiomarcado, análogos del mismo y su uso como compuestos para la obtención de imágenes
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
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
JP7595964B2 (ja) * 2020-05-13 2024-12-09 上海紐思克生物科技有限公司 架橋環状ピリミジノン類化合物、その製造方法、その組成物及び使用
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
JP2025527291A (ja) * 2022-08-04 2025-08-20 ４ビー テクノロジーズ （ベイジン） カンパニー リミテッド Ｌｐ－ＰＬＡ２阻害剤としてのジヒドロイミダゾピリミジノン化合物およびその使用
JP2026516205A (ja) * 2023-04-18 2026-05-20 サイニューロ セラピューティクス インコーポレイテッド Ｌｐ－ｐｌａ２阻害剤と第２の薬剤の併用治療
CN118221687B (zh) * 2023-07-17 2024-12-31 上海枢境生物科技有限公司 双环[5,6]咪唑嘧啶酮类衍生物、其制备方法和应用
WO2025217646A1 (en) * 2024-04-12 2025-10-16 Scineuro Therapeutics Inc. Method of treating neurodegenerative and ocular neovascular diseases

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AU2003250470A1 (en) * 2002-08-13 2004-02-25 Warner-Lambert Company Llc Pyrimidinone fused bicyclic metalloproteinase inhibitors
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JP2016505053A (ja) 2013-01-25 2016-02-18 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ Ｌｐ‐ＰＬＡ２の阻害剤としての二環式ピリミドン化合物
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CA2970537A1 (en) 2016-01-28
US10428078B2 (en) 2019-10-01
RU2017105353A (ru) 2018-08-22
CA2955910A1 (en) 2016-01-28
CN106536521A (zh) 2017-03-22
EP3172211B1 (en) 2019-07-03
JP2017520613A (ja) 2017-07-27
CA2955910C (en) 2022-07-12
ES2744339T3 (es) 2020-02-24
AU2015292049B2 (en) 2017-06-15
CN106536525A (zh) 2017-03-22
AR101261A1 (es) 2016-12-07
UY36224A (es) 2016-01-29
BR112016030939B1 (pt) 2023-10-24
US11999746B2 (en) 2024-06-04
ES2747636T3 (es) 2020-03-11
RU2017105476A3 (enExample) 2019-02-28
JP2017521456A (ja) 2017-08-03
JP6625603B2 (ja) 2019-12-25
CN106536521B (zh) 2018-08-03
AU2015292048A1 (en) 2016-12-15
AU2015292048B2 (en) 2017-06-29
US20200055863A1 (en) 2020-02-20
EP3172211A1 (en) 2017-05-31
EP3172208B1 (en) 2019-06-12
BR112016030939A2 (enExample) 2017-08-22
EP3172208A4 (en) 2017-12-06
US20170204109A1 (en) 2017-07-20
KR20170034889A (ko) 2017-03-29
WO2016011931A1 (en) 2016-01-28
US20240300965A1 (en) 2024-09-12
CN106536525B (zh) 2019-05-03
AU2015292049A1 (en) 2016-12-15
RU2017105476A (ru) 2018-08-28
WO2016011930A1 (en) 2016-01-28
EP3172208A1 (en) 2017-05-31
US9783546B2 (en) 2017-10-10
US10125141B2 (en) 2018-11-13
BR112016028591A2 (pt) 2017-08-22
EP3172211A4 (en) 2018-02-14
RU2690190C2 (ru) 2019-05-31
US20170204108A1 (en) 2017-07-20
JP6625604B2 (ja) 2019-12-25
US20190023715A1 (en) 2019-01-24
RU2017105353A3 (enExample) 2018-11-26
TW201617348A (zh) 2016-05-16
KR20170029516A (ko) 2017-03-15

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