KR102071278B1 - Cgrp 수용체 길항제의 제조 방법 - Google Patents

Cgrp 수용체 길항제의 제조 방법 Download PDF

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KR102071278B1
KR102071278B1 KR1020147025146A KR20147025146A KR102071278B1 KR 102071278 B1 KR102071278 B1 KR 102071278B1 KR 1020147025146 A KR1020147025146 A KR 1020147025146A KR 20147025146 A KR20147025146 A KR 20147025146A KR 102071278 B1 KR102071278 B1 KR 102071278B1
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formula
compound
alkyl
solution
methyl
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KR20140138705A (ko
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케빈 엠. 벨릭
에드워드 클이에이터
셴-춘 쿠오
피터 엠마뉴엘 말리그레스
방핑 지앙
노부요시 야수다
지앙규오 인
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머크 샤프 앤드 돔 코포레이션
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    • 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
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P11/06—Antiasthmatics
    • 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
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/06—Antimigraine agents
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/36—Opioid-abuse
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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 two hetero rings
    • C07D405/12—Heterocyclic 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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Pulmonology (AREA)
  • Psychiatry (AREA)
  • Addiction (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Immunology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Epidemiology (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Pyridine Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)
KR1020147025146A 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법 Active KR102071278B1 (ko)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261610746P 2012-03-14 2012-03-14
US61/610,746 2012-03-14
US201261644648P 2012-05-09 2012-05-09
US61/644,648 2012-05-09
PCT/US2013/030696 WO2013138418A2 (en) 2012-03-14 2013-03-13 Process for making cgrp receptor antagonists

Related Child Applications (1)

Application Number Title Priority Date Filing Date
KR1020207001976A Division KR102220242B1 (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법

Publications (2)

Publication Number Publication Date
KR20140138705A KR20140138705A (ko) 2014-12-04
KR102071278B1 true KR102071278B1 (ko) 2020-03-03

Family

ID=49161940

Family Applications (7)

Application Number Title Priority Date Filing Date
KR1020147025146A Active KR102071278B1 (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020247001330A Ceased KR20240010553A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020207001976A Active KR102220242B1 (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020217029942A Abandoned KR20210116717A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020217005005A Abandoned KR20210022150A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020227041223A Ceased KR20220164616A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020257005576A Pending KR20250028525A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법

Family Applications After (6)

Application Number Title Priority Date Filing Date
KR1020247001330A Ceased KR20240010553A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020207001976A Active KR102220242B1 (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020217029942A Abandoned KR20210116717A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020217005005A Abandoned KR20210022150A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020227041223A Ceased KR20220164616A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법
KR1020257005576A Pending KR20250028525A (ko) 2012-03-14 2013-03-13 Cgrp 수용체 길항제의 제조 방법

Country Status (10)

Country Link
EP (1) EP2825044B1 (enExample)
JP (3) JP6212534B2 (enExample)
KR (7) KR102071278B1 (enExample)
CN (1) CN104168768B (enExample)
AU (1) AU2013232196C1 (enExample)
BR (1) BR112014022542A8 (enExample)
CA (1) CA2865944C (enExample)
MX (1) MX346252B (enExample)
RU (1) RU2672056C2 (enExample)
WO (1) WO2013138418A2 (enExample)

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US9174989B2 (en) * 2012-05-09 2015-11-03 Merck Sharp & Dohme Corp. Process for making CGRP receptor antagonists
CN105037210A (zh) * 2015-05-27 2015-11-11 江苏大学 一种α，β-脱氢-α-氨基酸的合成方法
GB201707938D0 (en) 2017-05-17 2017-06-28 Univ Sheffield Compounds
JP7690493B2 (ja) * 2020-05-04 2025-06-10 大鵬薬品工業株式会社 Ｉａｐアンタゴニスト化合物及びその中間体、並びにそれを合成する方法
WO2024134683A1 (en) * 2022-12-21 2024-06-27 Msn Laboratories Private Limited, R&D Center Novel process for the preparation of intermediate compounds used in the treatment of migraine
CN119431222B (zh) * 2024-11-04 2025-10-17 杭州澳赛诺生物科技有限公司 一种不对称合成乌布吉泮手性中间体的方法
CN119350337A (zh) * 2024-12-24 2025-01-24 药康众拓(北京)医药科技有限公司 一类氘代哌啶酮酸酰胺氮杂茚满类cgrp抑制剂药物及用途
CN120398716A (zh) * 2025-04-17 2025-08-01 珠海奥博凯生物医药技术有限公司 一种基于连续流反应技术合成5-氰基-2-氟苯基化合物的方法

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WO2008073251A1 (en) 2006-12-08 2008-06-19 Merck & Co., Inc. Constrained spirocyclic compounds as cgrp receptor antagonists
WO2011005731A2 (en) 2009-07-08 2011-01-13 Merck Sharp & Dohme Corp. Process for making cgrp receptor antagonist
WO2012064911A1 (en) 2010-11-12 2012-05-18 Merck Sharp & Dohme Corp. Piperidinone carboxamide indane cgrp receptor antagonists

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WO2007133491A1 (en) * 2006-05-09 2007-11-22 Merck & Co., Inc. Substituted spirocyclic cgrp receptor antagonists
US8097750B2 (en) * 2006-12-20 2012-01-17 Brandeis University Cinchona alkaloid-catalyzed asymmetric mannich reactions
US8143266B2 (en) * 2007-04-16 2012-03-27 Merck, Sharp & Dohme Corp Aryl heterocyclic CGRP receptor antagonists
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JP5233457B2 (ja) * 2007-07-17 2013-07-10 セントラル硝子株式会社 新規な含フッ素ジカルボン酸およびそれを用いた新規な高分子化合物
KR101098335B1 (ko) * 2008-07-18 2011-12-26 성균관대학교산학협력단 신코나 기재 이작용성 유기 촉매 및 이를 이용한 메소-고리산무수물의 비대칭 고리 열림 반응을 통한 키랄성헤미에스터의 제조방법
WO2010021864A1 (en) * 2008-08-20 2010-02-25 Merck Sharp & Dohme Corp. Non-amidic linkers with branched termini as cgrp receptor antagonists
CA2771226A1 (en) * 2008-08-22 2010-02-25 James Madden New bradykinin b1 antagonists
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EP2438067B1 (de) * 2009-06-05 2015-08-26 Boehringer Ingelheim International GmbH Spirolactame als cgrp-antagonisten
WO2011014383A1 (en) * 2009-07-27 2011-02-03 Merck Sharp & Dohme Corp. Radiolabeled cgrp antagonists
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Publication number Priority date Publication date Assignee Title
WO2008073251A1 (en) 2006-12-08 2008-06-19 Merck & Co., Inc. Constrained spirocyclic compounds as cgrp receptor antagonists
WO2011005731A2 (en) 2009-07-08 2011-01-13 Merck Sharp & Dohme Corp. Process for making cgrp receptor antagonist
WO2012064911A1 (en) 2010-11-12 2012-05-18 Merck Sharp & Dohme Corp. Piperidinone carboxamide indane cgrp receptor antagonists

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EP2825044A4 (en) 2015-12-02
MX2014011000A (es) 2014-10-13
KR20140138705A (ko) 2014-12-04
KR20240010553A (ko) 2024-01-23
KR20210022150A (ko) 2021-03-02
CN104168768A (zh) 2014-11-26
WO2013138418A2 (en) 2013-09-19
WO2013138418A3 (en) 2014-05-30
CA2865944C (en) 2020-12-08
MX346252B (es) 2017-03-10
CN104168768B (zh) 2017-03-01
AU2013232196B2 (en) 2016-12-01
KR102220242B1 (ko) 2021-02-25
JP6572273B2 (ja) 2019-09-04
KR20220164616A (ko) 2022-12-13
EP2825044A2 (en) 2015-01-21
RU2014141158A (ru) 2016-05-10
AU2013232196C1 (en) 2017-03-16
JP2015516946A (ja) 2015-06-18
KR20200011559A (ko) 2020-02-03
JP6212534B2 (ja) 2017-10-11
KR20210116717A (ko) 2021-09-27
EP2825044B1 (en) 2018-08-15
CA2865944A1 (en) 2013-09-19
JP2018030858A (ja) 2018-03-01
AU2013232196A1 (en) 2014-08-21
JP6743256B2 (ja) 2020-08-19
BR112014022542A2 (enExample) 2017-06-20
RU2672056C2 (ru) 2018-11-09
JP2019206586A (ja) 2019-12-05
KR20250028525A (ko) 2025-02-28
BR112014022542A8 (pt) 2023-04-11

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