MX2020007318A - Compuesto heterociclico. - Google Patents
Compuesto heterociclico.Info
- Publication number
- MX2020007318A MX2020007318A MX2020007318A MX2020007318A MX2020007318A MX 2020007318 A MX2020007318 A MX 2020007318A MX 2020007318 A MX2020007318 A MX 2020007318A MX 2020007318 A MX2020007318 A MX 2020007318A MX 2020007318 A MX2020007318 A MX 2020007318A
- Authority
- MX
- Mexico
- Prior art keywords
- disease
- pain
- heterocyclic compound
- compound
- hutchinson
- Prior art date
Links
Classifications
-
- 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
- C07D487/10—Spiro-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
- A61K31/40—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
- A61K31/407—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 other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
-
- 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
- A61P25/14—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
- A61P25/22—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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D498/02—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 two hetero rings
- C07D498/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/99—Enzyme inactivation by chemical treatment
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (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
La presente invención se refiere a un compuesto que tiene una acción inhibidora de MAGL y que se espera sea útil como un agente para la profilaxis o tratamiento de enfermedades neurodegenerativas (por ejemplo, enfermedad de Alzheimer, enfermedad de Parkinson, enfermedad de Huntington, esclerosis lateral amiotrófica, lesión cerebral traumática, glaucoma, esclerosis múltiple, etc.), trastorno de ansiedad, dolores (por ejemplo, dolor inflamatorio, dolor canceroso, dolor neurogénico, etc.), epilepsia, depresión y similares. La presente invención se refiere a un compuesto representado por la Fórmula (I): (ver Fórmula) donde cada símbolo es como se define en la descripción, o una sal del mismo.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2017190838 | 2017-09-29 | ||
PCT/JP2018/035827 WO2019065791A1 (ja) | 2017-09-29 | 2018-09-27 | 複素環化合物 |
Publications (1)
Publication Number | Publication Date |
---|---|
MX2020007318A true MX2020007318A (es) | 2020-08-24 |
Family
ID=65901896
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
MX2020007318A MX2020007318A (es) | 2017-09-29 | 2018-09-27 | Compuesto heterociclico. |
Country Status (11)
Country | Link |
---|---|
US (1) | US11274101B2 (es) |
EP (1) | EP3689879A4 (es) |
JP (1) | JP7189143B2 (es) |
KR (1) | KR102668900B1 (es) |
CN (1) | CN111148746B (es) |
AU (1) | AU2018338855B2 (es) |
BR (1) | BR112020005720A2 (es) |
CA (1) | CA3076477A1 (es) |
CO (1) | CO2020003932A2 (es) |
MX (1) | MX2020007318A (es) |
WO (1) | WO2019065791A1 (es) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR114136A1 (es) | 2017-10-10 | 2020-07-29 | Hoffmann La Roche | Compuestos heterocíclicos |
TW201936602A (zh) | 2017-11-28 | 2019-09-16 | 瑞士商赫孚孟拉羅股份公司 | 新雜環化合物 |
EP3737680A1 (en) | 2018-01-08 | 2020-11-18 | F. Hoffmann-La Roche AG | Octahydropyrido[1,2-alpha]pyrazines as magl inhibitors |
CN112867720A (zh) | 2018-08-13 | 2021-05-28 | 豪夫迈·罗氏有限公司 | 作为单酰基甘油脂肪酶抑制剂的新型杂环化合物 |
US11814375B2 (en) | 2019-09-12 | 2023-11-14 | Hoffmann-La Roche Inc. | Heterocyclic compounds |
JP2023512729A (ja) | 2020-02-10 | 2023-03-28 | ヤンセン ファーマシューティカ エヌ.ベー. | モノアシルグリセロールリパーゼ調節因子 |
MX2022011901A (es) | 2020-03-26 | 2023-01-04 | Janssen Pharmaceutica Nv | Arilo piperidinas como moduladores de monoacilglicerol lipasa. |
EP4126825A1 (en) | 2020-03-26 | 2023-02-08 | Janssen Pharmaceutica NV | Aminocyclobutanes as monoacylglycerol lipase modulators |
CN115362153A (zh) | 2020-03-26 | 2022-11-18 | 詹森药业有限公司 | 作为单酰基甘油脂肪酶调节剂的氮杂螺环 |
CN111574537B (zh) * | 2020-05-20 | 2022-11-15 | 成都药明康德新药开发有限公司 | 叔丁基-8-氧杂-3,11-二氮杂螺[5.6]十二烷-3-甲酸基酯的合成方法 |
CR20230115A (es) | 2020-09-03 | 2023-04-11 | Hoffmann La Roche | Compuestos heterocíclicos |
TW202328148A (zh) * | 2021-09-22 | 2023-07-16 | 日商塩野義製藥股份有限公司 | 具有血清素受體結合活性之螺雜環衍生物 |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2355690C2 (ru) | 2004-01-08 | 2009-05-20 | Ф.Хоффманн-Ля Рош Аг | Производные диазаспиропиперидина |
WO2010124112A1 (en) | 2009-04-22 | 2010-10-28 | Janssen Pharmaceutica Nv | Azetidinyl diamides as monoacylglycerol lipase inhibitors |
ES2486674T3 (es) | 2009-04-22 | 2014-08-19 | Janssen Pharmaceutica N.V. | Piperazinilazetidinilamidas heteroaromáticas y aromáticas como inhibidores de la monoacilglicerol lipasa |
WO2010124122A1 (en) | 2009-04-22 | 2010-10-28 | Janssen Pharmaceutica Nv | Heteroaromatic and aromatic piperazinyl azetidinyl amides as monoacylglycerol lipase inhibitors |
US8435977B2 (en) | 2009-04-22 | 2013-05-07 | Janssen Pharmaceutica, Nv | Heteroaromatic and aromatic piperazinyl azetidinyl amides as monoacylglycerol lipase inhibitors |
RU2013114771A (ru) | 2010-09-03 | 2014-10-10 | Янссен Фармацевтика Нв | Диамиды азетидинила как ингибиторы моноацилглицерол липазы |
CN103080103A (zh) | 2010-09-27 | 2013-05-01 | 詹森药业有限公司 | 作为单酰甘油脂肪酶抑制剂的氧代哌嗪-氮杂环丁烷酰胺和氧代二氮杂*-氮杂环丁烷酰胺 |
KR20130142137A (ko) | 2010-10-22 | 2013-12-27 | 얀센 파마슈티카 엔.브이. | 모노아실글리세롤 리파아제 억제제로서의 피페리딘-4-일-아제티딘 다이아미드 |
US8513423B2 (en) | 2010-10-22 | 2013-08-20 | Janssen Pharmaceutica, Nv | Piperidin-4-yl-azetidine diamides as monoacylglycerol lipase inhibitors |
MX2014003883A (es) | 2011-09-30 | 2014-08-27 | Janssen Pharmaceutica Nv | Inhibidores de monoacilglicerol lipasa para el tratamiento de enfermedades metabolicas y transtornos relacionados. |
KR20140068243A (ko) | 2011-09-30 | 2014-06-05 | 얀센 파마슈티카 엔.브이. | 대사 질환 및 관련 장애의 치료를 위한 모노아실글리세롤 리파제 억제제 |
CA2866302A1 (en) * | 2012-03-19 | 2013-09-26 | Abide Therapeutics, Inc. | Carbamate compounds and of making and using same |
US9127024B2 (en) | 2013-03-15 | 2015-09-08 | Intrexon Corporation | Boron-containing diacylhydrazines |
WO2015003002A1 (en) * | 2013-07-03 | 2015-01-08 | Abide Therapeutics, Inc. | Pyrrolo-pyrrole carbamate and related organic compounds, pharmaceutical compositions, and medical uses thereof |
EP3087067B1 (en) | 2013-12-26 | 2018-10-24 | Takeda Pharmaceutical Company Limited | 4-(piperrazin-1-yl)-pyrrolidin-2-one compounds as monoacylglycerol lipase (magl) inhibitors |
CN107106559A (zh) | 2014-04-04 | 2017-08-29 | X-Rx股份有限公司 | 自分泌运动因子的取代的螺环抑制剂 |
EP3279191B1 (en) | 2015-03-30 | 2020-09-02 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
ES2823049T3 (es) | 2015-07-31 | 2021-05-05 | Pfizer | Derivados de carbamato de 1,1,1-trifluoro-3-hidroxipropan-2-ilo y derivados de carbamato de 1,1,1-trifluoro-4-hidroxibutan-2-ilo como inhibidores de MAGL |
WO2017087863A1 (en) * | 2015-11-20 | 2017-05-26 | Abide Therapeutics, Inc. | Pyrazole compounds and methods of making and using same |
ES2822979T3 (es) | 2015-11-20 | 2021-05-05 | Lundbeck La Jolla Research Center Inc | Derivados de pirazol, procesos para su preparación, y sus usos |
US10610520B2 (en) * | 2016-03-31 | 2020-04-07 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
ES2804580T3 (es) | 2016-03-31 | 2021-02-08 | Takeda Pharmaceuticals Co | Compuesto heterocíclico |
JP2017190838A (ja) | 2016-04-14 | 2017-10-19 | ナブテスコ株式会社 | 風車駆動装置及び減速機 |
RU2726631C1 (ru) * | 2017-01-23 | 2020-07-15 | Пфайзер Инк. | Гетероциклические спиросоединения в качестве ингибиторов magl |
-
2018
- 2018-09-27 MX MX2020007318A patent/MX2020007318A/es unknown
- 2018-09-27 US US16/651,840 patent/US11274101B2/en active Active
- 2018-09-27 CN CN201880062466.0A patent/CN111148746B/zh active Active
- 2018-09-27 CA CA3076477A patent/CA3076477A1/en active Pending
- 2018-09-27 BR BR112020005720-7A patent/BR112020005720A2/pt unknown
- 2018-09-27 JP JP2019545593A patent/JP7189143B2/ja active Active
- 2018-09-27 WO PCT/JP2018/035827 patent/WO2019065791A1/ja active Application Filing
- 2018-09-27 KR KR1020207011080A patent/KR102668900B1/ko active IP Right Grant
- 2018-09-27 EP EP18860497.9A patent/EP3689879A4/en active Pending
- 2018-09-27 AU AU2018338855A patent/AU2018338855B2/en active Active
-
2020
- 2020-03-30 CO CONC2020/0003932A patent/CO2020003932A2/es unknown
Also Published As
Publication number | Publication date |
---|---|
CN111148746B (zh) | 2022-08-05 |
RU2020114455A (ru) | 2021-10-29 |
US20200255439A1 (en) | 2020-08-13 |
CO2020003932A2 (es) | 2020-06-19 |
EP3689879A1 (en) | 2020-08-05 |
KR20200061365A (ko) | 2020-06-02 |
US11274101B2 (en) | 2022-03-15 |
AU2018338855A1 (en) | 2020-05-07 |
WO2019065791A1 (ja) | 2019-04-04 |
EP3689879A4 (en) | 2021-07-14 |
JPWO2019065791A1 (ja) | 2020-11-05 |
RU2020114455A3 (es) | 2021-12-01 |
BR112020005720A2 (pt) | 2020-10-20 |
JP7189143B2 (ja) | 2022-12-13 |
KR102668900B1 (ko) | 2024-05-24 |
CN111148746A (zh) | 2020-05-12 |
AU2018338855B2 (en) | 2022-04-28 |
CA3076477A1 (en) | 2019-04-04 |
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