MX2017015574A - Inhibidores de tirosina quinasa de bruton. - Google Patents
Inhibidores de tirosina quinasa de bruton.Info
- Publication number
- MX2017015574A MX2017015574A MX2017015574A MX2017015574A MX2017015574A MX 2017015574 A MX2017015574 A MX 2017015574A MX 2017015574 A MX2017015574 A MX 2017015574A MX 2017015574 A MX2017015574 A MX 2017015574A MX 2017015574 A MX2017015574 A MX 2017015574A
- Authority
- MX
- Mexico
- Prior art keywords
- inhibitors
- bruton
- tyrosine kinase
- conditions
- disclosed
- Prior art date
Links
- 102000001714 Agammaglobulinaemia Tyrosine Kinase Human genes 0.000 title abstract 2
- 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 title abstract 2
- 239000003112 inhibitor Substances 0.000 title abstract 2
- 208000023275 Autoimmune disease Diseases 0.000 abstract 1
- 229940124291 BTK inhibitor Drugs 0.000 abstract 1
- 206010025323 Lymphomas Diseases 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 208000027866 inflammatory disease Diseases 0.000 abstract 1
- 230000002427 irreversible effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000002441 reversible effect Effects 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero 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
- A61K31/495—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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- 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
-
- 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
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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
-
- 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
- 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
- C07D471/08—Bridged systems
Landscapes
- 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)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562169945P | 2015-06-02 | 2015-06-02 | |
| US201562169935P | 2015-06-02 | 2015-06-02 | |
| US201562169941P | 2015-06-02 | 2015-06-02 | |
| US201562249338P | 2015-11-01 | 2015-11-01 | |
| US201562249340P | 2015-11-01 | 2015-11-01 | |
| US201562249336P | 2015-11-01 | 2015-11-01 | |
| PCT/US2016/035489 WO2016196776A2 (en) | 2015-06-02 | 2016-06-02 | Inhibitors of bruton's tyrosine kinase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2017015574A true MX2017015574A (es) | 2018-08-09 |
Family
ID=57441893
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2017015574A MX2017015574A (es) | 2015-06-02 | 2016-06-02 | Inhibidores de tirosina quinasa de bruton. |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US20180305348A1 (OSRAM) |
| EP (1) | EP3310776A4 (OSRAM) |
| JP (1) | JP2018522823A (OSRAM) |
| KR (1) | KR20180021740A (OSRAM) |
| CN (1) | CN107709315A (OSRAM) |
| AU (2) | AU2016270907B2 (OSRAM) |
| BR (1) | BR112017025986A2 (OSRAM) |
| CA (1) | CA2987054A1 (OSRAM) |
| IL (1) | IL255831A (OSRAM) |
| MA (1) | MA42623A (OSRAM) |
| MX (1) | MX2017015574A (OSRAM) |
| RU (1) | RU2017145650A (OSRAM) |
| SG (1) | SG10201911523YA (OSRAM) |
| WO (1) | WO2016196776A2 (OSRAM) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10858364B2 (en) * | 2016-12-21 | 2020-12-08 | Acerta Pharma B.V. | Imidazopyrazine inhibitors of Bruton's tyrosine kinase |
| KR101956815B1 (ko) * | 2017-02-14 | 2019-03-12 | 한국화학연구원 | 트리아졸로피리다진 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 브루톤티로신 키나제 활성 관련 질환의 예방 또는 치료용 약학적 조성물 |
| CN109384774B (zh) * | 2017-08-11 | 2023-02-17 | 中国科学院上海药物研究所 | 一类多取代的吡嗪/三嗪酰胺类化合物及其制备方法和应用 |
| CN108530450B (zh) * | 2018-05-03 | 2021-03-30 | 赖建智 | 具有egfr抑制活性的化合物、制备方法及其在疾病治疗中的应用 |
| CN112469414A (zh) | 2018-05-25 | 2021-03-09 | 昂科库博疗法有限责任公司 | 作为新型候选抗癌药物的高效力tacc3抑制剂 |
| AU2019360928B2 (en) | 2018-10-15 | 2023-11-09 | Nurix Therapeutics, Inc. | Bifunctional compounds for degrading BTK via ubiquitin proteosome pathway |
| FI3870579T3 (fi) * | 2018-10-22 | 2025-01-02 | Alumis Inc | Tyk2-inhibiittoreita ja niiden käyttöjä |
| US20220143195A1 (en) * | 2019-02-13 | 2022-05-12 | Nurix Therapeutics, Inc. | Bifunctional compounds for degrading btk via ubiquitin proteosome pathway |
| KR20210142154A (ko) | 2019-03-21 | 2021-11-24 | 옹쎄오 | 암 치료를 위한 키나제 억제제와 조합된 dbait 분자 |
| WO2020210508A1 (en) | 2019-04-09 | 2020-10-15 | Nurix Therapeutics, Inc. | 3-substituted piperidine compounds for cbl-b inhibition, and use of a cbl-b inhibitor in combination with a cancer vaccine and/or oncolytic virus |
| CN114206855B (zh) | 2019-05-17 | 2024-11-26 | 紐力克斯治疗公司 | 用于Cbl-b抑制的氰基环丁基类化合物及其用途 |
| BR112021026241A2 (pt) | 2019-06-26 | 2022-06-07 | Nurix Therapeutics Inc | Compostos de benzil-triazol substituído para inibição de cbl-b e outros usos dos mesmos |
| AU2020353015A1 (en) | 2019-09-24 | 2022-03-31 | Nurix Therapeutics, Inc. | CBL inhibitors and compositions for use in adoptive cell therapy |
| JP2023500906A (ja) | 2019-11-08 | 2023-01-11 | インサーム（インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル） | キナーゼ阻害剤に対する獲得抵抗性を有するがんの処置方法 |
| JP2023504147A (ja) | 2019-12-04 | 2023-02-01 | ニューリックス セラピューティクス，インコーポレイテッド | ユビキチンプロテオソーム経路を介したｂｔｋの分解のための二官能性化合物 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| KR20230019444A (ko) * | 2020-06-01 | 2023-02-08 | 위겐 바이오메더슨 테크널러지 (상하이) 컴퍼니 리미티드 | 신규한 피라진 화합물 |
| WO2022071772A1 (ko) * | 2020-09-29 | 2022-04-07 | (주)메디톡스 | 단백질 키나제 저해제 및 그의 용도 |
| JP2024514836A (ja) | 2021-04-08 | 2024-04-03 | ニューリックス セラピューティクス，インコーポレイテッド | Ｃｂｌ－ｂ阻害化合物との組み合わせ療法 |
| KR20240005751A (ko) * | 2021-04-12 | 2024-01-12 | 에이2에이 파마수티칼스, 잉크. | 암 치료를 위한 조성물 및 방법 |
| KR20240029070A (ko) * | 2021-07-01 | 2024-03-05 | 항저우 힐젠 테라퓨틱스 컴퍼니 리미티드 | 브루톤 티로신 키나아제, 이의 돌연변이체 분해제, 조성물 및 응용 |
| JP2024542984A (ja) | 2021-10-26 | 2024-11-19 | ニューリックス セラピューティクス，インコーポレイテッド | がんを治療および予防するためのピペリジニルピラジン－カルボキサミド化合物、およびｂｔｋを分解するためのピペリジニルピラジン－カルボキサミド化合物 |
| CN118598858A (zh) * | 2021-11-22 | 2024-09-06 | 杭州和正医药有限公司 | 一种可降解btk激酶的多功能化合物、组合物及应用 |
| JP2025509965A (ja) | 2022-03-24 | 2025-04-11 | エーツーエー ファーマシューティカルズ インコーポレーテッド | がんを治療するための組成物及び方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4622047B2 (ja) * | 1999-06-09 | 2011-02-02 | アステラス製薬株式会社 | 新規なヘテロ環カルボキサミド誘導体 |
| DE60017898T2 (de) * | 1999-06-09 | 2006-01-12 | Yamanouchi Pharmaceutical Co., Ltd. | Neuartige heterocyclische carboxamidderivate |
| JP2014005206A (ja) * | 2010-10-22 | 2014-01-16 | Astellas Pharma Inc | アリールアミノヘテロ環カルボキサミド化合物 |
| JP5878178B2 (ja) * | 2011-09-30 | 2016-03-08 | 大鵬薬品工業株式会社 | １，２，４−トリアジン−６−カルボキサミド誘導体 |
| EP2763976B1 (en) * | 2011-10-05 | 2016-05-18 | Merck Sharp & Dohme Corp. | 2-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors |
| CA2856301C (en) * | 2011-11-23 | 2020-10-06 | Portola Pharmaceuticals, Inc. | Pyrazine kinase inhibitors |
| CN104159891B (zh) * | 2012-01-10 | 2016-09-07 | 霍夫曼-拉罗奇有限公司 | 哒嗪酰胺化合物和它们作为syk 抑制剂的用途 |
| US9085540B2 (en) * | 2012-01-17 | 2015-07-21 | Astellas Pharma Inc. | Pyrazinecarboxamide compound |
| US20140113931A1 (en) * | 2012-06-22 | 2014-04-24 | Portola Pharmaceuticals, Inc. | Substituted picolinamide kinase inhibitors |
| US9040530B2 (en) * | 2012-06-22 | 2015-05-26 | Portola Pharmaceuticals, Inc. | 1,2,4-triazine-6-carboxamide kinase inhibitors |
| WO2014135473A1 (en) * | 2013-03-05 | 2014-09-12 | F. Hoffmann-La Roche Ag | Inhibitors of bruton's tyrosine kinase |
| WO2014153280A1 (en) * | 2013-03-22 | 2014-09-25 | Merck Sharp & Dohme Corp. | 2-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors |
| WO2015039613A1 (zh) * | 2013-09-18 | 2015-03-26 | 北京韩美药品有限公司 | 抑制btk和/或jak3激酶活性的化合物 |
| JP6345786B2 (ja) * | 2013-12-05 | 2018-06-20 | ファーマサイクリックス エルエルシー | ブルトン型チロシンキナーゼの阻害剤 |
-
2016
- 2016-06-02 JP JP2017560655A patent/JP2018522823A/ja active Pending
- 2016-06-02 MA MA042623A patent/MA42623A/fr unknown
- 2016-06-02 EP EP16804424.6A patent/EP3310776A4/en not_active Withdrawn
- 2016-06-02 US US15/579,142 patent/US20180305348A1/en not_active Abandoned
- 2016-06-02 BR BR112017025986A patent/BR112017025986A2/pt not_active IP Right Cessation
- 2016-06-02 RU RU2017145650A patent/RU2017145650A/ru not_active Application Discontinuation
- 2016-06-02 CA CA2987054A patent/CA2987054A1/en not_active Abandoned
- 2016-06-02 AU AU2016270907A patent/AU2016270907B2/en not_active Ceased
- 2016-06-02 KR KR1020177037849A patent/KR20180021740A/ko not_active Withdrawn
- 2016-06-02 WO PCT/US2016/035489 patent/WO2016196776A2/en not_active Ceased
- 2016-06-02 SG SG10201911523YA patent/SG10201911523YA/en unknown
- 2016-06-02 MX MX2017015574A patent/MX2017015574A/es unknown
- 2016-06-02 CN CN201680035113.2A patent/CN107709315A/zh active Pending
-
2017
- 2017-11-21 IL IL255831A patent/IL255831A/en unknown
-
2019
- 2019-07-17 US US16/514,544 patent/US20210070748A1/en not_active Abandoned
-
2020
- 2020-12-11 AU AU2020286332A patent/AU2020286332A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016196776A3 (en) | 2017-01-05 |
| SG10201911523YA (en) | 2020-02-27 |
| AU2020286332A1 (en) | 2021-01-21 |
| RU2017145650A3 (OSRAM) | 2019-11-22 |
| KR20180021740A (ko) | 2018-03-05 |
| MA42623A (fr) | 2018-06-20 |
| BR112017025986A2 (pt) | 2018-08-14 |
| EP3310776A2 (en) | 2018-04-25 |
| AU2016270907B2 (en) | 2020-09-17 |
| EP3310776A4 (en) | 2019-01-16 |
| RU2017145650A (ru) | 2019-07-15 |
| IL255831A (en) | 2018-01-31 |
| WO2016196776A2 (en) | 2016-12-08 |
| CN107709315A (zh) | 2018-02-16 |
| CA2987054A1 (en) | 2016-12-08 |
| JP2018522823A (ja) | 2018-08-16 |
| AU2016270907A1 (en) | 2017-12-07 |
| US20210070748A1 (en) | 2021-03-11 |
| US20180305348A1 (en) | 2018-10-25 |
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