CL2016000400A1 - Moduladores del receptor p2x3 y p2x2/3 de diaminopiridina para el tratamiento de la tos aguda, sub-aguda o crónica. - Google Patents
Moduladores del receptor p2x3 y p2x2/3 de diaminopiridina para el tratamiento de la tos aguda, sub-aguda o crónica.Info
- Publication number
- CL2016000400A1 CL2016000400A1 CL2016000400A CL2016000400A CL2016000400A1 CL 2016000400 A1 CL2016000400 A1 CL 2016000400A1 CL 2016000400 A CL2016000400 A CL 2016000400A CL 2016000400 A CL2016000400 A CL 2016000400A CL 2016000400 A1 CL2016000400 A1 CL 2016000400A1
- Authority
- CL
- Chile
- Prior art keywords
- acute
- diaminopyridine
- modulators
- receptor
- sub
- Prior art date
Links
- 230000001154 acute effect Effects 0.000 title abstract 2
- 206010011224 Cough Diseases 0.000 title 1
- 208000013116 chronic cough Diseases 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 2
- 206010020751 Hypersensitivity Diseases 0.000 abstract 1
- 208000026935 allergic disease Diseases 0.000 abstract 1
- 230000001684 chronic effect Effects 0.000 abstract 1
- 230000009610 hypersensitivity Effects 0.000 abstract 1
- 230000001537 neural effect Effects 0.000 abstract 1
Classifications
-
- 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
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- 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
-
- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/48—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive 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
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Otolaryngology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pulmonology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361869174P | 2013-08-23 | 2013-08-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CL2016000400A1 true CL2016000400A1 (es) | 2017-01-20 |
Family
ID=52480919
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CL2016000400A CL2016000400A1 (es) | 2013-08-23 | 2016-02-22 | Moduladores del receptor p2x3 y p2x2/3 de diaminopiridina para el tratamiento de la tos aguda, sub-aguda o crónica. |
| CL2018002138A CL2018002138A1 (es) | 2013-08-23 | 2018-08-08 | Moduladores del receptor p2x3 y p2x2/3 de diaminopiridina para el tratamiento de la tos aguda, subaguda o crónica.(divisional solicitud 201600400) |
| CL2018002137A CL2018002137A1 (es) | 2013-08-23 | 2018-08-08 | Moduladores del receptor p2x3 y p2x2/3 de diaminopiridina para el tratamiento de la tos aguda, subaguda o crónica.(divisional solicitud 201600400) |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CL2018002138A CL2018002138A1 (es) | 2013-08-23 | 2018-08-08 | Moduladores del receptor p2x3 y p2x2/3 de diaminopiridina para el tratamiento de la tos aguda, subaguda o crónica.(divisional solicitud 201600400) |
| CL2018002137A CL2018002137A1 (es) | 2013-08-23 | 2018-08-08 | Moduladores del receptor p2x3 y p2x2/3 de diaminopiridina para el tratamiento de la tos aguda, subaguda o crónica.(divisional solicitud 201600400) |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US9284279B2 (https=) |
| EP (2) | EP3035932A4 (https=) |
| JP (3) | JP6546592B2 (https=) |
| KR (1) | KR102196885B1 (https=) |
| CN (1) | CN105682659B (https=) |
| AU (1) | AU2014308606B2 (https=) |
| CA (1) | CA2921395C (https=) |
| CL (3) | CL2016000400A1 (https=) |
| CR (1) | CR20160093A (https=) |
| IL (1) | IL244131B (https=) |
| MX (1) | MX367657B (https=) |
| MY (1) | MY195728A (https=) |
| NI (1) | NI201600029A (https=) |
| NZ (1) | NZ716977A (https=) |
| PE (1) | PE20160431A1 (https=) |
| PH (1) | PH12016500357A1 (https=) |
| RU (1) | RU2650118C2 (https=) |
| SG (1) | SG11201601145RA (https=) |
| UA (1) | UA118851C2 (https=) |
| WO (1) | WO2015027212A1 (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2014308606B2 (en) * | 2013-08-23 | 2017-08-03 | Afferent Pharmaceuticals Inc. | Diaminopyrimidine P2X3 and P2X 2/3 receptor modulators for treatment of acute, sub-acute or chronic cough |
| ES2792682T3 (es) | 2014-02-10 | 2020-11-11 | Respivant Sciences Gmbh | Métodos para el tratamiento de enfermedades pulmonares con estabilizadores de mastocitos |
| PL3104853T3 (pl) | 2014-02-10 | 2020-05-18 | Respivant Sciences Gmbh | Leczenie stabilizatorami komórek tucznych zaburzeń ogólnoustrojowych |
| WO2017011729A1 (en) | 2015-07-16 | 2017-01-19 | Patara Pharma, LLC | Combination therapies for the treatment of lung diseases |
| WO2017027402A1 (en) | 2015-08-07 | 2017-02-16 | Patara Pharma, LLC | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
| US10238625B2 (en) | 2015-08-07 | 2019-03-26 | Respivant Sciences Gmbh | Methods for the treatment of mast cell related disorders with mast cell stabilizers |
| DK3355889T3 (da) * | 2015-09-29 | 2023-05-15 | Afferent Pharmaceuticals Inc | Diaminopyrimidin-p2x3- og p2x2/3-receptormodulatorer til anvendelse i behandling af hoste |
| US9907795B2 (en) * | 2016-01-08 | 2018-03-06 | Nerre Therapeutics Limited | Method of treatment of chronic cough administering orvepitant in combination with other therapeutic agents |
| AU2017237929B2 (en) | 2016-03-25 | 2021-04-15 | Afferent Pharmaceuticals Inc. | Pyrimidines and variants thereof, and uses therefor |
| WO2018044942A1 (en) | 2016-08-31 | 2018-03-08 | Patara Pharma, LLC | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
| EP3522983A4 (en) | 2016-10-07 | 2020-06-03 | Respivant Sciences GmbH | CROMOLYN COMPOSITION FOR TREATING LUNG FIBROSIS |
| WO2018111738A1 (en) * | 2016-12-15 | 2018-06-21 | Afferent Pharmaceuticals, Inc. | Substituted pyrazole-pyrimidines, variants thereof, and uses therefore |
| CN110087654A (zh) * | 2016-12-20 | 2019-08-02 | 传入制药公司 | P2x3拮抗剂的结晶盐和多晶型物 |
| US10111883B1 (en) * | 2017-09-18 | 2018-10-30 | Bellus Health Cough Inc. | Selective P2X3 modulators |
| CN108904507A (zh) * | 2018-02-11 | 2018-11-30 | 赖英杰 | P2x3受体调节剂苯并咪唑化合物在制备抗呼吸疾病药物中的应用 |
| EP3765072B1 (en) | 2018-03-15 | 2024-07-31 | Danmir Therapeutics, LLC | 3",5"-dialkoxybenzoyl-3'-amino-3'-deoxyadenosine-5'-triphosphates and pharmaceutical uses thereof |
| EP3784242A4 (en) * | 2018-04-23 | 2021-12-22 | Merck Sharp & Dohme Corp. | NEW PROCESS FOR PREPARING A PHENOXYDIAMINOPYRIMIDINE COMPOUND |
| EP3793553A1 (en) | 2018-05-15 | 2021-03-24 | Bayer Aktiengesellschaft | 1,3-thiazol-2-yl substituted benzamides for the treatment of diseases associated with nerve fiber sensitization |
| EA202092678A1 (ru) | 2018-05-15 | 2021-04-12 | Байер Акциенгезельшафт | 1,3-тиазол-2-ил-замещенные бензамиды для лечения заболеваний, ассоциированных с сенситизацией нервных волокон |
| IL318587A (en) * | 2018-07-23 | 2025-03-01 | Trevi Therapeutics Inc | Treatment of chronic cough, shortness of breath and wheezing |
| ES2963702T3 (es) | 2018-10-05 | 2024-04-01 | Shionogi & Co | Medicina para tratar la tos crónica |
| JP7578602B2 (ja) | 2019-02-25 | 2024-11-06 | 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、（ナンバー３）、リミテッド | Ｐ２ｘ３修飾薬での治療 |
| ES3056709T3 (en) * | 2019-04-30 | 2026-02-24 | Beijing Tide Pharmaceutical Co Ltd | Salt of diaminopyrimidine compounds, and solid form thereof, preparation method therefor and use thereof |
| BR112021021600A2 (pt) * | 2019-04-30 | 2022-01-04 | Beijing Tide Pharmaceutical Co Ltd | Método para tratamento de tosse usando composto de diaminopirimidina |
| TWI889708B (zh) | 2019-09-19 | 2025-07-11 | 日商塩野義製藥股份有限公司 | 1，3，5-三衍生物或其溶劑合物之結晶及其製造方法 |
| IL294601A (en) | 2020-01-10 | 2022-09-01 | Trevi Therapeutics Inc | Methods of administration of nalbuphine |
| CN111635368B (zh) * | 2020-06-12 | 2021-06-29 | 东莞市东阳光仿制药研发有限公司 | 一种胺化合物的制备方法 |
| WO2024080126A1 (ja) | 2022-10-12 | 2024-04-18 | ソフトバンクグループ株式会社 | 情報処理システム、情報処理装置、制御装置及びプログラム |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2557372C (en) | 2004-03-05 | 2013-01-08 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 antagonists |
| JP2008507368A (ja) * | 2004-07-22 | 2008-03-13 | デュスカ サイエンティフィック カンパニー | 肺疾患を診断、モニタリングおよび治療するための方法 |
| CN101300012B (zh) * | 2005-09-01 | 2011-09-14 | 弗·哈夫曼-拉罗切有限公司 | 作为p2x3和p2x2/3调节剂的二氨基嘧啶类化合物在制备治疗呼吸系统疾病的药物中的应用 |
| WO2007025898A1 (en) | 2005-09-01 | 2007-03-08 | F. Hoffmann-La Roche Ag | Process for synthesis of aryloxy diaminopyrimidines |
| ES2562056T3 (es) | 2005-09-01 | 2016-03-02 | F. Hoffmann-La Roche Ag | Diaminopirimidinas como moduladores P2X3 y P2X2/3 |
| EP1924564B1 (en) * | 2005-09-01 | 2016-11-09 | F.Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 modulators |
| AU2007304280B2 (en) * | 2006-10-04 | 2013-01-31 | F. Hoffmann-La Roche Ag | Process for synthesis of phenoxy diaminopyrimidine derivatives |
| WO2008104474A1 (en) * | 2007-02-28 | 2008-09-04 | F. Hoffmann-La Roche Ag | Diaminopyrimidines |
| WO2013118855A1 (ja) * | 2012-02-09 | 2013-08-15 | 塩野義製薬株式会社 | 複素環および炭素環誘導体 |
| AU2014308606B2 (en) | 2013-08-23 | 2017-08-03 | Afferent Pharmaceuticals Inc. | Diaminopyrimidine P2X3 and P2X 2/3 receptor modulators for treatment of acute, sub-acute or chronic cough |
| US9133647B2 (en) * | 2013-10-11 | 2015-09-15 | Nexkey, Inc. | NFC or BLE based contactless lock with charge monitoring of its energy storage |
-
2014
- 2014-08-22 AU AU2014308606A patent/AU2014308606B2/en active Active
- 2014-08-22 WO PCT/US2014/052389 patent/WO2015027212A1/en not_active Ceased
- 2014-08-22 CA CA2921395A patent/CA2921395C/en active Active
- 2014-08-22 CR CR20160093A patent/CR20160093A/es unknown
- 2014-08-22 MX MX2016002289A patent/MX367657B/es active IP Right Grant
- 2014-08-22 US US14/466,713 patent/US9284279B2/en active Active
- 2014-08-22 PE PE2016000285A patent/PE20160431A1/es unknown
- 2014-08-22 JP JP2016536497A patent/JP6546592B2/ja active Active
- 2014-08-22 EP EP14838254.2A patent/EP3035932A4/en not_active Withdrawn
- 2014-08-22 CN CN201480058491.3A patent/CN105682659B/zh active Active
- 2014-08-22 KR KR1020167007167A patent/KR102196885B1/ko active Active
- 2014-08-22 EP EP21159088.0A patent/EP3865134A1/en active Pending
- 2014-08-22 RU RU2016105581A patent/RU2650118C2/ru active
- 2014-08-22 SG SG11201601145RA patent/SG11201601145RA/en unknown
- 2014-08-22 MY MYPI2016000327A patent/MY195728A/en unknown
- 2014-08-22 NZ NZ716977A patent/NZ716977A/en unknown
- 2014-08-22 UA UAA201601740A patent/UA118851C2/uk unknown
-
2016
- 2016-02-02 US US15/013,798 patent/US9724346B2/en active Active
- 2016-02-15 IL IL244131A patent/IL244131B/en active IP Right Grant
- 2016-02-22 CL CL2016000400A patent/CL2016000400A1/es unknown
- 2016-02-22 NI NI201600029A patent/NI201600029A/es unknown
- 2016-02-23 PH PH12016500357A patent/PH12016500357A1/en unknown
-
2017
- 2017-08-01 US US15/665,595 patent/US10206922B2/en active Active
-
2018
- 2018-08-08 CL CL2018002138A patent/CL2018002138A1/es unknown
- 2018-08-08 CL CL2018002137A patent/CL2018002137A1/es unknown
-
2019
- 2019-03-25 JP JP2019055849A patent/JP7210348B2/ja active Active
-
2022
- 2022-10-18 JP JP2022166618A patent/JP7423725B2/ja active Active
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