ES2234929T3 - Derivados de morfolina como antagonistas de los receptores de orexina. - Google Patents
Derivados de morfolina como antagonistas de los receptores de orexina.Info
- Publication number
- ES2234929T3 ES2234929T3 ES01994716T ES01994716T ES2234929T3 ES 2234929 T3 ES2234929 T3 ES 2234929T3 ES 01994716 T ES01994716 T ES 01994716T ES 01994716 T ES01994716 T ES 01994716T ES 2234929 T3 ES2234929 T3 ES 2234929T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- optionally substituted
- compound
- formula
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- 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
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- 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
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- 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
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- 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
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- 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
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- Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
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- Anesthesiology (AREA)
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- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
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| GB0028955 | 2000-11-28 | ||
| GB0028955A GB0028955D0 (en) | 2000-11-28 | 2000-11-28 | Compounds |
| GB0114291A GB0114291D0 (en) | 2001-06-12 | 2001-06-12 | Compounds |
| GB0114291 | 2001-06-12 |
Publications (1)
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| ES2234929T3 true ES2234929T3 (es) | 2005-07-01 |
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| ES01994716T Expired - Lifetime ES2234929T3 (es) | 2000-11-28 | 2001-11-22 | Derivados de morfolina como antagonistas de los receptores de orexina. |
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| Country | Link |
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| US (1) | US6943160B2 (enExample) |
| EP (1) | EP1353918B1 (enExample) |
| JP (1) | JP4246490B2 (enExample) |
| AT (1) | ATE286897T1 (enExample) |
| AU (1) | AU2002224885A1 (enExample) |
| DE (1) | DE60108420T2 (enExample) |
| ES (1) | ES2234929T3 (enExample) |
| WO (1) | WO2002044172A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| MXPA03010129A (es) * | 2001-05-05 | 2004-03-10 | Smithkline Beecham Plc | N-aroilaminas-ciclicas. |
| GB0115862D0 (en) * | 2001-06-28 | 2001-08-22 | Smithkline Beecham Plc | Compounds |
| GB0124463D0 (en) * | 2001-10-11 | 2001-12-05 | Smithkline Beecham Plc | Compounds |
| GB0127145D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Compounds |
| GB0130335D0 (en) * | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| CN1556705B (zh) | 2002-07-09 | 2010-04-28 | 埃科特莱茵药品有限公司 | 7,8,9,10-四氢-6H-氮杂卓并、6,7,8,9-四氢-吡啶并和2,3-二氢-2H-吡咯并[2,1-b]-喹唑啉酮衍生物 |
| WO2004026866A1 (en) * | 2002-09-18 | 2004-04-01 | Glaxo Group Limited | N-aroyl cyclic amines as orexin receptor antagonists |
| RU2334735C2 (ru) | 2002-10-11 | 2008-09-27 | Актелион Фармасьютиклз Лтд. | Производные сульфониламиноуксусной кислоты и их применение в качестве антагонистов рецепторов орексина |
| GB0225944D0 (en) * | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| GB0225938D0 (en) * | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| JP2007523846A (ja) | 2003-04-28 | 2007-08-23 | アクテリオン ファマシューティカルズ リミテッド | キノキサリノン誘導体 |
| PT1751111E (pt) | 2004-03-01 | 2015-04-01 | Actelion Pharmaceuticals Ltd | Derivados de 1,2,3,4-tetrahidroisoquinolina substituída |
| US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
| US20060178307A1 (en) * | 2005-01-26 | 2006-08-10 | The Regents Of The University Of California | Modulation of NMDA receptor currents via orexin receptor and/or CRF receptor |
| US7501395B2 (en) | 2005-04-25 | 2009-03-10 | Eisai R & D Management Co., Ltd. | Method of screening for antianxiety drugs |
| WO2006126074A2 (en) * | 2005-05-26 | 2006-11-30 | Orchid Research Laboratories Limited | Heterocyclic derivatives |
| WO2007136790A2 (en) * | 2006-05-18 | 2007-11-29 | Mannkind Corporation | Intracellular kinase inhibitors |
| JP2009543785A (ja) | 2006-07-14 | 2009-12-10 | メルク エンド カムパニー インコーポレーテッド | 架橋ジアゼパンオレキシン受容体アンタゴニスト |
| US20100016401A1 (en) * | 2006-09-29 | 2010-01-21 | Actelion Phamaceuticals Ltd. | 3-aza-bicyclo[3.1.0]hexane derivatives |
| ES2357992T3 (es) | 2006-12-01 | 2011-05-04 | Actelion Pharmaceuticals Ltd. | Derivados de 3-heteroaril(amino o amido)-1-(bifenil o feniltiazolil)carbonilpiperidina como inhibidores del receptor de orexina. |
| PE20081229A1 (es) | 2006-12-01 | 2008-08-28 | Merck & Co Inc | Antagonistas de receptor de orexina de diazepam sustituido |
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| CN101730696B (zh) * | 2007-07-03 | 2013-01-09 | 埃科特莱茵药品有限公司 | 3-氮杂-二环[3.3.0]辛烷化合物 |
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| EP2207778A2 (en) * | 2007-09-24 | 2010-07-21 | Actelion Pharmaceuticals Ltd. | Pyrrolidines and piperidines as orexin receptor antagonists |
| AU2009215243A1 (en) | 2008-02-21 | 2009-08-27 | Actelion Pharmaceuticals Ltd. | 2-aza-bicyclo[2.2.1]heptane derivatives |
| CN102015645B (zh) * | 2008-04-30 | 2012-11-14 | 埃科特莱茵药品有限公司 | 哌啶和吡咯烷化合物 |
| ES2522968T3 (es) | 2008-06-04 | 2014-11-19 | Synergy Pharmaceuticals Inc. | Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| CN102083827A (zh) * | 2008-07-07 | 2011-06-01 | 埃科特莱茵药品有限公司 | 作为食欲素受体拮抗剂的噻唑烷化合物 |
| CA2730603C (en) | 2008-07-16 | 2019-09-24 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| CA2741125A1 (en) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| WO2010051206A1 (en) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| EP2370427A1 (en) | 2008-12-02 | 2011-10-05 | Glaxo Group Limited | N-{[(ir,4s,6r-3-(2-pyridinylcarbonyl)-3-azabicyclo [4.1.0]hept-4-yl]methyl}-2-heteroarylamine derivatives and uses thereof |
| GB0823467D0 (en) | 2008-12-23 | 2009-01-28 | Glaxo Group Ltd | Novel Compounds |
| EA201171293A1 (ru) | 2009-04-24 | 2012-05-30 | Глэксо Груп Лимитед | 3-азабицикло[4.1.0]гептаны, применяемые в качестве антагонистов орексина |
| US20120149711A1 (en) | 2009-08-24 | 2012-06-14 | Glaxo Group Limited | Piperidine derivatives used as orexin antagonists |
| JP2013502447A (ja) | 2009-08-24 | 2013-01-24 | グラクソ グループ リミテッド | 睡眠障害の治療のためのオレキシン受容体アンタゴニストとしての５−メチル−ピペリジン誘導体 |
| US8895596B2 (en) | 2010-02-25 | 2014-11-25 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| WO2012089607A1 (en) | 2010-12-28 | 2012-07-05 | Glaxo Group Limited | Novel compounds with a 3a-azabicyclo [4.1.0] heptane core acting on orexin receptors |
| WO2012089606A1 (en) | 2010-12-28 | 2012-07-05 | Glaxo Group Limited | Azabicyclo [4.1.0] hept - 4 - yl derivatives as human orexin receptor antagonists |
| KR20150075120A (ko) | 2011-02-25 | 2015-07-02 | 머크 샤프 앤드 돔 코포레이션 | 항당뇨병제로서 유용한 신규 시클릭 아자벤즈이미다졸 유도체 |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| NZ628491A (en) | 2012-02-07 | 2016-06-24 | Eolas Therapeutics Inc | Substituted prolines / piperidines as orexin receptor antagonists |
| CA2873341C (en) | 2012-06-04 | 2018-01-02 | Actelion Pharmaceuticals Ltd | Benzimidazole-proline derivatives |
| EP2880028B1 (en) | 2012-08-02 | 2020-09-30 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| AU2013328301A1 (en) | 2012-10-10 | 2015-05-28 | Actelion Pharmaceuticals Ltd | Orexin receptor antagonists which are [ortho bi (hetero-)aryl]-[2-(meta bi (hetero-)aryl)-pyrrolidin-1-yl]-methanone derivatives |
| EP2958562B1 (en) | 2013-02-22 | 2025-09-10 | Merck Sharp & Dohme LLC | Antidiabetic bicyclic compounds |
| EP2970241A1 (en) | 2013-03-12 | 2016-01-20 | Actelion Pharmaceuticals Ltd. | Azetidine amide derivatives as orexin receptor antagonists |
| EP2970119B1 (en) | 2013-03-14 | 2021-11-03 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| HK1220696A1 (zh) | 2013-03-15 | 2017-05-12 | Bausch Health Ireland Limited | 鸟苷酸环化酶激动剂及其用途 |
| KR102272746B1 (ko) | 2013-06-05 | 2021-07-08 | 보슈 헬스 아일랜드 리미티드 | 구아닐레이트 사이클라제 c의 초순수 작용제, 및 이의 제조 및 사용 방법 |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| UA119151C2 (uk) | 2013-12-03 | 2019-05-10 | Ідорсія Фармасьютікалз Лтд | КРИСТАЛІЧНА СОЛЬОВА ФОРМА (S)-(2-(6-ХЛОР-7-МЕТИЛ-1H-БЕНЗО[d]ІМІДАЗОЛ-2-ІЛ)-2-МЕТИЛПІРОЛІДИН-1-ІЛ)(5-МЕТОКСИ-2-(2H-1,2,3-ТРИАЗОЛ-2-ІЛ)ФЕНІЛ)МЕТАНОНУ ЯК АНТАГОНІСТ ОРЕКСИНОВОГО РЕЦЕПТОРА |
| UA119549C2 (uk) | 2013-12-03 | 2019-07-10 | Ідорсія Фармасьютікалз Лтд | КРИСТАЛІЧНА ФОРМА (S)-(2-(6-ХЛОР-7-МЕТИЛ-1H-БЕНЗО[d]ІМІДАЗОЛ-2-ІЛ)-2-МЕТИЛПІРОЛІДИН-1-ІЛ)(5-МЕТОКСИ-2-(2H-1,2,3-ТРИАЗОЛ-2-ІЛ)ФЕНІЛ)МЕТАНОНУ ТА ЇЇ ЗАСТОСУВАННЯ ЯК АНТАГОНІСТА ОРЕКСИНОВОГО РЕЦЕПТОРА |
| MX366642B (es) | 2013-12-04 | 2019-07-17 | Idorsia Pharmaceuticals Ltd | Uso de derivados de bencimidazol-prolina. |
| ES2901418T3 (es) | 2014-08-13 | 2022-03-22 | Eolas Therapeutics Inc | Difluoropirrolidinas como moduladores del receptor de orexina |
| DK3414241T3 (da) | 2016-02-12 | 2022-08-01 | Astrazeneca Ab | Halogensubstituerede piperidiner som orexinreceptormodulatorer |
| WO2017194548A1 (en) | 2016-05-10 | 2017-11-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory diseases |
| WO2018106518A1 (en) | 2016-12-06 | 2018-06-14 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| EP3558298A4 (en) | 2016-12-20 | 2020-08-05 | Merck Sharp & Dohme Corp. | ANTIDIABETIC SPIROCHROMAN COMPOUNDS |
| WO2020007964A1 (en) | 2018-07-05 | 2020-01-09 | Idorsia Pharmaceuticals Ltd | 2-(2-azabicyclo[3.1.0]hexan-1-yl)-1h-benzimidazole derivatives |
| WO2020099511A1 (en) | 2018-11-14 | 2020-05-22 | Idorsia Pharmaceuticals Ltd | Benzimidazole-2-methyl-morpholine derivatives |
| EP3972588A4 (en) | 2019-06-04 | 2023-05-31 | Hager Biosciences, LLC | IMIDAZOL DERIVATIVES, COMPOSITIONS AND METHODS AS OREXIN ANTAGONISTS |
| WO2023218023A1 (en) | 2022-05-13 | 2023-11-16 | Idorsia Pharmaceuticals Ltd | Thiazoloaryl-methyl substituted cyclic hydrazine-n-carboxamide derivatives |
| GB202311280D0 (en) * | 2023-07-21 | 2023-09-06 | Bial Portela & Ca Sa | Orexin receptor antagonists |
| GB202311281D0 (en) * | 2023-07-21 | 2023-09-06 | Bial Portela & Ca Sa | Orexin receptor antagonists |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3621775A1 (de) * | 1986-03-13 | 1988-01-07 | Thomae Gmbh Dr K | Neue substituierte thiazole und oxazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| US4870074A (en) * | 1986-04-30 | 1989-09-26 | Dainippon Pharmaceutical Co., Ltd. | Substituted benzamide derivatives, for enhancing gastrointestinal motility |
| GB8813714D0 (en) * | 1988-06-09 | 1988-07-13 | Glaxo Group Ltd | Chemical compounds |
| US5719147A (en) * | 1992-06-29 | 1998-02-17 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
| ES2231158T3 (es) | 1999-02-12 | 2005-05-16 | Smithkline Beecham Plc | Derivados y fenil urea y fenil tiourea. |
| WO2000047577A1 (en) * | 1999-02-12 | 2000-08-17 | Smithkline Beecham Plc | Phenyl urea and phenyl thiourea derivatives as orexin receptor antagonists |
| FR2791346B3 (fr) * | 1999-03-25 | 2001-04-27 | Sanofi Sa | Nouveaux derives de morpholine, procede pour leur preparation et compositions pharmaceutiques les contenant |
| US6635661B2 (en) * | 2000-05-25 | 2003-10-21 | Sepracor Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| US6677332B1 (en) * | 1999-05-25 | 2004-01-13 | Sepracor, Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| AU6011301A (en) * | 2000-03-14 | 2001-09-24 | Actelion Pharmaceuticals Ltd | 1,2,3,4-tetrahydroisoquinoline derivatives |
| EP1289955B1 (en) * | 2000-06-16 | 2005-04-13 | Smithkline Beecham Plc | Piperidines for use as orexin receptor antagonists |
| IL155093A0 (en) * | 2000-09-29 | 2003-10-31 | Glaxo Group Ltd | Morpholin-acetamide derivatives for the treatment on inflammatory diseases |
| GB0130335D0 (en) * | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
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2001
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- 2001-11-22 ES ES01994716T patent/ES2234929T3/es not_active Expired - Lifetime
- 2001-11-22 DE DE60108420T patent/DE60108420T2/de not_active Expired - Lifetime
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- 2001-11-22 EP EP01994716A patent/EP1353918B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002044172A1 (en) | 2002-06-06 |
| EP1353918B1 (en) | 2005-01-12 |
| JP4246490B2 (ja) | 2009-04-02 |
| US6943160B2 (en) | 2005-09-13 |
| DE60108420T2 (de) | 2005-12-22 |
| DE60108420D1 (en) | 2005-02-17 |
| AU2002224885A1 (en) | 2002-06-11 |
| JP2004521087A (ja) | 2004-07-15 |
| ATE286897T1 (de) | 2005-01-15 |
| US20040058921A1 (en) | 2004-03-25 |
| EP1353918A1 (en) | 2003-10-22 |
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