CA3031100A1 - Macrocycle kinase inhibitors - Google Patents
Macrocycle kinase inhibitors Download PDFInfo
- Publication number
- CA3031100A1 CA3031100A1 CA3031100A CA3031100A CA3031100A1 CA 3031100 A1 CA3031100 A1 CA 3031100A1 CA 3031100 A CA3031100 A CA 3031100A CA 3031100 A CA3031100 A CA 3031100A CA 3031100 A1 CA3031100 A1 CA 3031100A1
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- CA
- Canada
- Prior art keywords
- alkyl
- cycloalkyl
- compound
- nhs
- membered heterocycloalkyl
- 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.)
- Pending
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- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 229960003862 vemurafenib Drugs 0.000 description 1
- GPXBXXGIAQBQNI-UHFFFAOYSA-N vemurafenib Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=CC(Cl)=CC=2)=C1F GPXBXXGIAQBQNI-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
Classifications
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- 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
- C07D498/12—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 three hetero rings
- C07D498/18—Bridged systems
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
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- 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
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- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- 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
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- 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
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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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US201662367886P | 2016-07-28 | 2016-07-28 | |
| US62/367,886 | 2016-07-28 | ||
| PCT/US2017/044214 WO2018022911A1 (en) | 2016-07-28 | 2017-07-27 | Macrocycle kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3031100A1 true CA3031100A1 (en) | 2018-02-01 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3031100A Pending CA3031100A1 (en) | 2016-07-28 | 2017-07-27 | Macrocycle kinase inhibitors |
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| EP (1) | EP3490564A4 (enExample) |
| JP (1) | JP2019527230A (enExample) |
| KR (1) | KR20190034225A (enExample) |
| CN (1) | CN109715165A (enExample) |
| AU (1) | AU2017302019A1 (enExample) |
| BR (1) | BR112019001607A2 (enExample) |
| CA (1) | CA3031100A1 (enExample) |
| IL (1) | IL264395A (enExample) |
| MX (1) | MX2019001125A (enExample) |
| RU (1) | RU2019105587A (enExample) |
| SG (1) | SG11201900163PA (enExample) |
| TW (1) | TW201815799A (enExample) |
| WO (1) | WO2018022911A1 (enExample) |
| ZA (1) | ZA201901034B (enExample) |
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| SG10202000191YA (en) | 2014-01-24 | 2020-03-30 | Turning Point Therapeutics Inc | Diaryl macrocycles as modulators of protein kinases |
| JP6871903B2 (ja) | 2015-07-02 | 2021-05-19 | ターニング・ポイント・セラピューティクス・インコーポレイテッドＴｕｒｎｉｎｇ Ｐｏｉｎｔ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | プロテインキナーゼのモジュレーターとしてのキラルジアリール大環状分子 |
| LT3733187T (lt) | 2015-07-21 | 2024-12-10 | Turning Point Therapeutics, Inc. | Chiralinis diarilo makrociklas ir jo panaudojimas vėžio gydymui |
| SG11201900163PA (en) | 2016-07-28 | 2019-02-27 | Tp Therapeutics Inc | Macrocycle kinase inhibitors |
| TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
| SMT202400343T1 (it) | 2017-07-28 | 2024-11-15 | Turning Point Therapeutics Inc | Composti macrociclici e loro usi |
| CN109516999B (zh) * | 2017-11-01 | 2021-08-17 | 郑州泰基鸿诺医药股份有限公司 | 用作蛋白质激酶调节剂的化合物及其应用 |
| HUE060711T2 (hu) | 2017-12-19 | 2023-04-28 | Turning Point Therapeutics Inc | Makrociklusos vegyületek betegségek kezelésére |
| JP2021519297A (ja) | 2018-03-28 | 2021-08-10 | フォチョン・ファーマシューティカルズ・リミテッドＦｏｃｈｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｌｔｄ． | Ｔｒｋキナーゼ阻害剤としての大環状化合物 |
| US12129258B2 (en) | 2018-04-25 | 2024-10-29 | Primegene (Beijing) Co., Ltd | Diaryl macrocyclic compound and pharmaceutical composition, and use thereof |
| KR102612513B1 (ko) | 2018-07-31 | 2023-12-12 | 록쏘 온콜로지, 인코포레이티드 | (s)-5-아미노-3-(4-((5-플루오로-2-메톡시벤즈아미도)메틸)페닐)-1-(1,1,1-트리플루오로프로판-2-일)-1h-피라졸-4-카르복스아미드의 분무-건조된 분산물 및 제제 |
| SI3870579T1 (sl) | 2018-10-22 | 2025-03-31 | Alumis Inc. | Inhibitorji tyk2 in njihova uporaba |
| US11780842B2 (en) * | 2019-03-26 | 2023-10-10 | Ventyx Biosciences, Inc. | TYK2 pseudokinase ligands |
| EP3974434B1 (en) | 2019-05-21 | 2025-11-19 | Zhejiang Hisun Pharmaceutical Co., Ltd. | Macrolide derivatives, preparation method and application thereof |
| CN113773335B (zh) * | 2019-06-21 | 2024-12-03 | 成都海博为药业有限公司 | 一种作为蛋白质激酶抑制剂的化合物及其制备方法和用途 |
| WO2021027503A1 (zh) * | 2019-08-12 | 2021-02-18 | 罗欣药业(上海)有限公司 | 三环类化合物、其制备方法、中间体及应用 |
| EP4041241A4 (en) | 2019-09-27 | 2023-09-06 | Disc Medicine, Inc. | METHODS OF TREATING MYELOFIBROSIS AND ASSOCIATED CONDITIONS |
| CN115397514A (zh) * | 2020-03-02 | 2022-11-25 | 特普医药公司 | 大环化合物的治疗用途 |
| KR20230012539A (ko) | 2020-05-13 | 2023-01-26 | 디스크 메디슨, 인크. | 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체 |
| EP4163283A1 (en) * | 2020-06-04 | 2023-04-12 | Scinnohub Pharmaceutical Co., Ltd | Compound having macrocyclic structure and use thereof |
| WO2022171139A1 (zh) * | 2021-02-10 | 2022-08-18 | 北京国鸿生物医药科技有限公司 | 一种巨环化合物、药物组合物以及其用途 |
| CN113354548A (zh) * | 2021-04-12 | 2021-09-07 | 常熟耐素生物材料科技有限公司 | 一种基于六亚甲基四胺的植物多烯酚醛胺环氧固化剂及其制备方法 |
| CN116063326B (zh) * | 2021-11-02 | 2025-08-05 | 赛诺哈勃药业（成都）有限公司 | 作为蛋白激酶调节剂的含氨基大环化合物 |
| WO2023208244A1 (zh) * | 2022-04-29 | 2023-11-02 | 南京明德新药研发有限公司 | 大环类化合物及其应用 |
| WO2025010294A2 (en) * | 2023-07-03 | 2025-01-09 | Blossomhill Therapeutics, Inc. | Macrocyclic compounds and use as tyk2 inhibitors |
Family Cites Families (29)
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| ES2149869T3 (es) | 1993-03-25 | 2000-11-16 | Upjohn Co | Derivados de indol sustituidos por formil o ciano con actividad dopominergica. |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
| EA201100450A1 (ru) * | 2008-09-08 | 2011-10-31 | Мерк Патент Гмбх | Макроциклические пирамидины в качестве ингибиторов протеинкиназы |
| RS53350B (sr) | 2008-09-22 | 2014-10-31 | Array Biopharma, Inc. | Supstituisana jedinjenja imidazo[1,2-b]piridazina kao inhibitori trk kinaze |
| EP2350071B1 (en) | 2008-10-22 | 2014-01-08 | Array Biopharma, Inc. | SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS |
| CN102271515B (zh) | 2008-10-31 | 2014-07-02 | 健泰科生物技术公司 | 吡唑并嘧啶jak抑制剂化合物和方法 |
| PL3205654T3 (pl) | 2010-05-20 | 2019-08-30 | Array Biopharma, Inc. | Związki makrocykliczne jako inhibitory kinazy TRK |
| US8757434B2 (en) * | 2010-07-01 | 2014-06-24 | The Coca-Cola Company | Merchandiser |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| EP2508607A1 (en) | 2011-04-07 | 2012-10-10 | Helmholtz-Zentrum für Infektionsforschung GmbH | Medicament for liver regeneration and for treatment of liver failure |
| RU2598840C2 (ru) * | 2011-05-19 | 2016-09-27 | Фундасион Сентро Насиональ Де Инвестигасионес Онколохикас Карлос Iii | Новые соединения |
| WO2013001310A1 (en) | 2011-06-30 | 2013-01-03 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Macrocyclic compounds and their use as cdk8 inhibitors |
| JP2014521750A (ja) | 2011-08-19 | 2014-08-28 | メルク・シャープ・アンド・ドーム・コーポレーション | マクロラクタムを調製するための方法および中間体 |
| KR20140078710A (ko) | 2011-09-30 | 2014-06-25 | 온코디자인 에스.에이. | 거대고리 flt3 키나제 억제제 |
| UA113186C2 (xx) * | 2011-09-30 | 2016-12-26 | Макроциклічні інгібітори lrrk2 кінази | |
| HUE034118T2 (en) | 2012-03-06 | 2018-01-29 | Pfizer | Macrocyclic derivatives for the treatment of proliferative diseases |
| WO2013134228A1 (en) | 2012-03-09 | 2013-09-12 | Lexicon Pharmaceuticals, Inc. | PYRAZOLO[1,5-a]PYRIMIDINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE |
| EP2822559B1 (en) | 2012-03-09 | 2018-05-02 | Lexicon Pharmaceuticals, Inc. | Imidazo[1,2-b]pyridazine-based compounds, compositions comprising them, and uses thereof |
| GB201205669D0 (en) | 2012-03-30 | 2012-05-16 | Agency Science Tech & Res | Bicyclic heterocyclic derivatives as mnk2 and mnk2 modulators and uses thereof |
| AU2014230111A1 (en) * | 2013-03-15 | 2015-10-29 | Oncodesign S.A | Macrocyclic RIP2 kinase inhibitors |
| CN104513253A (zh) * | 2013-10-01 | 2015-04-15 | 南京波尔泰药业科技有限公司 | 用于治疗增殖性疾病的大环化合物 |
| SG10202000191YA (en) | 2014-01-24 | 2020-03-30 | Turning Point Therapeutics Inc | Diaryl macrocycles as modulators of protein kinases |
| JP6871903B2 (ja) | 2015-07-02 | 2021-05-19 | ターニング・ポイント・セラピューティクス・インコーポレイテッドＴｕｒｎｉｎｇ Ｐｏｉｎｔ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | プロテインキナーゼのモジュレーターとしてのキラルジアリール大環状分子 |
| RU2765181C2 (ru) | 2015-07-06 | 2022-01-26 | Тёрнинг Поинт Терапьютикс, Инк. | Полиморфная форма диарильного макроцикла |
| LT3733187T (lt) | 2015-07-21 | 2024-12-10 | Turning Point Therapeutics, Inc. | Chiralinis diarilo makrociklas ir jo panaudojimas vėžio gydymui |
| SG11201900163PA (en) | 2016-07-28 | 2019-02-27 | Tp Therapeutics Inc | Macrocycle kinase inhibitors |
| TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
| SMT202400343T1 (it) | 2017-07-28 | 2024-11-15 | Turning Point Therapeutics Inc | Composti macrociclici e loro usi |
-
2017
- 2017-07-27 SG SG11201900163PA patent/SG11201900163PA/en unknown
- 2017-07-27 AU AU2017302019A patent/AU2017302019A1/en not_active Abandoned
- 2017-07-27 TW TW106125249A patent/TW201815799A/zh unknown
- 2017-07-27 KR KR1020197003927A patent/KR20190034225A/ko not_active Ceased
- 2017-07-27 JP JP2019504675A patent/JP2019527230A/ja active Pending
- 2017-07-27 MX MX2019001125A patent/MX2019001125A/es unknown
- 2017-07-27 CA CA3031100A patent/CA3031100A1/en active Pending
- 2017-07-27 EP EP17835284.5A patent/EP3490564A4/en not_active Withdrawn
- 2017-07-27 BR BR112019001607-4A patent/BR112019001607A2/pt not_active Application Discontinuation
- 2017-07-27 RU RU2019105587A patent/RU2019105587A/ru not_active Application Discontinuation
- 2017-07-27 US US16/320,589 patent/US10689400B2/en active Active
- 2017-07-27 CN CN201780056515.5A patent/CN109715165A/zh active Pending
- 2017-07-27 WO PCT/US2017/044214 patent/WO2018022911A1/en not_active Ceased
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2019
- 2019-01-22 IL IL264395A patent/IL264395A/en unknown
- 2019-02-18 ZA ZA2019/01034A patent/ZA201901034B/en unknown
Also Published As
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| US20190169208A1 (en) | 2019-06-06 |
| US10689400B2 (en) | 2020-06-23 |
| WO2018022911A1 (en) | 2018-02-01 |
| ZA201901034B (en) | 2021-06-30 |
| BR112019001607A2 (pt) | 2019-04-30 |
| SG11201900163PA (en) | 2019-02-27 |
| IL264395A (en) | 2019-02-28 |
| EP3490564A4 (en) | 2020-02-26 |
| MX2019001125A (es) | 2019-06-12 |
| CN109715165A (zh) | 2019-05-03 |
| AU2017302019A1 (en) | 2019-02-07 |
| RU2019105587A3 (enExample) | 2020-11-18 |
| TW201815799A (zh) | 2018-05-01 |
| RU2019105587A (ru) | 2020-08-28 |
| JP2019527230A (ja) | 2019-09-26 |
| KR20190034225A (ko) | 2019-04-01 |
| EP3490564A1 (en) | 2019-06-05 |
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