CY1110295T1 - Trans-9,10-δεϋδροεποθιλονη c και d, αναλογα αυτων και μεθοδοι παρασκευης - Google Patents
Trans-9,10-δεϋδροεποθιλονη c και d, αναλογα αυτων και μεθοδοι παρασκευηςInfo
- Publication number
- CY1110295T1 CY1110295T1 CY20101100250T CY101100250T CY1110295T1 CY 1110295 T1 CY1110295 T1 CY 1110295T1 CY 20101100250 T CY20101100250 T CY 20101100250T CY 101100250 T CY101100250 T CY 101100250T CY 1110295 T1 CY1110295 T1 CY 1110295T1
- Authority
- CY
- Cyprus
- Prior art keywords
- trans
- dehydrophothyline
- analogues
- preparation
- methods
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 abstract 1
Classifications
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- 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
- A61P25/28—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
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42535202P | 2002-11-07 | 2002-11-07 | |
| US47374303P | 2003-05-27 | 2003-05-27 | |
| EP03768730A EP1562941B1 (en) | 2002-11-07 | 2003-11-07 | Trans-9,10-dehydroepothilone c and d, analogs thereof and methos of making the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CY1110295T1 true CY1110295T1 (el) | 2015-01-14 |
Family
ID=32314587
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CY20101100250T CY1110295T1 (el) | 2002-11-07 | 2010-03-19 | Trans-9,10-δεϋδροεποθιλονη c και d, αναλογα αυτων και μεθοδοι παρασκευης |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US20040152708A1 (OSRAM) |
| EP (3) | EP2135868A1 (OSRAM) |
| JP (3) | JP4641941B2 (OSRAM) |
| KR (2) | KR100996996B1 (OSRAM) |
| AT (1) | ATE452888T1 (OSRAM) |
| AU (1) | AU2003291337B2 (OSRAM) |
| CA (1) | CA2505368C (OSRAM) |
| CY (1) | CY1110295T1 (OSRAM) |
| DE (1) | DE60330703D1 (OSRAM) |
| DK (1) | DK1562941T3 (OSRAM) |
| ES (2) | ES2336911T3 (OSRAM) |
| PT (1) | PT1562941E (OSRAM) |
| SI (1) | SI1562941T1 (OSRAM) |
| WO (1) | WO2004043954A2 (OSRAM) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4579351B2 (ja) | 1996-12-03 | 2010-11-10 | スローン−ケッタリング インスティトュート フォア キャンサー リサーチ | エポチロンの合成とその中間体及びその類似物並びにその使用 |
| US8618085B2 (en) * | 2000-04-28 | 2013-12-31 | Koasn Biosciences Incorporated | Therapeutic formulations of desoxyepothilones |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| CA2496477C (en) | 2002-08-23 | 2012-10-16 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US7384964B2 (en) * | 2002-08-23 | 2008-06-10 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| CN101088998A (zh) * | 2002-11-07 | 2007-12-19 | 科桑生物科学公司 | 反式－9,10－脱氢埃坡霉素c和d,其类似物以及制备这些化合物的方法 |
| KR100996996B1 (ko) * | 2002-11-07 | 2010-11-25 | 코산 바이오사이언시즈, 인코포레이티드 | 트랜스-9,10-디히드로에포틸론 ｃ 및 ｄ, 그것의 유사체 및 그것의 제조 방법 |
| RU2005133199A (ru) * | 2003-03-28 | 2006-02-10 | Козан Байосайенсиз, Инк. (Us) | Устройства, способы и композиции для предупреждения рестеноза |
| WO2005034964A1 (en) * | 2003-10-09 | 2005-04-21 | Kosan Biosciences, Inc. | Therapeutic formulations |
| US20050215604A1 (en) * | 2004-03-26 | 2005-09-29 | Kosan Biosciences, Inc. | Combination therapies with epothilones and carboplatin |
| US7981998B2 (en) * | 2006-12-14 | 2011-07-19 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| CN105061577A (zh) * | 2006-12-14 | 2015-11-18 | 爱勒让治疗公司 | 双巯基大环化系统 |
| PT2118123E (pt) | 2007-01-31 | 2016-02-10 | Harvard College | Péptidos de p53 estabilizados e suas utilizações |
| CN109627287A (zh) * | 2007-02-23 | 2019-04-16 | 爱勒让治疗公司 | 三唑大环系统 |
| JP5631201B2 (ja) | 2007-03-28 | 2014-11-26 | プレジデント アンド フェローズ オブ ハーバード カレッジ | ステッチングされたポリペプチド |
| US8030503B2 (en) | 2007-05-11 | 2011-10-04 | Kosan Biosciences Incorporated | Process for the preparation of epothilones |
| WO2008141234A2 (en) * | 2007-05-11 | 2008-11-20 | Kosan Biosciences Incorporated | Methods of making epothilones |
| EP2376100B1 (en) | 2009-01-14 | 2017-10-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2011038049A1 (en) | 2009-09-22 | 2011-03-31 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| MX355543B (es) | 2010-08-13 | 2018-04-20 | Aileron Therapeutics Inc Star | Macrociclos peptidomiméticos. |
| TWI643868B (zh) | 2011-10-18 | 2018-12-11 | 艾利倫治療公司 | 擬肽巨環化合物 |
| EP2819688A4 (en) | 2012-02-15 | 2015-10-28 | Aileron Therapeutics Inc | PEPTIDOMIMETIC MACROCYCLES CROSS-LINKED WITH TRIAZOLE AND THIOETHER |
| SG11201404648PA (en) | 2012-02-15 | 2014-09-26 | Aileron Therapeutics Inc | Peptidomimetic macrocycles |
| CA2776178A1 (en) | 2012-04-05 | 2013-10-05 | Hydro-Quebec | Ionic compounds |
| KR20150082307A (ko) | 2012-11-01 | 2015-07-15 | 에일러론 테라퓨틱스 인코포레이티드 | 이치환 아미노산 및 이의 제조 및 사용 방법 |
| SG11201702223UA (en) | 2014-09-24 | 2017-04-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| EP3197477A4 (en) | 2014-09-24 | 2018-07-04 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
| KR20170129879A (ko) | 2015-03-20 | 2017-11-27 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티드모방 거대고리 및 이의 용도 |
| US10059741B2 (en) | 2015-07-01 | 2018-08-28 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| JP2018528217A (ja) | 2015-09-10 | 2018-09-27 | エルロン・セラピューティクス・インコーポレイテッドＡｉｌｅｒｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | Ｍｃｌ−１のモジュレーターとしてのペプチド模倣大環状分子 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT706373E (pt) | 1992-03-23 | 2000-11-30 | Univ Georgetown | Taxol encapsulado num liposoma e um metodo |
| WO1994026254A1 (en) | 1993-05-17 | 1994-11-24 | The Liposome Company, Inc. | Incorporation of taxol into liposomes and gels |
| US5415869A (en) | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
| US5662883A (en) | 1995-01-10 | 1997-09-02 | Nanosystems L.L.C. | Microprecipitation of micro-nanoparticulate pharmaceutical agents |
| US5534270A (en) | 1995-02-09 | 1996-07-09 | Nanosystems Llc | Method of preparing stable drug nanoparticles |
| US5510118A (en) | 1995-02-14 | 1996-04-23 | Nanosystems Llc | Process for preparing therapeutic compositions containing nanoparticles |
| EP0932399B1 (en) | 1996-03-12 | 2006-01-04 | PG-TXL Company, L.P. | Water soluble paclitaxel prodrugs |
| US6458373B1 (en) | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| KR20080016756A (ko) | 1998-02-05 | 2008-02-21 | 노파르티스 아게 | 유기화합물 함유 조성물 |
| US6596875B2 (en) * | 2000-02-07 | 2003-07-22 | James David White | Method for synthesizing epothilones and epothilone analogs |
| DE19907480A1 (de) * | 1999-02-11 | 2000-08-17 | Schering Ag | Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung |
| DE19954229A1 (de) * | 1999-11-04 | 2001-05-10 | Schering Ag | Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung |
| US6156373A (en) | 1999-05-03 | 2000-12-05 | Scimed Life Systems, Inc. | Medical device coating methods and devices |
| AU5273200A (en) | 1999-05-24 | 2000-12-12 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| GB9918429D0 (en) | 1999-08-04 | 1999-10-06 | Novartis Ag | Organic compounds |
| AU2001295195B2 (en) | 2000-04-28 | 2007-02-01 | Kosan Biosciences, Inc. | Myxococcus host cells for the production of epothilones |
| AU2001266583A1 (en) * | 2000-05-26 | 2001-12-11 | Kosan Biosciences, Inc. | Epothilone derivatives and methods for making and using the same |
| US6906188B2 (en) * | 2001-04-30 | 2005-06-14 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregon State University | Method for synthesizing epothilones and epothilone analogs |
| US20030176368A1 (en) * | 2001-09-06 | 2003-09-18 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US7649006B2 (en) * | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US6921769B2 (en) * | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| CA2496477C (en) * | 2002-08-23 | 2012-10-16 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| KR100996996B1 (ko) * | 2002-11-07 | 2010-11-25 | 코산 바이오사이언시즈, 인코포레이티드 | 트랜스-9,10-디히드로에포틸론 ｃ 및 ｄ, 그것의 유사체 및 그것의 제조 방법 |
-
2003
- 2003-11-07 KR KR1020107000780A patent/KR100996996B1/ko not_active Expired - Fee Related
- 2003-11-07 AT AT03768730T patent/ATE452888T1/de active
- 2003-11-07 ES ES03768730T patent/ES2336911T3/es not_active Expired - Lifetime
- 2003-11-07 AU AU2003291337A patent/AU2003291337B2/en not_active Ceased
- 2003-11-07 ES ES09012671T patent/ES2436296T3/es not_active Expired - Lifetime
- 2003-11-07 KR KR1020057008039A patent/KR100966667B1/ko not_active Expired - Fee Related
- 2003-11-07 JP JP2005507102A patent/JP4641941B2/ja not_active Expired - Fee Related
- 2003-11-07 EP EP09012860A patent/EP2135868A1/en not_active Withdrawn
- 2003-11-07 CA CA2505368A patent/CA2505368C/en not_active Expired - Fee Related
- 2003-11-07 EP EP09012671.5A patent/EP2135867B1/en not_active Expired - Lifetime
- 2003-11-07 EP EP03768730A patent/EP1562941B1/en not_active Expired - Lifetime
- 2003-11-07 US US10/703,404 patent/US20040152708A1/en not_active Abandoned
- 2003-11-07 SI SI200331732T patent/SI1562941T1/sl unknown
- 2003-11-07 PT PT03768730T patent/PT1562941E/pt unknown
- 2003-11-07 DE DE60330703T patent/DE60330703D1/de not_active Expired - Lifetime
- 2003-11-07 DK DK03768730.8T patent/DK1562941T3/da active
- 2003-11-07 WO PCT/US2003/035411 patent/WO2004043954A2/en not_active Ceased
-
2008
- 2008-07-11 US US12/172,174 patent/US20090186927A1/en not_active Abandoned
-
2010
- 2010-03-19 CY CY20101100250T patent/CY1110295T1/el unknown
- 2010-10-08 JP JP2010228356A patent/JP5679757B2/ja not_active Expired - Fee Related
-
2013
- 2013-07-16 JP JP2013147528A patent/JP2013213054A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013213054A (ja) | 2013-10-17 |
| DE60330703D1 (de) | 2010-02-04 |
| EP1562941B1 (en) | 2009-12-23 |
| AU2003291337B2 (en) | 2010-09-09 |
| EP2135868A1 (en) | 2009-12-23 |
| ES2436296T3 (es) | 2013-12-30 |
| KR20050084959A (ko) | 2005-08-29 |
| CA2505368C (en) | 2011-09-20 |
| JP4641941B2 (ja) | 2011-03-02 |
| PT1562941E (pt) | 2010-01-25 |
| DK1562941T3 (da) | 2010-04-19 |
| EP2135867A1 (en) | 2009-12-23 |
| ES2336911T3 (es) | 2010-04-19 |
| JP2006510743A (ja) | 2006-03-30 |
| AU2003291337A1 (en) | 2004-06-03 |
| KR100966667B1 (ko) | 2010-06-29 |
| JP2011006480A (ja) | 2011-01-13 |
| US20040152708A1 (en) | 2004-08-05 |
| EP2135867B1 (en) | 2013-09-25 |
| WO2004043954A3 (en) | 2004-11-18 |
| KR100996996B1 (ko) | 2010-11-25 |
| WO2004043954A2 (en) | 2004-05-27 |
| CA2505368A1 (en) | 2004-05-27 |
| EP1562941A2 (en) | 2005-08-17 |
| KR20100018075A (ko) | 2010-02-16 |
| JP5679757B2 (ja) | 2015-03-04 |
| SI1562941T1 (sl) | 2010-05-31 |
| ATE452888T1 (de) | 2010-01-15 |
| US20090186927A1 (en) | 2009-07-23 |
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