DE60332629D1 - Phenyl-(4-(3-phenyl-1h-pyrazol-4-yl)-pyrimidin-2-yi)aminderivate - Google Patents
Phenyl-(4-(3-phenyl-1h-pyrazol-4-yl)-pyrimidin-2-yi)aminderivateInfo
- Publication number
- DE60332629D1 DE60332629D1 DE60332629T DE60332629T DE60332629D1 DE 60332629 D1 DE60332629 D1 DE 60332629D1 DE 60332629 T DE60332629 T DE 60332629T DE 60332629 T DE60332629 T DE 60332629T DE 60332629 D1 DE60332629 D1 DE 60332629D1
- Authority
- DE
- Germany
- Prior art keywords
- phenyl
- pyrazol
- pyrimidin
- amine derivatives
- derivatives
- 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
- -1 PHENYL- (4- (3-phenyl-1H-pyrazol-4-yl) -pyrimidin-2-yl) amine Chemical class 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 2
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- GHIDSWLDHRXNQM-UHFFFAOYSA-N n-phenyl-4-(5-phenyl-1h-pyrazol-4-yl)pyrimidin-2-amine Chemical class N=1C=CC(C=2C(=NNC=2)C=2C=CC=CC=2)=NC=1NC1=CC=CC=C1 GHIDSWLDHRXNQM-UHFFFAOYSA-N 0.000 abstract 1
- 230000002062 proliferating effect Effects 0.000 abstract 1
Classifications
-
- 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
-
- 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
- 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
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0215844.2A GB0215844D0 (en) | 2002-07-09 | 2002-07-09 | Organic compounds |
| PCT/EP2003/007350 WO2004005282A1 (en) | 2002-07-09 | 2003-07-08 | PHENYL-[4-(3-PHENYL-1H-PYRAZOL-4-YL)-PYRIMIDIN-2-Yl)-AMINE DERIVATIVES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE60332629D1 true DE60332629D1 (de) | 2010-07-01 |
Family
ID=9940097
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60332629T Expired - Lifetime DE60332629D1 (de) | 2002-07-09 | 2003-07-08 | Phenyl-(4-(3-phenyl-1h-pyrazol-4-yl)-pyrimidin-2-yi)aminderivate |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7691855B2 (de) |
| EP (1) | EP1521749B8 (de) |
| JP (1) | JP4478016B2 (de) |
| CN (1) | CN1330643C (de) |
| AT (1) | ATE468332T1 (de) |
| AU (1) | AU2003249993A1 (de) |
| BR (1) | BR0312573A (de) |
| CA (1) | CA2491635A1 (de) |
| DE (1) | DE60332629D1 (de) |
| ES (1) | ES2346427T3 (de) |
| GB (1) | GB0215844D0 (de) |
| PT (1) | PT1521749E (de) |
| WO (1) | WO2004005282A1 (de) |
Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4377583B2 (ja) * | 2000-12-05 | 2009-12-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｃ−ｊｕｎｎ末端キナーゼ（ｊｎｋ）および他のタンパク質キナーゼのインヒビター |
| AR039241A1 (es) | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| US7154002B1 (en) | 2002-10-08 | 2006-12-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| US7250514B1 (en) | 2002-10-21 | 2007-07-31 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| EP1608628A2 (de) | 2003-03-17 | 2005-12-28 | Takeda San Diego, Inc. | Inhibitoren der histondeacetylase |
| GB0311274D0 (en) | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
| SI1660057T1 (sl) | 2003-08-27 | 2012-10-30 | Ophthotech Corp | Kombinirana terapija za zdravljenje okularnih neovaskularnih nepravilnosti |
| BRPI0506760A (pt) * | 2004-01-09 | 2007-05-22 | Novartis Ag | derivados de fenil-[4-(3-fenil-1h-pirazol-4-il)-pirimidin-2-il]-amina como inibidores de igf-ir |
| TW200528101A (en) | 2004-02-03 | 2005-09-01 | Astrazeneca Ab | Chemical compounds |
| CN101039919A (zh) * | 2004-10-13 | 2007-09-19 | 惠氏公司 | 经n－苯磺酰基取代的苯胺基嘧啶类似物 |
| US7855205B2 (en) | 2004-10-29 | 2010-12-21 | Janssen Pharmaceutica Nv | Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders |
| JO2596B1 (en) * | 2004-11-30 | 2011-02-27 | نوفارتيس ايه جي | Compositions include epothelones and tyrosine protein kinase inhibitors and their pharmaceutical uses |
| WO2006066133A2 (en) | 2004-12-16 | 2006-06-22 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| WO2006122319A2 (en) | 2005-05-11 | 2006-11-16 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| US7732475B2 (en) | 2005-07-14 | 2010-06-08 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| EP1912974A1 (de) * | 2005-07-30 | 2008-04-23 | AstraZeneca AB | Imidazolylpyrimidinverbindungen zur verwendung bei der behandlung von proliferativen erkrankungen |
| CN101277956A (zh) | 2005-09-30 | 2008-10-01 | 阿斯利康(瑞典)有限公司 | 具有抗细胞增殖活性的咪唑并【1，2-a】吡啶 |
| ME01312B (me) * | 2005-12-13 | 2013-12-20 | Incyte Corp | Heteroaril supstituirani pirol0[2,3-b]piridini i pirol0 [ 2,3-b]pirimidini kao inhibitori janus kinaze |
| CA2643066A1 (en) * | 2006-03-16 | 2007-09-20 | Pfizer Products Inc. | Pyrazole compounds |
| CN103739595A (zh) | 2006-10-02 | 2014-04-23 | Irm责任有限公司 | 作为蛋白激酶抑制剂的化合物和组合物 |
| US8338434B2 (en) * | 2007-03-29 | 2012-12-25 | Glaxosmithkline Llc | Inhibitors of Akt activity |
| SG182198A1 (en) | 2007-06-13 | 2012-07-30 | Incyte Corp | Salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile |
| US20100144756A1 (en) * | 2007-07-13 | 2010-06-10 | Bolea Christelle | Novel heteroaromatic derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors |
| CA2695114A1 (en) * | 2007-08-01 | 2009-02-05 | Pfizer Inc. | Pyrazole compounds and their use as raf inhibitors |
| CN101910152B (zh) | 2007-11-16 | 2014-08-06 | 因塞特公司 | 作为janus激酶抑制剂的4-吡唑基-n-芳基嘧啶-2-胺和4-吡唑基-n-杂芳基嘧啶-2-胺 |
| PT2231636E (pt) | 2007-12-07 | 2012-01-02 | Novartis Ag | Derivados de pirazole e a sua utilização a título de inibidores de quinases dependentes de ciclina |
| HUE030912T2 (en) * | 2008-02-15 | 2017-06-28 | Rigel Pharmaceuticals Inc | Pyrimidine-2-amine compounds and their use as inhibitors of yak kinases |
| JP2012518657A (ja) | 2009-02-25 | 2012-08-16 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 併用抗癌治療 |
| WO2010099363A1 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| EA025520B1 (ru) | 2009-05-22 | 2017-01-30 | Инсайт Холдингс Корпорейшн | N-(ГЕТЕРО)АРИЛПИРРОЛИДИНОВЫЕ ПРОИЗВОДНЫЕ ПИРАЗОЛ-4-ИЛ-ПИРРОЛО[2,3-d]ПИРИМИДИНОВ И ПИРРОЛ-3-ИЛ-ПИРРОЛО[2,3-d]ПИРИМИДИНОВ В КАЧЕСТВЕ ИНГИБИТОРОВ ЯНУС-КИНАЗЫ |
| EP3643312A1 (de) | 2009-05-22 | 2020-04-29 | Incyte Holdings Corporation | 3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]octan- oder heptannitril als jak-inhibitoren |
| EP2435436B1 (de) * | 2009-05-27 | 2014-07-30 | AbbVie Inc. | Pyrimidinhemmer der kinaseaktivität |
| AR078012A1 (es) | 2009-09-01 | 2011-10-05 | Incyte Corp | Derivados heterociclicos de las pirazol-4-il- pirrolo (2,3-d) pirimidinas como inhibidores de la quinasa janus |
| EP2308866A1 (de) * | 2009-10-09 | 2011-04-13 | Bayer CropScience AG | Phenylpyri(mi)dinylpyrazole und ihre Verwendung als Fungizide |
| JP5858484B2 (ja) | 2010-03-10 | 2016-02-10 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｊａｋ１阻害剤としてのピペリジン−４−イルアゼチジン誘導体 |
| EA202091303A3 (ru) | 2010-05-21 | 2021-05-31 | Инсайт Холдингс Корпорейшн | Композиция ингибитора jak для местного применения |
| HRP20160771T1 (hr) | 2010-06-04 | 2016-09-23 | F. Hoffmann - La Roche Ag | Derivati aminopirimidina kao modulatori za lrrk2 |
| AR083813A1 (es) | 2010-11-10 | 2013-03-27 | Hoffmann La Roche | Derivados de pirazol aminopirimidina como moduladores de lrrk2 |
| JP5917544B2 (ja) | 2010-11-19 | 2016-05-18 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｊａｋ阻害剤としての複素環置換ピロロピリジンおよびピロロピリミジン |
| CA2818542A1 (en) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| WO2012112674A2 (en) * | 2011-02-15 | 2012-08-23 | The Johns Hopkins University | Compounds and methods of use thereof for treating neurodegenerative disorders |
| JP2014519813A (ja) | 2011-04-25 | 2014-08-21 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 癌薬剤発見、診断、および治療におけるｅｍｔ遺伝子シグネチャーの使用 |
| MY165963A (en) | 2011-06-20 | 2018-05-18 | Incyte Holdings Corp | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors |
| TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物 |
| UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
| WO2013071232A1 (en) * | 2011-11-11 | 2013-05-16 | Beta Cat Pharmaceuticals, Llc | Compositions and methods for inhibition of tbl-1 binding to disease-associated molecules |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| US9193733B2 (en) | 2012-05-18 | 2015-11-24 | Incyte Holdings Corporation | Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors |
| DK2919766T3 (da) | 2012-11-15 | 2021-07-12 | Incyte Holdings Corp | Ruxolitinib-depotdosisformer |
| AR093579A1 (es) | 2012-11-21 | 2015-06-10 | Ptc Therapeutics Inc | Inhibidores de bmi-1 de pirimidina inversa sustituida |
| EP2964650B1 (de) | 2013-03-06 | 2018-12-05 | Incyte Holdings Corporation | Verfahren und zwischenprodukte zur herstellung eines jak-hemmers |
| EP3628373A1 (de) | 2013-07-12 | 2020-04-01 | IVERIC bio, Inc. | Verfahren zur behandlung oder prävention von augenerkrankungen |
| EP3030227B1 (de) | 2013-08-07 | 2020-04-08 | Incyte Corporation | Dosierungsformen mit anhaltender freisetzung für einen jak1-inhibitor |
| KR102232595B1 (ko) | 2013-08-30 | 2021-03-26 | 피티씨 테라퓨틱스, 인크. | 치환된 피리미딘 bmi-1 저해제 |
| US10584115B2 (en) | 2013-11-21 | 2020-03-10 | Ptc Therapeutics, Inc. | Substituted pyridine and pyrazine BMI-1 inhibitors |
| WO2015184305A1 (en) | 2014-05-30 | 2015-12-03 | Incyte Corporation | TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1 |
| US10376511B2 (en) * | 2015-08-04 | 2019-08-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Pyrazole pyrimidine derivative and uses thereof |
| TW201924683A (zh) | 2017-12-08 | 2019-07-01 | 美商英塞特公司 | 用於治療骨髓增生性贅瘤的低劑量組合療法 |
| AR114810A1 (es) | 2018-01-30 | 2020-10-21 | Incyte Corp | Procesos e intermedios para elaborar un inhibidor de jak |
| EA202092343A1 (ru) | 2018-03-30 | 2021-01-20 | Инсайт Корпорейшн | Лечение гнойного гидраденита с использованием ингибиторов jak |
| CN113164479A (zh) | 2018-08-17 | 2021-07-23 | Ptc医疗公司 | 用于治疗胰腺癌的方法 |
| PT3985000T (pt) * | 2019-06-28 | 2025-01-03 | Chengdu Zenitar Biomedical Tech Co Ltd | Derivado de pirimidina 2,4-dissubstituída, método de preparação para o mesmo e suas utilizações |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
| EP4329762A1 (de) * | 2021-04-28 | 2024-03-06 | Cornell University | Lösliche adenylylcyclase (sac)-inhibitoren und verwendungen davon |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL112290A (en) | 1994-01-12 | 1999-01-26 | Novartis Ag | Transformed aryl and the troiryl pyrimidines and herbicides containing them |
| US5559137A (en) | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
| US6514977B1 (en) * | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| EE9900527A (et) | 1997-05-22 | 2000-06-15 | G.D. Searle & Co. | Substitueeritud pürasoolid kui p38 kinaasi inhibiitorid |
| EP1023066A4 (de) | 1997-06-13 | 2001-05-23 | Smithkline Beecham Corp | Neue pyrazole- und pyrazoline- substituierte verbindung |
| WO2001012621A1 (en) | 1999-08-13 | 2001-02-22 | Vertex Pharmaceuticals Incorporated | INHIBITORS OF c-JUN N-TERMINAL KINASES (JNK) AND OTHER PROTEIN KINASES |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| CA2400447C (en) | 2000-02-17 | 2008-04-22 | Amgen Inc. | Kinase inhibitors |
| EP1261327B1 (de) | 2000-02-25 | 2005-04-27 | F.Hoffmann-La Roche Ag | Adenosin-rezeptor modulatoren |
| US7276510B2 (en) | 2000-05-08 | 2007-10-02 | Janssen Pharmaceutica, Inc. | HIV replication inhibitors |
| JP4377583B2 (ja) * | 2000-12-05 | 2009-12-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｃ−ｊｕｎｎ末端キナーゼ（ｊｎｋ）および他のタンパク質キナーゼのインヒビター |
| GB0129476D0 (en) | 2001-12-10 | 2002-01-30 | Syngenta Participations Ag | Organic compounds |
-
2002
- 2002-07-09 GB GBGB0215844.2A patent/GB0215844D0/en not_active Ceased
-
2003
- 2003-07-08 WO PCT/EP2003/007350 patent/WO2004005282A1/en active Application Filing
- 2003-07-08 CA CA002491635A patent/CA2491635A1/en not_active Abandoned
- 2003-07-08 JP JP2004518751A patent/JP4478016B2/ja not_active Expired - Lifetime
- 2003-07-08 AT AT03762663T patent/ATE468332T1/de not_active IP Right Cessation
- 2003-07-08 US US10/520,567 patent/US7691855B2/en not_active Expired - Fee Related
- 2003-07-08 BR BR0312573-4A patent/BR0312573A/pt not_active IP Right Cessation
- 2003-07-08 AU AU2003249993A patent/AU2003249993A1/en not_active Abandoned
- 2003-07-08 ES ES03762663T patent/ES2346427T3/es not_active Expired - Lifetime
- 2003-07-08 PT PT03762663T patent/PT1521749E/pt unknown
- 2003-07-08 EP EP03762663A patent/EP1521749B8/de not_active Expired - Lifetime
- 2003-07-08 DE DE60332629T patent/DE60332629D1/de not_active Expired - Lifetime
- 2003-07-08 CN CNB038163837A patent/CN1330643C/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1668610A (zh) | 2005-09-14 |
| ATE468332T1 (de) | 2010-06-15 |
| ES2346427T3 (es) | 2010-10-15 |
| GB0215844D0 (en) | 2002-08-14 |
| EP1521749A1 (de) | 2005-04-13 |
| EP1521749B1 (de) | 2010-05-19 |
| US7691855B2 (en) | 2010-04-06 |
| CA2491635A1 (en) | 2004-01-15 |
| US20060106027A1 (en) | 2006-05-18 |
| JP2006501183A (ja) | 2006-01-12 |
| JP4478016B2 (ja) | 2010-06-09 |
| WO2004005282A1 (en) | 2004-01-15 |
| BR0312573A (pt) | 2005-04-26 |
| PT1521749E (pt) | 2010-08-18 |
| AU2003249993A1 (en) | 2004-01-23 |
| EP1521749B8 (de) | 2010-12-22 |
| CN1330643C (zh) | 2007-08-08 |
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