MX2022010040A - Compuestos moduladores de gcn2. - Google Patents
Compuestos moduladores de gcn2.Info
- Publication number
- MX2022010040A MX2022010040A MX2022010040A MX2022010040A MX2022010040A MX 2022010040 A MX2022010040 A MX 2022010040A MX 2022010040 A MX2022010040 A MX 2022010040A MX 2022010040 A MX2022010040 A MX 2022010040A MX 2022010040 A MX2022010040 A MX 2022010040A
- Authority
- MX
- Mexico
- Prior art keywords
- gcn2
- modulating compounds
- formula
- compounds
- modulating
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/14—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- 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
-
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Photoreceptors In Electrophotography (AREA)
- Secondary Cells (AREA)
- Liquid Crystal Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Las descripciones del presente documento se refieren a nuevos compuestos de la Fórmula (1): (ver Fórmula) (1); o una de sus sales, en donde X, Y, R1, R2, R3, R4 y R5 se definen aquí, y a su uso para tratar, prevenir, mejorar, controlar o reducir el riesgo de trastornos asociados con el Control General No depresible 2 (GCN2).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB2002144.0A GB202002144D0 (en) | 2020-02-17 | 2020-02-17 | Pharmaceutical compounds |
| GBGB2007163.5A GB202007163D0 (en) | 2020-05-14 | 2020-05-14 | Pharmaceutical compounds |
| PCT/EP2021/053928 WO2021165346A1 (en) | 2020-02-17 | 2021-02-17 | Gcn2 modulator compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2022010040A true MX2022010040A (es) | 2022-09-05 |
Family
ID=74672306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2022010040A MX2022010040A (es) | 2020-02-17 | 2021-02-17 | Compuestos moduladores de gcn2. |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20230143059A1 (es) |
| EP (1) | EP4107146A1 (es) |
| JP (1) | JP2023514328A (es) |
| KR (1) | KR20220143717A (es) |
| CN (1) | CN115768750B (es) |
| AU (1) | AU2021222818A1 (es) |
| BR (1) | BR112022016072A2 (es) |
| CA (1) | CA3170652A1 (es) |
| IL (1) | IL295487A (es) |
| MX (1) | MX2022010040A (es) |
| WO (1) | WO2021165346A1 (es) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB202008749D0 (en) | 2020-06-09 | 2020-07-22 | Ip2Ipo Innovations Ltd | Novel compounds |
| WO2021262596A1 (en) | 2020-06-22 | 2021-12-30 | Pmv Pharmaceuticals, Inc. | Methods and compounds for restoring mutant p53 function |
| AU2021381949A1 (en) | 2020-11-18 | 2023-06-15 | Deciphera Pharmaceuticals, Llc | Gcn2 and perk kinase inhibitors and methods of use thereof |
| JP2024504364A (ja) * | 2021-01-22 | 2024-01-31 | ヒベルセル, インコーポレイテッド | Gcn2をモジュレートする化合物およびその使用 |
| US20250000859A1 (en) | 2021-08-25 | 2025-01-02 | Alesta Therapeutics BV | Use of gcn2 inhibitors in treating cancer |
| JP2024544632A (ja) * | 2021-12-03 | 2024-12-03 | デシフェラ・ファーマシューティカルズ,エルエルシー | Gcn2及びperkキナーゼ阻害剤としての複素環式化合物 |
| WO2023159322A1 (en) * | 2022-02-25 | 2023-08-31 | Ontario Institute For Cancer Research (Oicr) | Quinazoline derivatives as inhibitors of the gcn2 kinase, compositions and uses thereof |
| EP4504720A1 (en) * | 2022-04-08 | 2025-02-12 | Alesta Therapeutics BV | Gcn2 modulator compounds |
| CA3252213A1 (en) | 2022-05-11 | 2023-11-16 | Ip2Ipo Innovations Limited | GCN2 INHIBITOR |
| EP4491626A4 (en) * | 2022-06-08 | 2025-07-09 | Korea Res Inst Chemical Tech | PHENYLSULFONAMIDE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITION FOR THE PREVENTION OR TREATMENT OF CANCER CONTAINING THEM AS ACTIVE INGREDIENT |
| KR102843093B1 (ko) * | 2022-06-08 | 2025-08-06 | 주식회사 애스톤사이언스 | 페닐설폰아마이드 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물 |
| CN115073282A (zh) * | 2022-06-08 | 2022-09-20 | 都创(重庆)医药科技有限公司 | 一种基于微通道连续流技术快速制备3-溴-2,4-二氟苯甲酸的方法 |
| WO2025043350A1 (en) * | 2023-08-30 | 2025-03-06 | Ontario Institute For Cancer Research (Oicr) | Triazolopyridopyrimidine and dihydroimidazopyridopyrimidine derivatives as inhibitors of the gcn2 kinase, compositions and uses thereof |
| WO2025043349A1 (en) * | 2023-08-30 | 2025-03-06 | Ontario Institute For Cancer Research (Oicr) | Pyrimidopyridone and pteridone derivatives as inhibitors of the gcn2 kinase, compositions and uses thereof |
| WO2025076441A1 (en) * | 2023-10-06 | 2025-04-10 | Alesta Therapeutics BV | Compounds of gcn2 modulators |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8846656B2 (en) * | 2011-07-22 | 2014-09-30 | Novartis Ag | Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators |
| BR112014029404A2 (pt) * | 2012-05-31 | 2017-06-27 | Hoffmann La Roche | compostos , composição farmacêutica, utilização de um composto, método para o tratamento ou profilaxia do cancêr e invenção |
| JP6374384B2 (ja) * | 2012-08-07 | 2018-08-15 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | プロテインキナーゼ阻害剤としてのピリドピリミジン誘導体 |
| RU2753520C2 (ru) * | 2016-06-21 | 2021-08-17 | НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. | Производные n-(замещенный фенил)-сульфонамида в качестве ингибиторов киназы |
| MA45940B1 (fr) * | 2016-08-10 | 2024-12-31 | Takeda Pharmaceutical Company Limited | Composé hétérocyclique |
| EP3630748B1 (en) * | 2017-06-01 | 2023-04-19 | Cornell University | Ire1 small molecule inhibitors |
| WO2020210828A1 (en) * | 2019-04-12 | 2020-10-15 | Hibercell, Inc. | (aza)indazolyl-aryl sulfonamide and related compounds and their use in treating medical conditions |
-
2021
- 2021-02-17 EP EP21706886.5A patent/EP4107146A1/en active Pending
- 2021-02-17 US US17/796,449 patent/US20230143059A1/en active Pending
- 2021-02-17 CA CA3170652A patent/CA3170652A1/en active Pending
- 2021-02-17 AU AU2021222818A patent/AU2021222818A1/en active Pending
- 2021-02-17 CN CN202180027907.5A patent/CN115768750B/zh active Active
- 2021-02-17 WO PCT/EP2021/053928 patent/WO2021165346A1/en not_active Ceased
- 2021-02-17 IL IL295487A patent/IL295487A/en unknown
- 2021-02-17 KR KR1020227032130A patent/KR20220143717A/ko not_active Withdrawn
- 2021-02-17 MX MX2022010040A patent/MX2022010040A/es unknown
- 2021-02-17 JP JP2022549485A patent/JP2023514328A/ja active Pending
- 2021-02-17 BR BR112022016072A patent/BR112022016072A2/pt not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN115768750A (zh) | 2023-03-07 |
| IL295487A (en) | 2022-10-01 |
| JP2023514328A (ja) | 2023-04-05 |
| KR20220143717A (ko) | 2022-10-25 |
| WO2021165346A1 (en) | 2021-08-26 |
| BR112022016072A2 (pt) | 2022-10-04 |
| EP4107146A1 (en) | 2022-12-28 |
| CN115768750B (zh) | 2025-09-23 |
| CA3170652A1 (en) | 2021-08-26 |
| US20230143059A1 (en) | 2023-05-11 |
| AU2021222818A1 (en) | 2022-09-01 |
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