ES2610360T3 - Compuestos de imidazotriazinona - Google Patents
Compuestos de imidazotriazinona Download PDFInfo
- Publication number
- ES2610360T3 ES2610360T3 ES11761793.6T ES11761793T ES2610360T3 ES 2610360 T3 ES2610360 T3 ES 2610360T3 ES 11761793 T ES11761793 T ES 11761793T ES 2610360 T3 ES2610360 T3 ES 2610360T3
- Authority
- ES
- Spain
- Prior art keywords
- imidazo
- trans
- triazin
- mmol
- methylpyrrolidin
- 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.)
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- IJYHVZICHKCLMQ-UHFFFAOYSA-N imidazo[4,5-d]triazin-4-one Chemical class O=C1N=NN=C2N=CN=C12 IJYHVZICHKCLMQ-UHFFFAOYSA-N 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 150000001875 compounds Chemical class 0.000 claims description 147
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 135
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- 101100407341 Drosophila melanogaster Pde9 gene Proteins 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 48
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 claims description 33
- 239000003814 drug Substances 0.000 claims description 28
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- 208000024827 Alzheimer disease Diseases 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 24
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims description 23
- 206010012289 Dementia Diseases 0.000 claims description 18
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- NIHUZJPITMUICY-UHFFFAOYSA-N 1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound O=C1NC=NN2C=NC=C12 NIHUZJPITMUICY-UHFFFAOYSA-N 0.000 abstract description 158
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 379
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 318
- -1 (pyrimidin-2-ylmethyl) pyrrolidin-3-yl Chemical group 0.000 description 290
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 195
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 178
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 153
- 239000000243 solution Substances 0.000 description 149
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 144
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 125
- 238000004809 thin layer chromatography Methods 0.000 description 105
- 238000005160 1H NMR spectroscopy Methods 0.000 description 103
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 95
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- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 55
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 55
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 50
- 230000002829 reductive effect Effects 0.000 description 49
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 48
- 239000012043 crude product Substances 0.000 description 48
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 47
- 239000013058 crude material Substances 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
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- 238000004296 chiral HPLC Methods 0.000 description 39
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 35
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 33
- ZHGNHOOVYPHPNJ-UHFFFAOYSA-N Amigdalin Chemical compound FC(F)(F)C(=O)OCC1OC(OCC2OC(OC(C#N)C3=CC=CC=C3)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C2OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C1OC(=O)C(F)(F)F ZHGNHOOVYPHPNJ-UHFFFAOYSA-N 0.000 description 33
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 31
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- 229910052736 halogen Inorganic materials 0.000 description 27
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- PGJLOGNVZGRMGX-UHFFFAOYSA-L iron(2+);trifluoromethanesulfonate Chemical compound [Fe+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F PGJLOGNVZGRMGX-UHFFFAOYSA-L 0.000 description 27
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38469410P | 2010-09-20 | 2010-09-20 | |
| US384694P | 2010-09-20 | ||
| PCT/US2011/052399 WO2012040230A1 (en) | 2010-09-20 | 2011-09-20 | Imidazotriazinone compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2610360T3 true ES2610360T3 (es) | 2017-04-27 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11761793.6T Active ES2610360T3 (es) | 2010-09-20 | 2011-09-20 | Compuestos de imidazotriazinona |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US20120157458A1 (https=) |
| EP (2) | EP2619208B1 (https=) |
| JP (2) | JP5855109B2 (https=) |
| CN (1) | CN103313988B (https=) |
| AR (1) | AR083058A1 (https=) |
| AU (2) | AU2011305568B2 (https=) |
| BR (1) | BR112013008140A8 (https=) |
| CA (1) | CA2811714C (https=) |
| DK (1) | DK2619208T3 (https=) |
| ES (1) | ES2610360T3 (https=) |
| MX (1) | MX2013003093A (https=) |
| PL (1) | PL2619208T3 (https=) |
| RU (1) | RU2603140C2 (https=) |
| TW (1) | TWI541244B (https=) |
| UY (1) | UY33616A (https=) |
| WO (1) | WO2012040230A1 (https=) |
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| EP2619208B1 (en) | 2010-09-20 | 2016-11-09 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| BR112015007731B1 (pt) * | 2011-10-10 | 2022-05-31 | H. Lundbeck A/S | Composto, composição farmacêutica que o compreende e uso do mesmo |
| BR112014018199A8 (pt) * | 2012-01-26 | 2021-03-02 | H Lundbeck As | inibidores da pde9 com cadeia principal imidazo triazinona, composição farmacêutica que os compreende, uso dos referidos inibidores e processo para sua preparação |
| HK1206726A1 (en) | 2012-03-19 | 2016-01-15 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| CN102786525B (zh) | 2012-08-08 | 2014-12-17 | 中山大学 | N-取代吡唑并[3,4-d]嘧啶酮类化合物、其制备方法及其应用 |
| WO2014024125A1 (en) | 2012-08-08 | 2014-02-13 | Celon Pharma S.A. | Pyrazolo[4,3-d]pyrimidin-7(6h)-one derivatives as pde9 inhibitors |
| JP2016503395A (ja) | 2012-10-31 | 2016-02-04 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 病害生物防除剤としての複素環化合物 |
| TW201629064A (zh) | 2014-10-10 | 2016-08-16 | Ｈ 朗德貝克公司 | 作爲ｐｄｅ１抑制劑之三唑並吡酮 |
| TW201639851A (zh) * | 2015-03-16 | 2016-11-16 | 大日本住友製藥股份有限公司 | 雙環咪唑衍生物 |
| TW201643167A (zh) * | 2015-04-22 | 2016-12-16 | Ｈ 朗德貝克公司 | 作爲ｐｄｅ１抑制劑之咪唑並三酮 |
| JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| PT3865484T (pt) | 2015-07-07 | 2024-01-30 | H Lundbeck As | Inibidor da pde9 com esqueleto de imidazo pirazinona para tratamento de doenças periféricas |
| WO2017070293A1 (en) * | 2015-10-20 | 2017-04-27 | Ironwood Pharmaceuticals, Inc. | Phosphodiesterase 9 inhibitor and levodopa therapy |
| CN105669680B (zh) * | 2016-03-24 | 2018-02-23 | 南京药捷安康生物科技有限公司 | 吡咯并[2,1‑f][1,2,4]三嗪‑4(1H)‑酮衍生物类PDE9A抑制剂 |
| TWI729109B (zh) | 2016-04-12 | 2021-06-01 | 丹麥商Ｈ 朗德貝克公司 | 作爲PDE1抑制劑的1,5-二氫-4H-吡唑并[3,4-d]嘧啶-4-酮和1,5-二氫-4H-吡唑并[4,3-c]吡啶-4-酮 |
| MX2018016127A (es) | 2016-07-06 | 2019-05-30 | Imara Inc | Inhibidores de pde9 para el tratamiento de enfermedades perifericas. |
| WO2018073251A1 (en) | 2016-10-18 | 2018-04-26 | H. Lundbeck A/S | Imidazopyrazinones, pyrazolopyrimidinones and pyrazolopyridinones as pde1 inhibitors |
| AU2017350473A1 (en) | 2016-10-28 | 2019-04-18 | H. Lundbeck A/S | Combination treatments comprising imidazopyrazinones for the treatment of psychiatric and/or cognitive disorders |
| WO2018078042A1 (en) | 2016-10-28 | 2018-05-03 | H. Lundbeck A/S | Combination treatments comprising administration of imidazopyrazinones |
| CN115746003B (zh) * | 2017-05-26 | 2024-08-09 | 卡都瑞恩医药公司 | 制备和使用pde9抑制剂的方法 |
| CA3100988A1 (en) | 2018-05-25 | 2019-11-28 | Imara Inc. | Monohydrate and crystalline forms of 6-[(3s,4s)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-tetrahydropyran-4-yl-7h-imidazo[1,5-a]pyrazin-8-one |
| CA3110680A1 (en) | 2018-08-31 | 2020-03-05 | Imara Inc. | Pde9 inhibitors for treating sickle cell disease |
| WO2020102374A1 (en) * | 2018-11-14 | 2020-05-22 | The Board Of Trustees Of The Leland Stanford Junior University | Targeting of makap-pde4d3 complexes in neurodegenerative disease |
| KR102712818B1 (ko) * | 2018-12-06 | 2024-09-30 | 한국화학연구원 | Pde9a 저해 활성을 가지는 화합물 및 이들의 의약 용도 |
| CA3155013A1 (en) * | 2019-10-21 | 2021-04-29 | Ki Ho Lee | Use of imidazopyrimidine or imidazotriazine compound for prevention, alleviation, or treatment of developmental disability |
| CN112724079A (zh) * | 2021-02-04 | 2021-04-30 | 康化（上海）新药研发有限公司 | 一种6-甲氧基吡啶甲酸甲酯的合成方法 |
| GB2632307A (en) * | 2023-08-02 | 2025-02-05 | Duke Street Bio Ltd | PARP1 inhibitor compounds |
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| PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
| DE19750085A1 (de) * | 1997-11-12 | 1999-05-20 | Bayer Ag | 2-Phenyl-substituierte Imidazotriazinone |
| CA2395558C (en) | 1997-11-12 | 2007-07-17 | Bayer Aktiengesellschaft | Intermediates for 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors |
| GB0113343D0 (en) * | 2001-06-01 | 2001-07-25 | Bayer Ag | Novel Heterocycles 2 |
| US7087605B2 (en) | 2001-06-01 | 2006-08-08 | Bayer Aktiengesellschaft | 5-Ethyl-imidazotriazinones |
| JP2005508978A (ja) * | 2001-11-02 | 2005-04-07 | ファイザー・プロダクツ・インク | Ｐｄｅ９阻害薬によるインスリン抵抗性症候群及び２型糖尿病の治療 |
| DE10229778A1 (de) * | 2002-07-03 | 2004-01-29 | Bayer Ag | Neue Verwendung von Imidazotriazinonen |
| JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
| US20040220186A1 (en) | 2003-04-30 | 2004-11-04 | Pfizer Inc. | PDE9 inhibitors for treating type 2 diabetes,metabolic syndrome, and cardiovascular disease |
| WO2006127368A2 (en) | 2005-05-20 | 2006-11-30 | Lexicon Genetics Incorporated | Methods for synthesizing imidazotriazinones |
| JP2008543968A (ja) | 2005-06-28 | 2008-12-04 | オーキッド リサーチ ラボラトリーズ リミテッド | 新規なピラゾロピリミジノン誘導体 |
| RS52166B (sr) * | 2007-05-11 | 2012-08-31 | Pfizer Inc. | Amino-heterociklična jedinjenja |
| BRPI0914772A2 (pt) | 2008-06-25 | 2015-10-20 | Envivo Pharmaceuticals Inc | compostos heterocíclicos 1,2-dissubstituídos |
| EP2619208B1 (en) | 2010-09-20 | 2016-11-09 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| BR112014018199A8 (pt) | 2012-01-26 | 2021-03-02 | H Lundbeck As | inibidores da pde9 com cadeia principal imidazo triazinona, composição farmacêutica que os compreende, uso dos referidos inibidores e processo para sua preparação |
| HK1206726A1 (en) | 2012-03-19 | 2016-01-15 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
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- 2011-09-20 EP EP16197573.5A patent/EP3181566A1/en not_active Withdrawn
- 2011-09-20 UY UY0001033616A patent/UY33616A/es unknown
- 2011-09-20 BR BR112013008140A patent/BR112013008140A8/pt not_active IP Right Cessation
- 2011-09-20 TW TW100133825A patent/TWI541244B/zh not_active IP Right Cessation
- 2011-09-20 AR ARP110103426A patent/AR083058A1/es unknown
- 2011-09-20 JP JP2013530234A patent/JP5855109B2/ja not_active Expired - Fee Related
- 2011-09-20 WO PCT/US2011/052399 patent/WO2012040230A1/en not_active Ceased
- 2011-09-20 CN CN201180055157.9A patent/CN103313988B/zh not_active Expired - Fee Related
-
2014
- 2014-07-17 US US14/334,073 patent/US9540380B2/en not_active Expired - Fee Related
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2015
- 2015-12-08 JP JP2015239514A patent/JP2016104747A/ja active Pending
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2016
- 2016-02-16 AU AU2016200970A patent/AU2016200970A1/en not_active Abandoned
- 2016-12-07 US US15/371,935 patent/US20170152265A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US9540380B2 (en) | 2017-01-10 |
| DK2619208T3 (en) | 2017-01-30 |
| JP2016104747A (ja) | 2016-06-09 |
| BR112013008140A2 (pt) | 2017-12-05 |
| US20170152265A1 (en) | 2017-06-01 |
| BR112013008140A8 (pt) | 2018-04-03 |
| RU2013118362A (ru) | 2014-10-27 |
| PL2619208T3 (pl) | 2017-03-31 |
| EP3181566A1 (en) | 2017-06-21 |
| AU2016200970A1 (en) | 2016-03-03 |
| AR083058A1 (es) | 2013-01-30 |
| EP2619208A1 (en) | 2013-07-31 |
| CA2811714A1 (en) | 2012-03-29 |
| CN103313988A (zh) | 2013-09-18 |
| US20120157458A1 (en) | 2012-06-21 |
| EP2619208B1 (en) | 2016-11-09 |
| WO2012040230A1 (en) | 2012-03-29 |
| US20140330014A1 (en) | 2014-11-06 |
| MX2013003093A (es) | 2013-10-28 |
| CA2811714C (en) | 2017-11-21 |
| AU2011305568B2 (en) | 2015-12-10 |
| AU2011305568A1 (en) | 2013-04-04 |
| UY33616A (es) | 2012-04-30 |
| TWI541244B (zh) | 2016-07-11 |
| RU2603140C2 (ru) | 2016-11-20 |
| HK1187908A1 (en) | 2014-04-17 |
| JP2013540755A (ja) | 2013-11-07 |
| TW201217381A (en) | 2012-05-01 |
| CN103313988B (zh) | 2016-06-08 |
| JP5855109B2 (ja) | 2016-02-09 |
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