WO2007146230A3 - Inhibiteurs de transcriptase inverse non nucléosidiques - Google Patents

Inhibiteurs de transcriptase inverse non nucléosidiques Download PDF

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Publication number
WO2007146230A3
WO2007146230A3 PCT/US2007/013689 US2007013689W WO2007146230A3 WO 2007146230 A3 WO2007146230 A3 WO 2007146230A3 US 2007013689 W US2007013689 W US 2007013689W WO 2007146230 A3 WO2007146230 A3 WO 2007146230A3
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WO
WIPO (PCT)
Prior art keywords
reverse transcriptase
transcriptase inhibitors
compounds
nucleoside reverse
prophylaxis
Prior art date
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PCT/US2007/013689
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English (en)
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WO2007146230A2 (fr
Inventor
Dai-Shi Su
Neville J Anthony
John J Lim
Elizabeth Tinney
Theresa M Williams
Original Assignee
Merck & Co Inc
Dai-Shi Su
Neville J Anthony
John J Lim
Elizabeth Tinney
Theresa M Williams
Priority date (The priority date 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 date listed.)
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Publication date
Application filed by Merck & Co Inc, Dai-Shi Su, Neville J Anthony, John J Lim, Elizabeth Tinney, Theresa M Williams filed Critical Merck & Co Inc
Publication of WO2007146230A2 publication Critical patent/WO2007146230A2/fr
Publication of WO2007146230A3 publication Critical patent/WO2007146230A3/fr

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    • 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
    • C07D215/04—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C07D215/08—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • 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
    • C07D215/18—Halogen atoms or nitro radicals
    • 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
    • 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
    • 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
    • C07D215/40—Nitrogen atoms attached in position 8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/16—Benzazepines; Hydrogenated benzazepines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines 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 carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
    • 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
    • C07D401/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D401/08—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 carbon chain containing alicyclic rings
    • 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
    • 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
    • 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
    • C07D413/12—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 chain containing hetero atoms as chain links
    • 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
    • C07D417/08—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 alicyclic 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
    • 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
    • C07D417/14—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 three or more hetero rings
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des inhibiteurs de transcriptase inverse de VIH, qui sont les composés de Formule I : (I) dans laquelle X, U, V, W, R1, R2, R3, R4, n, p et q sont tels que définis dans l'invention. Les composés de Formule I et leurs sels de qualité pharmaceutique peuvent être employés dans l'inhibition de la transcriptase inverse du VIH, dans le traitement prophylactique et thérapeutique d'une infection par le VIH et dans le traitement prophylactique, le retard de l'apparition ou le traitement thérapeutique du SIDA. Les composés et leurs sels peuvent être employés en tant qu'ingrédients dans des compositions pharmaceutiques, éventuellement combinés à d'autres agents antiviraux, immunomodulateurs, antibiotiques ou vaccins.
PCT/US2007/013689 2006-06-14 2007-06-07 Inhibiteurs de transcriptase inverse non nucléosidiques WO2007146230A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US81349006P 2006-06-14 2006-06-14
US60/813,490 2006-06-14

Publications (2)

Publication Number Publication Date
WO2007146230A2 WO2007146230A2 (fr) 2007-12-21
WO2007146230A3 true WO2007146230A3 (fr) 2008-12-11

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ES2927660T3 (es) 2008-06-16 2022-11-10 Univ Tennessee Res Found Compuestos para el tratamiento del cáncer
US9029408B2 (en) 2008-06-16 2015-05-12 Gtx, Inc. Compounds for treatment of cancer
US9447049B2 (en) 2010-03-01 2016-09-20 University Of Tennessee Research Foundation Compounds for treatment of cancer
WO2010110414A1 (fr) * 2009-03-27 2010-09-30 田辺三菱製薬株式会社 Compose amide d'acide indazolepropionique
KR20120130777A (ko) 2010-03-01 2012-12-03 유니버시티 오브 테네시 리서치 파운데이션 암 치료용 화합물
BR112012024380A2 (pt) 2010-03-25 2015-09-15 Glaxosmithkline Llc compostos químicos
AR088729A1 (es) 2011-03-29 2014-07-02 Actelion Pharmaceuticals Ltd Derivados de 3-ureidoisoquinolin-8-ilo y una composicion farmaceutica
KR20150005936A (ko) 2012-04-25 2015-01-15 다케다 야쿠힌 고교 가부시키가이샤 질소화 헤테로시클릭 화합물
EP2873669A4 (fr) 2012-07-13 2015-11-25 Takeda Pharmaceutical Composé hétérocyclique
TW201444798A (zh) 2013-02-28 2014-12-01 必治妥美雅史谷比公司 作爲強效ｒｏｃｋ１及ｒｏｃｋ２抑制劑之苯基吡唑衍生物
EP2961746B1 (fr) 2013-02-28 2018-01-03 Bristol-Myers Squibb Company Dérivés de phénylpyrazole en tant que puissants inhibiteurs de rock1 et rock2
US9834520B2 (en) 2013-03-14 2017-12-05 Takeda Pharmaceutical Company Limited Heterocyclic compound
JP6427491B2 (ja) 2013-07-03 2018-11-21 武田薬品工業株式会社 複素環化合物
ES2950424T3 (es) 2013-07-03 2023-10-09 Takeda Pharmaceuticals Co Compuesto de amida
SG11201602183QA (en) 2013-10-25 2016-05-30 Novartis Ag Ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors
WO2015074064A2 (fr) 2013-11-18 2015-05-21 Bair Kenneth W Compositions de tétrahydroquinoline utilisées comme inhibiteurs de protéines à bromodomaine et domaine extraterminal (bet)
EP3071205B1 (fr) 2013-11-18 2020-02-05 Forma Therapeutics, Inc. Compositions de benzopipérazine en tant qu'inhibiteurs de bromodomaines bet
EP3200786B1 (fr) 2014-10-03 2019-08-28 Novartis AG Utilisation de dérivés pyridyle bicycliques à anneaux fusionnés en tant qu'inhibiteurs de fgfr4
US9802917B2 (en) 2015-03-25 2017-10-31 Novartis Ag Particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4294832A (en) * 1979-04-28 1981-10-13 Tanabe Seiyaku Co., Ltd. Tetrahydroisoquinoline compounds and a pharmaceutical composition thereof
US5527819A (en) * 1991-09-06 1996-06-18 Merck & Co., Inc. Inhibitors of HIV reverse transcriptase
US5840727A (en) * 1989-05-19 1998-11-24 Hoechst Marion Roussel Inc (4-heteroaryl)-1- (2,3-dihydro-1H-isoindol-2-yl) alkyl! piperazines and related compounds and their therapeutic utility
US6063806A (en) * 1995-10-05 2000-05-16 Kyoto Pharmaceutical Industries, Ltd. Indolyl or indolinyl derivatives and medicinal use thereof as ACAT or lipid peroxidation inhibitors
US6329389B1 (en) * 1998-04-08 2001-12-11 Takeda Chemical Industries, Ltd. Amine compounds, their production and use
US20030125344A1 (en) * 2001-03-23 2003-07-03 Bayer Corporation Rho-kinase inhibitors
US20040082571A1 (en) * 2002-06-12 2004-04-29 Chemocentryx, Inc. Substituted piperazines
WO2007021629A2 (fr) * 2005-08-11 2007-02-22 Merck & Co., Inc. Inhibiteurs non nucleosidiques de la transcriptase inverse

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4294832A (en) * 1979-04-28 1981-10-13 Tanabe Seiyaku Co., Ltd. Tetrahydroisoquinoline compounds and a pharmaceutical composition thereof
US5840727A (en) * 1989-05-19 1998-11-24 Hoechst Marion Roussel Inc (4-heteroaryl)-1- (2,3-dihydro-1H-isoindol-2-yl) alkyl! piperazines and related compounds and their therapeutic utility
US5527819A (en) * 1991-09-06 1996-06-18 Merck & Co., Inc. Inhibitors of HIV reverse transcriptase
US6063806A (en) * 1995-10-05 2000-05-16 Kyoto Pharmaceutical Industries, Ltd. Indolyl or indolinyl derivatives and medicinal use thereof as ACAT or lipid peroxidation inhibitors
US6329389B1 (en) * 1998-04-08 2001-12-11 Takeda Chemical Industries, Ltd. Amine compounds, their production and use
US20030125344A1 (en) * 2001-03-23 2003-07-03 Bayer Corporation Rho-kinase inhibitors
US20040082571A1 (en) * 2002-06-12 2004-04-29 Chemocentryx, Inc. Substituted piperazines
WO2007021629A2 (fr) * 2005-08-11 2007-02-22 Merck & Co., Inc. Inhibiteurs non nucleosidiques de la transcriptase inverse

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