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AR083711A1 - Compuestos heterociclicos utiles en el tratamiento de la hepatitis c - Google Patents

Compuestos heterociclicos utiles en el tratamiento de la hepatitis c

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Publication number
AR083711A1
AR083711A1 ARP110104276A AR083711A1 AR 083711 A1 AR083711 A1 AR 083711A1 AR P110104276 A ARP110104276 A AR P110104276A AR 083711 A1 AR083711 A1 AR 083711A1
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AR
Argentina
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alkyl
arylalkyl
heterocyclyl
aryl
unsubstituted
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Gilead Sciences Inc
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=45099196&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR083711(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of AR083711A1 publication Critical patent/AR083711A1/es

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    • C07D403/14—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 three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
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    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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    • 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
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
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    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Chemical & Material Sciences (AREA)
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  • Health & Medical Sciences (AREA)
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  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Se refiere a compuestos antivirales, composiciones que contienen dichos compuestos y métodos terapéuticos que incluyen la administración de dichos compuestos, al igual que a procesos y sustancias intermedias que resultan útiles para elaborar dichos compuestos. Reivindicación 1: Un compuesto de la fórmula (1): E1a-V1a-C(=O)-P1a-W1a-P1b-C(=O)-V1b-E1b     (1) donde: W1a tiene la fórmula (2) y W1a está opcionalmente sustituido con uno o más grupos que se seleccionan de manera independiente de halo, alquilo, haloalquilo, ciano y el resto de fórmula (3) donde cada R es, de manera independiente, H, alquilo, haloalquilo, cicloalquilo, arilo, o heteroarilo; Y5 es -O-CH2- o -CH2-O-; X5 es -CH2-CH2- o -CH=CH-; E1a es E0, E1 o E2 o E1a-V1a tomados en conjunto son R9a; E1b es E0, E1 o E2 o E1b-V1b tomados en conjunto son R9b; V1a es V0 o E1a-V1a tomados en conjunto son R9a; V1b es V0 o E1b-V1b tomados en conjunto son R9b; cada E0 es, de manera independiente, -NREcREd donde cada uno de REc y REd se selecciona, de manera independiente, de hidrógeno, alqueniloxicarbonilo, alcoxialquilcarbonilo, alcoxicarbonilo, alquilo, alquilcarbonilo, alquilsulfonilo, arilo, arilalcoxicarbonilo, arilalquilo, arilalquilcarbonilo, arilcarbonilo, ariloxicarbonilo, arilsulfonilo, cicloalquilo, cicloalquilsulfonilo, formilo, haloalcoxicarbonilo, heterociclilo, heterociclilalcoxicarbonilo, heterociclilalquilo, heterociclilalquilcarbonilo, heterociclilcarbonilo, heterocicliloxicarbonilo, hidroxialquilcarbonilo, (NReRf)alquilo, (NReRf)alquilcarbonilo, (NReRf)carbonilo, (NReRf)sulfonilo-, -C(NCN)OR’ y -C(NCN)NRXRY, donde R’ se selecciona de alquilo y fenilo insustituido, y donde la parte alquilo del arilalquilo, el arilalquilcarbonilo, el heterociclilalquilo y el heterociclilalquilcarbonilo también están opcionalmente sustituidos con un grupo -NReRf; y donde el arilo, la parte arilo del arilalcoxicarbonilo, el arilalquilo, el arilalquilcarbonilo, el arilcarbonilo, el ariloxicarbonilo y el arilsulfonilo, el heterociclilo, y la parte heterociclilo del heterociclilalcoxicarbonilo, el heterociclilalquilo, el heterociclilalquilcarbonilo, el heterociclilcarbonilo y el heterocicliloxicarbonilo también están opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados, de manera independiente, de alcoxi, alquilo, ciano, halo, haloalcoxi, haloalquilo y nitro; cada E1 se selecciona, de manera independiente, de hidrógeno, hidroxi, alquilo, haloalquilo, -NH-haloalquilo, arilo y heterociclilo; cada E2 es, de manera independiente, NHREf donde REf es cicloalquilcarbonilo o cicloalquiloxicarbonilo; cada V0 es, de manera independiente, alquilo, arilalquilo, alquenilo, CO, (cicloalquil)alquilo, cicloalquilo, alcoxialquilo, alcoxialquilcarbonilalquilo, alcoxicarbonilalquilo, alquilsulfanilalquilo, arilalcoxialquilcarbonilalquilo, carboxialquilo, heterociclilalquilo, heterociclilcarbonilalquilo, hidroxialquilo, NRVO1RVO1CO-alquilo, donde cada RVO1 se selecciona, de manera independiente, de hidrógeno y alquilo; y donde en el arilalquilo el alquilo puede estar sustituido con un máximo de tres grupos alquilo, y la parte alquilo del arilalquilo está también opcionalmente sustituida con uno o dos grupos adicionales que se seleccionan, de manera independiente, de alcoxi, alquilcarboniloxi, halo, haloalcoxi, haloalquilo, heterociclilo, hidroxi; y la parte arilo puede estar sustituida con 1, 2, 3, 4 ó 5 sustituyentes que se seleccionan, de manera independiente, de alcoxi, alcoxialquilo, alcoxicarbonilo, alquilo, alquilcarbonilo, un segundo grupo arilo, arilalcoxi, arilalquilo, arilcarbonilo, ciano, halo, haloalcoxi, haloalquilo, heterociclilo, heterociclilalquilo, heterociclilcarbonilo, hidroxi, hidroxialquilo, nitro, -NRXRY, (NRXRY)alquilo-, oxo y -P(O)(ORVO2)2, donde cada RVO2 se selecciona, de manera independiente, de hidrógeno y alquilo; y donde la parte alquilo del arilalquilo y el heterociclilalquilo están no sustituidos, y donde el segundo grupo arilo, la parte arilo del arilalquilo, la parte arilo del arilcarbonilo, el heterociclilo, y la parte heterociclilo del heterociclilalquilo y el heterociclilcarbonilo también están opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados, de manera independiente, de alcoxi, alquilo, ciano, halo, haloalcoxi, haloalquilo y nitro; y el heterociclilo puede estar sustituido con 1, 2, 3, 4 ó 5 sustituyentes que se seleccionan, de manera independiente, de alcoxi, alcoxialquilo, alcoxicarbonilo, alquilo, alquilcarbonilo, arilo, arilalquilo, arilcarbonilo, ciano, halo, haloalcoxi, haloalquilo, un segundo grupo heterociclilo, heterociclilalquilo, heterociclilcarbonilo, hidroxi, hidroxialquilo, nitro, -NRXRY, (NRXRY)alquilo- y oxo, donde la parte alquilo del arilalquilo y el heterociclilalquilo están no sustituidos y donde el arilo, la parte arilo del arilalquilo; la parte arilo del arilcarbonilo, el segundo grupo heterociclilo y la parte heterociclilo del heterociclilalquilo y el heterociclilcarbonilo también están opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados, de manera independiente, de alcoxi, alquilo, ciano, halo, haloalcoxi, haloalquilo y nitro; P1a y P1b son, cada uno de manera independiente, seleccionados del grupo de fórmulas (4); cada R9a se selecciona, de manera independiente, de alcoxi, alcoxialquilo, alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilalquilo, arilo, arilalquenilo, arilalcoxi, arilalquilo, ariloxialquilo, cicloalquilo, (cicloalquil)alquenilo, (cicloalquil)alquilo, cicloalquiloxialquilo, haloalquilo, heterociclilo, heterociclilalquenilo, heterociclilalcoxi, heterociclilalquilo, heterocicliloxialquilo, hidroxialquilo, -NRcRd, (NRcRd)alquenilo, (NRcRd)alquilo, y (NRcRd)carbonilo; Rc y Rd son seleccionados, de manera independiente, de hidrógeno, alqueniloxicarbonilo, alcoxialquilcarbonilo, alcoxicarbonilo, alquilo, alquilcarbonilo, alquilsulfonilo, arilo, arilalcoxicarbonilo, arilalquilo, arilalquilcarbonilo, arilcarbonilo, ariloxicarbonilo, arilsulfonilo, cicloalquilo, cicloalquilsulfonilo, formilo, haloalcoxicarbonilo, heterociclilo, heterociclilalcoxicarbonilo, heterociclilalquilo, heterociclilalquilcarbonilo, heterociclilcarbonilo, heterocicliloxicarbonilo, hidroxialquilcarbonilo, (NReRf)alquilo-, (NReRf)alquilcarbonilo-, (NReRf)carbonilo-, (NReRf)sulfonilo-, -C(NCN)OR’ y -C(NCN)NRXRY, donde R’ se selecciona de alquilo y fenilo insustituido, y donde la parte alquilo del arilalquilo, el arilalquilcarbonilo, el heterociclilalquilo, y el heterociclilalquilcarbonilo también están opcionalmente sustituidos con un grupo -NReRf; y donde el arilo, la parte arilo del arilalcoxicarbonilo, el arilalquilo, el arilalquilcarbonilo, el arilcarbonilo, el ariloxicarbonilo y el arilsulfonilo, el heterociclilo, y la parte heterociclilo del heterociclilalcoxicarbonilo, el heterociclilalquilo, el heterociclilalquilcarbonilo, el heterociclilcarbonilo, y el heterocicliloxicarbonilo también están opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados, de manera independiente, de alcoxi, alquilo, ciano, halo, haloalcoxi, haloalquilo y nitro; Re y Rf son seleccionados, de manera independiente, de hidrógeno, alquilo, arilo no sustituido, arilalquilo no sustituido, cicloalquilo no sustituido, (cicloalquil)alquilo no sustituido, heterociclilo no sustituido, heterociclilalquilo no sustituido, (NRXRY)alquilo-, y (NRXRY)carbonilo-; RX y RY son seleccionados, de manera independiente, de hidrógeno, alcoxicarbonilo, alquilo, alquilcarbonilo, arilo no sustituido, arilalcoxicarbonilo no sustituido, arilalquilo no sustituido, cicloalquilo no sustituido, heterociclilo no sustituido, y (NRX’RY’)carbonilo-, donde RX’ y RY’ son seleccionados, de manera independiente, de hidrógeno y alquilo; cada R9b se selecciona, de manera independiente, de alcoxi, alcoxialquilo, alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilalquilo, arilo, arilalquenilo, arilalcoxi, arilalquilo, ariloxialquilo, cicloalquilo, (cicloalquil)alquenilo, (cicloalquil)alquilo, cicloalquiloxialquilo, haloalquilo, heterociclilo, heterociclilalquenilo, heterociclilalcoxi, heterociclilalquilo, heterocicliloxialquilo, hidroxialquilo, -NRcRd, (NRcRd)alquenilo, (NRcRd)alquilo, y (NRcRd)carbonilo; Rc y Rd son seleccionados, de manera independiente, de hidrógeno, alqueniloxicarbonilo, alcoxialquilcarbonilo, alcoxicarbonilo, alquilo, alquilcarbonilo, alquilsulfonilo, arilo, arilalcoxicarbonilo, arilalquilo, arilalquilcarbonilo, arilcarbonilo, ariloxicarbonilo, arilsulfonilo, cicloalquilo, cicloalquilsulfonilo, formilo, haloalcoxicarbonilo, heterociclilo, heterociclilalcoxicarbonilo, heterociclilalquilo, heterociclilalquilcarbonilo, heterociclilcarbonilo, heterocicliloxicarbonilo, hidroxialquilcarbonilo, (NReRf)alquilo-, (NReRf)alquilcarbonilo-, (NReRf)carbonilo-, (NReRf)sulfonilo-, -C(NCN)OR’ y -C(NCN)NRXRY, donde R’ se selecciona de alquilo y fenilo insustituido, y donde la parte alquilo del arilalquilo, el arilalquilcarbonilo, el heterociclilalquilo, y el heterociclilalquilcarbonilo también están opcionalmente sustituidos con un grupo -NReRf; y donde el arilo, la parte arilo del arilalcoxicarbonilo, el arilalquilo, el arilalquilcarbonilo, el arilcarbonilo, el ariloxicarbonilo y el arilsulfonilo, el heterociclilo, y la parte heterociclilo del heterociclilalcoxicarbonilo, el heterociclilalquilo, el heterociclilalquilcarbonilo, el heterociclilcarbonilo, y el heterocicliloxicarbonilo también están opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados, de manera independiente, de alcoxi, alquilo, ciano, halo, haloalcoxi, haloalquilo y nitro; Re y Rf son seleccionados, de manera independiente, de hidrógeno, alquilo, arilo no sustituido, arilalquilo no sustituido, cicloalquilo no sustituido, (cicloalquil)alquilo no sustituido, heterociclilo no sustituido, heterociclilalquilo no sustituido, (NRXRY)alquilo, y (NRXRY)carboni
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UY33735A (es) 2012-06-29
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CA3095528A1 (en) 2012-05-24
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CA3102625A1 (en) 2012-05-24
SI2640719T1 (sl) 2017-07-31
TW201808960A (zh) 2018-03-16
US20140018313A1 (en) 2014-01-16
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IL226346A (en) 2017-12-31
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ES2634095T3 (es) 2017-09-26
WO2012068234A2 (en) 2012-05-24
EP2640719B1 (en) 2017-05-10
AU2017202461A1 (en) 2017-05-04
SG190785A1 (en) 2013-07-31
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KR20180026563A (ko) 2018-03-12
AU2019201939C1 (en) 2021-05-27
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CA3095528C (en) 2023-07-18
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JP2013542996A (ja) 2013-11-28

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