CN105263934B - 作为bet抑制剂的吡唑并‑吡咯烷‑4‑酮衍生物及其在治疗疾病中的用途 - Google Patents

作为bet抑制剂的吡唑并‑吡咯烷‑4‑酮衍生物及其在治疗疾病中的用途 Download PDF

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Publication number
CN105263934B
CN105263934B CN201480030590.0A CN201480030590A CN105263934B CN 105263934 B CN105263934 B CN 105263934B CN 201480030590 A CN201480030590 A CN 201480030590A CN 105263934 B CN105263934 B CN 105263934B
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methyl
cyclopropyl
pyrazoles
pyridine
chlorphenyls
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Chinese (zh)
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CN105263934A (zh
Inventor
J·布兰克
G·博尔德
S·科泰斯塔
V·瓜格纳诺
H·鲁伊格尔
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Novartis AG
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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
    • A61K31/41921,2,3-Triazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/5025Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201480030590.0A 2013-05-28 2014-05-27 作为bet抑制剂的吡唑并‑吡咯烷‑4‑酮衍生物及其在治疗疾病中的用途 Expired - Fee Related CN105263934B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP13169441.6 2013-05-28
EP13169441 2013-05-28
PCT/IB2014/061736 WO2014191906A1 (en) 2013-05-28 2014-05-27 Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease

Publications (2)

Publication Number Publication Date
CN105263934A CN105263934A (zh) 2016-01-20
CN105263934B true CN105263934B (zh) 2017-09-08

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CN201480030590.0A Expired - Fee Related CN105263934B (zh) 2013-05-28 2014-05-27 作为bet抑制剂的吡唑并‑吡咯烷‑4‑酮衍生物及其在治疗疾病中的用途

Country Status (14)

Country Link
US (1) US9624247B2 (https=)
EP (1) EP3004108B1 (https=)
JP (1) JP2016520118A (https=)
KR (1) KR20160012195A (https=)
CN (1) CN105263934B (https=)
AU (1) AU2014272695B2 (https=)
BR (1) BR112015029401A8 (https=)
CA (1) CA2912986A1 (https=)
EA (1) EA028175B1 (https=)
ES (1) ES2656471T3 (https=)
MX (1) MX2015016421A (https=)
PL (1) PL3004108T3 (https=)
PT (1) PT3004108T (https=)
WO (1) WO2014191906A1 (https=)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG11201506924YA (en) 2013-03-15 2015-09-29 Incyte Corp Tricyclic heterocycles as bet protein inhibitors
MX2015016421A (es) 2013-05-28 2016-03-03 Novartis Ag Derivados de pirazolo-pirrolidin-4-ona como inhibidores de bet y su uso en el tratamiento de enfermedades.
EP3019502B1 (en) 2013-07-08 2017-05-17 Incyte Holdings Corporation Tricyclic heterocycles as bet protein inhibitors
US9399640B2 (en) 2013-11-26 2016-07-26 Incyte Corporation Substituted pyrrolo[2,3-c]pyridines and pyrazolo[3,4-c]pyridines as BET protein inhibitors
WO2015081189A1 (en) 2013-11-26 2015-06-04 Incyte Corporation Bicyclic heterocycles as bet protein inhibitors
WO2015095492A1 (en) 2013-12-19 2015-06-25 Incyte Corporation Tricyclic heterocycles as bet protein inhibitors
PL3134403T3 (pl) 2014-04-23 2020-07-13 Incyte Corporation 1H-pirolo[2,3-c]pirydyn-7(6H)-ony i pirazolo[3,4-c]pirydyn-7(6H)-ony jako inhibitory białek BET
JP6599979B2 (ja) 2014-09-15 2019-10-30 インサイト・コーポレイション Betタンパク質阻害剤として用いるための三環式複素環化合物
GB201504694D0 (en) 2015-03-19 2015-05-06 Glaxosmithkline Ip Dev Ltd Covalent conjugates
WO2017075377A1 (en) 2015-10-29 2017-05-04 Incyte Corporation Amorphous solid form of a bet protein inhibitor
KR20180134860A (ko) 2016-02-15 2018-12-19 체엠엠 - 포르슝스첸트룸 퓨어 몰레쿨라레 메디친 게엠베하 암의 치료를 위한 taf1 억제제
CA3028689A1 (en) 2016-06-20 2017-12-28 Incyte Corporation Crystalline solid forms of a bet inhibitor
US20190262355A1 (en) 2016-11-14 2019-08-29 Cemm-Forschungszentrum Für Molekulare Medizin Gmbh Combination of a brd4 inhibitor and an antifolate for the therapy of cancer
JP7840635B2 (ja) 2017-12-20 2026-04-06 貝達薬業股▲ふん▼有限公司 ブロモドメインタンパク質阻害剤である化合物、および組成物
KR20210031852A (ko) * 2018-03-05 2021-03-23 클리니쿰 레히츠 데어 이자르 데어 테크니쉔 우니베르지테트 뮌헨 종양 세포 붕괴성 아데노바이러스와 cdk4/6 억제제의 조합물에 의한 종양의 치료
MX2022000521A (es) * 2019-07-12 2022-06-14 Scenic Immunology B V Compuestos n-sustituidos-3,4-(5-anillo fusionado)-5-fenil-pirrolid in-2-ona como inhibidores de la enzima isoqc y/o qc.
US11833155B2 (en) 2020-06-03 2023-12-05 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012151512A2 (en) * 2011-05-04 2012-11-08 Constellation Pharmaceuticals, Inc. Bromodomain inhibitors and uses thereof
WO2012174487A2 (en) * 2011-06-17 2012-12-20 Constellation Pharmaceuticals, Inc. Bromodomain inhibitors and uses thereof

Family Cites Families (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3829420A (en) 1970-07-13 1974-08-13 Sumitomo Chemical Co 3,4-dihydro-2(1h)-quinazolinones and preparation thereof
US4099002A (en) 1970-12-23 1978-07-04 Sumitomo Chemical Company, Limited Quinazolinone derivatives and a process for production thereof
JPS4822715B1 (https=) 1970-12-28 1973-07-07
JPS5427356B2 (https=) 1972-03-31 1979-09-10
US4258187A (en) 1977-06-16 1981-03-24 E. I. Du Pont De Nemours And Company Process for preparing quinazolinone oxides
US4335127A (en) 1979-01-08 1982-06-15 Janssen Pharmaceutica, N.V. Piperidinylalkyl quinazoline compounds, composition and method of use
JPS5721388A (en) 1980-07-11 1982-02-04 Nippon Nohyaku Co Ltd Condensed pyrazole derivative
DE3420799A1 (de) 1984-06-04 1985-12-05 Bayer Ag, 5090 Leverkusen Chromogene 4,4-diaryl-dihydrochinazolone, ihre herstellung und verwendung
AU2436792A (en) 1991-08-16 1993-03-16 Merck & Co., Inc. Quinazoline derivatives as inhibitors of hiv reverse transcriptase
US5508300A (en) 1994-01-14 1996-04-16 Pfizer Inc. Dihydro pyrazolopyrroles, compositions and use
EP0958305B1 (en) 1996-07-05 2008-06-04 Cancer Research Technology Limited Inhibitions of the interaction between p53 and mdm2
HRP980143A2 (en) 1997-04-09 1999-02-28 Soo Sung Ko 4,4-disubstituted-3,4-dihydro-2 (1h)-quinazolinones useful as hiv reverse transcriptase inhibitors
WO2000066560A1 (en) 1999-05-04 2000-11-09 American Home Products Corporation Quinazolinone and benzoxazine derivatives as progesterone receptor modulators
JP2001302515A (ja) 2000-04-18 2001-10-31 Sumitomo Pharmaceut Co Ltd ポリ(adp−リボース)ポリメラーゼ阻害剤
US6479499B1 (en) 2000-06-28 2002-11-12 National Science Council 2-phenyl-4-quinazolinone compounds, 2-phenyl-4-alkoxy-quinazoline compounds and their pharmaceutical compositions
DK1320531T3 (da) 2000-08-10 2011-01-03 Pfizer Italia Srl Bicyclo-pyrazoler, der er aktive som kinase inhibitorer, fremgangsmåde til fremstilling deraf og farmaceutiske sammensætninger, der indeholder disse
PL370823A1 (en) 2001-12-18 2005-05-30 F.Hoffmann-La Roche Ag Cis-2,4,5- triphenyl-imidazolines and their use in the treatment of tumors
CA2473740A1 (en) 2002-01-18 2003-07-31 David Solow-Cordero Methods of treating conditions associated with an edg receptor
US20060189511A1 (en) 2002-05-13 2006-08-24 Koblish Holly K Method for cytoprotection through mdm2 and hdm2 inhibition
US7119111B2 (en) 2002-05-29 2006-10-10 Amgen, Inc. 2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use
AU2003253165A1 (en) 2002-08-13 2004-02-25 Warner-Lambert Company Llc Pyrimidine fused bicyclic metalloproteinase inhibitors
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
US20040214856A1 (en) 2003-04-23 2004-10-28 Pfizer Inc Cannabinoid receptor ligands and uses thereof
US7145012B2 (en) 2003-04-23 2006-12-05 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US20040213264A1 (en) 2003-04-25 2004-10-28 Nortel Networks Limited Service class and destination dominance traffic management
EP1657238A4 (en) 2003-08-22 2008-12-03 Takeda Pharmaceutical CONDENSATE PYRIMIDINE DERIVATIVE AND ITS USE
WO2005027882A1 (en) 2003-09-22 2005-03-31 Bionetworks Gmbh Prevention and treatment of inflammation-induced and/or immune-mediated bone loss
KR20060127413A (ko) 2003-11-25 2006-12-12 카이론 코포레이션 항암제로서의 퀴나졸리논 화합물
JP4814228B2 (ja) 2004-05-18 2011-11-16 エフ.ホフマン−ラ ロシュ アーゲー 新規cis−イミダゾリン
EP1750706B1 (en) 2004-06-01 2016-10-05 University Of Virginia Patent Foundation Dual small molecule inhibitors of cancer and angiogenesis
GB0419481D0 (en) 2004-09-02 2004-10-06 Cancer Rec Tech Ltd Isoindolin-1-one derivatives
US20060069085A1 (en) 2004-09-28 2006-03-30 Rulin Zhao Preparation of 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones
WO2006074262A1 (en) 2005-01-05 2006-07-13 Rigel Pharmaceuticals, Inc. Ubiquitin ligase inhibitors
US20080153791A1 (en) 2005-03-18 2008-06-26 Onpharm Gmbh 11Beta -Hydroxysteroid Dehydrogenases
WO2006100038A1 (en) 2005-03-23 2006-09-28 Syngenta Participations Ag Triazolopyrimidine derivatives useful as fungicides
US7576082B2 (en) 2005-06-24 2009-08-18 Hoffman-La Roche Inc. Oxindole derivatives
JP5222731B2 (ja) 2005-12-12 2013-06-26 ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ キナーゼ阻害薬として活性な置換ピロロ−ピラゾール誘導体
WO2007096334A1 (en) 2006-02-24 2007-08-30 Pfizer Italia Srl Pyrrolopyrrolones active as kinase inhibitors
DE102006016426A1 (de) 2006-04-07 2007-10-11 Merck Patent Gmbh Neuartige Cyclobutyl-Verbindungen als Kinase-Inhibitoren
WO2007144384A1 (en) 2006-06-14 2007-12-21 4Sc Ag Pyrazolopyrimidones
US8222288B2 (en) 2006-08-30 2012-07-17 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 and the uses thereof
WO2008034039A2 (en) 2006-09-15 2008-03-20 Nexuspharma Inc. Novel tetrahydro-isoquinolines
WO2008045529A1 (en) 2006-10-12 2008-04-17 Serenex, Inc. Purine and pyrimidine derivatives for treatment of cancer and inflammatory diseases
TW200843739A (en) 2007-03-30 2008-11-16 Shionogi & Co Novel pyrrolinone derivative and composition containing the same
WO2008130614A2 (en) 2007-04-20 2008-10-30 University Of Pittsburg-Of The Commonwealth System Of Higher Education Selective and dual-action p53/mdm2/mdm4 antagonists
WO2009086303A2 (en) 2007-12-21 2009-07-09 University Of Rochester Method for altering the lifespan of eukaryotic organisms
UY31982A (es) 2008-07-16 2010-02-26 Boehringer Ingelheim Int Derivados de 1,2-dihidropiridin-3-carboxamidas n-sustituidas
TW201016702A (en) 2008-09-25 2010-05-01 Shionogi & Co Novel pyrrolinone derivative and pharmaceutical composition comprising the same
CN102272135A (zh) 2008-10-08 2011-12-07 百时美施贵宝公司 唑并吡咯酮黑色素浓集激素受体-1拮抗剂
JP5752601B2 (ja) 2008-12-08 2015-07-22 ブイエム ファーマ エルエルシー タンパク質受容体チロシンキナーゼ阻害薬の組成物
WO2010141738A2 (en) 2009-06-03 2010-12-09 President And Fellows Of Harvard College Compositions and method for inhibiting tumor growth
GB0919423D0 (en) * 2009-11-05 2009-12-23 Glaxosmithkline Llc Novel compounds
CU24130B1 (es) 2009-12-22 2015-09-29 Novartis Ag Isoquinolinonas y quinazolinonas sustituidas
US8440693B2 (en) 2009-12-22 2013-05-14 Novartis Ag Substituted isoquinolinones and quinazolinones
JP5844358B2 (ja) 2010-06-22 2016-01-13 グラクソスミスクライン エルエルシー ベンゾトリアゾロジアゼピン化合物を含むブロモドメイン阻害剤
US20120065210A1 (en) 2010-09-15 2012-03-15 Xin-Jie Chu Substituted hexahydropyrrolo[1,2-c]imidazolones
GB201016880D0 (en) 2010-10-07 2010-11-17 Riotech Pharmaceuticals Ltd Phosphodiesterase inhibitors
JP2014500870A (ja) 2010-11-12 2014-01-16 ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、ミシガン スピロ−オキシインドールmdm2アンタゴニスト
AR084070A1 (es) * 2010-12-02 2013-04-17 Constellation Pharmaceuticals Inc Inhibidores del bromodominio y usos de los mismos
WO2012175520A1 (en) 2011-06-20 2012-12-27 Novartis Ag Hydroxy substituted isoquinolinone derivatives
US8859586B2 (en) 2011-06-20 2014-10-14 Novartis Ag Cyclohexyl isoquinolinone compounds
WO2013027168A1 (en) 2011-08-22 2013-02-28 Pfizer Inc. Novel heterocyclic compounds as bromodomain inhibitors
WO2013033268A2 (en) 2011-08-29 2013-03-07 Coferon, Inc. Bivalent bromodomain ligands, and methods of using same
WO2013080141A1 (en) * 2011-11-29 2013-06-06 Novartis Ag Pyrazolopyrrolidine compounds
WO2013097052A1 (en) 2011-12-30 2013-07-04 Abbott Laboratories Bromodomain inhibitors
UY34591A (es) 2012-01-26 2013-09-02 Novartis Ag Compuestos de imidazopirrolidinona
US20130281396A1 (en) 2012-04-19 2013-10-24 Rvx Therapeutics Inc. Treatment of diseases by epigenetic regulation
US20130281399A1 (en) 2012-04-19 2013-10-24 Rvx Therapeutics Inc. Treatment of diseases by epigenetic regulation
US20130281397A1 (en) 2012-04-19 2013-10-24 Rvx Therapeutics Inc. Treatment of diseases by epigenetic regulation
CA2870931A1 (en) 2012-04-20 2013-10-24 Abbvie Inc. Isoindolone derivatives
EP2855483B1 (en) 2012-05-24 2017-10-25 Novartis AG Pyrrolopyrrolidinone compounds
US8975417B2 (en) * 2013-05-27 2015-03-10 Novartis Ag Pyrazolopyrrolidine derivatives and their use in the treatment of disease
MX2015016421A (es) 2013-05-28 2016-03-03 Novartis Ag Derivados de pirazolo-pirrolidin-4-ona como inhibidores de bet y su uso en el tratamiento de enfermedades.

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012151512A2 (en) * 2011-05-04 2012-11-08 Constellation Pharmaceuticals, Inc. Bromodomain inhibitors and uses thereof
WO2012174487A2 (en) * 2011-06-17 2012-12-20 Constellation Pharmaceuticals, Inc. Bromodomain inhibitors and uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Selective inhibition of BET bromodomains;Panagis Filippakopoulos,等;《Nature》;20101223;第468卷(第23期);第1067-1073页 *

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WO2014191906A1 (en) 2014-12-04
BR112015029401A2 (pt) 2017-07-25
KR20160012195A (ko) 2016-02-02
EP3004108A1 (en) 2016-04-13
JP2016520118A (ja) 2016-07-11
EA028175B1 (ru) 2017-10-31
AU2014272695A1 (en) 2015-11-26
US20160102107A1 (en) 2016-04-14
MX2015016421A (es) 2016-03-03
EA201592255A1 (ru) 2016-04-29
EP3004108B1 (en) 2017-10-18
AU2014272695B2 (en) 2016-10-20
PL3004108T3 (pl) 2018-03-30
PT3004108T (pt) 2018-01-24
US9624247B2 (en) 2017-04-18
CN105263934A (zh) 2016-01-20
CA2912986A1 (en) 2014-12-04
BR112015029401A8 (pt) 2020-03-17
ES2656471T3 (es) 2018-02-27

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