CN103443082B - Lxr调节性咪唑衍生物的前药 - Google Patents

Lxr调节性咪唑衍生物的前药 Download PDF

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Publication number
CN103443082B
CN103443082B CN201280014836.6A CN201280014836A CN103443082B CN 103443082 B CN103443082 B CN 103443082B CN 201280014836 A CN201280014836 A CN 201280014836A CN 103443082 B CN103443082 B CN 103443082B
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compound
disease
compounds
solvent
biphenyl
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Expired - Fee Related
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Chinese (zh)
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CN103443082A (zh
Inventor
E.K.基克
M.J.黑格曼
V.R.瓜里诺
C-C.苏
魏正国
J.S.沃里尔
S.K.奈尔
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Exelixis Inc
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Bristol Myers Squibb Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • 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
    • A61K31/41—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
    • A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/12—Esters of phosphoric acids with hydroxyaryl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Neurosurgery (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Psychiatry (AREA)
  • Vascular Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Urology & Nephrology (AREA)
  • Emergency Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
CN201280014836.6A 2011-03-25 2012-03-26 Lxr调节性咪唑衍生物的前药 Expired - Fee Related CN103443082B (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161467404P 2011-03-25 2011-03-25
US61/467,404 2011-03-25
US61/467404 2011-03-25
PCT/US2012/030499 WO2012135082A1 (en) 2011-03-25 2012-03-26 Prodrugs of lxr modulating imidazole derivatives

Publications (2)

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CN103443082A CN103443082A (zh) 2013-12-11
CN103443082B true CN103443082B (zh) 2015-11-25

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Country Link
US (1) US8901106B2 (https=)
EP (1) EP2688871B1 (https=)
JP (1) JP2014510110A (https=)
CN (1) CN103443082B (https=)
AR (1) AR088728A1 (https=)
ES (1) ES2548050T3 (https=)
TW (1) TW201242953A (https=)
WO (1) WO2012135082A1 (https=)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2820013T3 (en) 2012-03-02 2018-10-29 Ralexar Therapeutics Inc Liver X Receptor (LXR) modulators for the treatment of dermal diseases, disorders and conditions
EP3626309B1 (en) 2012-08-13 2023-03-08 The Rockefeller University Lxrbeta agonist for the treatment of cancer
JP6442475B2 (ja) * 2013-03-15 2018-12-19 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｌｘｒ調節因子
JP2016532713A (ja) 2013-09-04 2016-10-20 アレクサー セラピューティクス， インク． 肝臓ｘ受容体（ｌｘｒ）調節因子
PT3041835T (pt) 2013-09-04 2020-07-13 Ellora Therapeutics Inc Moduladores de recetor de fígado x (lxr)
US10669296B2 (en) 2014-01-10 2020-06-02 Rgenix, Inc. LXR agonists and uses thereof
MX380578B (es) 2014-10-03 2025-03-12 Ucb Biopharma Sprl Derivados de imidazol pentaciclicos fusionados.
CA3010883A1 (en) 2016-01-11 2017-07-20 The Rockefeller University Methods for the treatment of myeloid derived suppressor cells related disorders
EA201892153A1 (ru) 2016-04-01 2019-04-30 Юсб Байофарма Спрл Конденсированные пентациклические производные имидазола в качестве модуляторов активности tnf
JP6968090B2 (ja) 2016-04-01 2021-11-17 ユーシービー バイオファルマ エスアールエル Ｔｎｆ活性のモジュレーターとしての縮合五環式イミダゾール誘導体
US10766906B2 (en) 2016-04-01 2020-09-08 UCB Biopharma SRL Fused hexacyclic imidazole derivatives as modulators of TNF activity
EP3436458B1 (en) 2016-04-01 2021-06-02 UCB Biopharma SRL Fused pentacyclic imidazole derivatives as modulators of tnf activity
AU2017246228B2 (en) * 2016-04-04 2021-04-15 Chemocentryx, Inc. Soluble C5aR antagonists
CN110461842A (zh) 2017-03-15 2019-11-15 Ucb生物制药私人有限公司 作为tnf活性调节剂的稠合五环咪唑衍生物
EP3713575A4 (en) 2017-11-21 2021-08-25 Rgenix, Inc. POLYMORPHS AND THEIR USES
HUE067466T2 (hu) 2019-12-13 2024-10-28 Inspirna Inc Fémsók és alkalmazásuk

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007002563A1 (en) * 2005-06-27 2007-01-04 Exelixis, Inc. Imidazole based lxr modulators
CN101248049A (zh) * 2005-06-27 2008-08-20 埃克塞利希斯股份有限公司 咪唑类lxr调节剂
CN101679297A (zh) * 2006-12-08 2010-03-24 埃克塞利希斯股份有限公司 Lxr和fxr调节剂
WO2010138598A2 (en) * 2009-05-28 2010-12-02 Exelixis, Inc. Lxr modulators

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4231938A (en) 1979-06-15 1980-11-04 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4444784A (en) 1980-08-05 1984-04-24 Merck & Co., Inc. Antihypercholesterolemic compounds
MX7065E (es) 1980-06-06 1987-04-10 Sankyo Co Un procedimiento microbiologico para preparar derivados de ml-236b
HU204253B (en) 1982-11-22 1991-12-30 Sandoz Ag Process for producing mevalonolactone analogues and derivatives and pharmaceutical compositions containing them
US5354772A (en) 1982-11-22 1994-10-11 Sandoz Pharm. Corp. Indole analogs of mevalonolactone and derivatives thereof
FI94339C (fi) 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
US5177080A (en) 1990-12-14 1993-01-05 Bayer Aktiengesellschaft Substituted pyridyl-dihydroxy-heptenoic acid and its salts
WO1993006215A1 (en) 1991-09-17 1993-04-01 The Salk Institute For Biological Studies Receptor of the thyroid/steroid hormone receptor superfamily
WO1998032444A1 (en) 1997-01-24 1998-07-30 The Regents Of The University Of California USE OF FXR, PPARα AND LXRα ACTIVATORS TO RESTORE BARRIER FUNCTION, PROMOTE EPIDERMAL DIFFERENTIATION AND INHIBIT PROLIFERATION
US5767134A (en) * 1997-05-15 1998-06-16 Vion Pharmaceuticals, Inc. Prodrug forms of ribonucleotide reductase inhibitors 3-AP and 3-AMP
EP1115853A2 (en) 1998-09-23 2001-07-18 Ludmila Solomin Analysis of ligand activated nuclear receptors in vivo
DE69940958D1 (de) 1998-12-23 2009-07-16 Glaxo Group Ltd Bestimmungsmethode fur liganden der nuklearen rezeptoren
US6071955A (en) 1999-02-25 2000-06-06 The Regents Of The University Of California FXR, PPARA and LXRA activators to treat acne/acneiform conditions
US6316503B1 (en) 1999-03-15 2001-11-13 Tularik Inc. LXR modulators
AU780658B2 (en) 1999-03-26 2005-04-07 City Of Hope Method of affecting cholesterol catabolism using nuclear bile acid receptor
SG121853A1 (en) 1999-06-18 2006-05-26 Cv Therapeutics Inc Compositions and methods for increasing cholesterol efflux and raising hdl using atp binding cassette transporter protein abc1
JP2004500332A (ja) 1999-07-08 2004-01-08 テュラリク　インコーポレイテッド Ｈｄｌコレステロール値を上昇させる組成物および方法
AU2000235960A1 (en) 2000-02-14 2001-08-27 Tularik, Inc. Lxr modulators
AU2001262984A1 (en) 2000-05-03 2001-11-12 Tularik, Inc. Treatment of hypertriglyceridemia and other conditions using lxr modulators
US6924311B2 (en) 2001-10-17 2005-08-02 X-Ceptor Therapeutics, Inc. Methods for affecting various diseases utilizing LXR compounds
DE602004014806D1 (de) * 2003-10-08 2008-08-14 Smithkline Beecham Corp Triphenylethyleneverbindungen als selektive modulatoren des östrogenrezeptors
WO2006066070A2 (en) * 2004-12-17 2006-06-22 Nps Pharmaceuticals, Inc. Prodrug constructs of pyrimidinone compounds as calcilytics
US20100152238A1 (en) * 2007-03-05 2010-06-17 Yissum Research Development Company Of The Hebrew University Of Jerusalem Novel quinonoid derivatives of cannabinoids and their use in the treatment of malignancies

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007002563A1 (en) * 2005-06-27 2007-01-04 Exelixis, Inc. Imidazole based lxr modulators
CN101248049A (zh) * 2005-06-27 2008-08-20 埃克塞利希斯股份有限公司 咪唑类lxr调节剂
CN101248048A (zh) * 2005-06-27 2008-08-20 埃克塞利希斯股份有限公司 吡唑基lxr调节剂
CN101679297A (zh) * 2006-12-08 2010-03-24 埃克塞利希斯股份有限公司 Lxr和fxr调节剂
WO2010138598A2 (en) * 2009-05-28 2010-12-02 Exelixis, Inc. Lxr modulators

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Improved oral drug delivery: solubility limitations overcome by the use of prodrugs;David Fleisher等;《Advanced Drug Delivery Reviews》;19960101;第19卷;第115-130页 *
Prodrugs: design and clinical applications;Jarkko Rautio等;《nat ure reviews》;20080125;第7卷(第3期);第255-270页 *
磷酸酯类前药设计及其合成方法研究进展;杜国新,等;《中南药学》;20080228;第6卷(第1期);第82-85页 *

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EP2688871A1 (en) 2014-01-29
WO2012135082A1 (en) 2012-10-04
CN103443082A (zh) 2013-12-11
US20140018321A1 (en) 2014-01-16
EP2688871B1 (en) 2015-08-26
US8901106B2 (en) 2014-12-02
AR088728A1 (es) 2014-07-02
JP2014510110A (ja) 2014-04-24
TW201242953A (en) 2012-11-01
ES2548050T3 (es) 2015-10-13

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