CN103168039B - 咪唑并吡啶类syk抑制剂 - Google Patents
咪唑并吡啶类syk抑制剂 Download PDFInfo
- Publication number
- CN103168039B CN103168039B CN201180023252.0A CN201180023252A CN103168039B CN 103168039 B CN103168039 B CN 103168039B CN 201180023252 A CN201180023252 A CN 201180023252A CN 103168039 B CN103168039 B CN 103168039B
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- China
- Prior art keywords
- base
- pyridine
- alkyl
- imidazo
- indazole
- 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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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic 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
- A61K31/4353—Heterocyclic 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
- A61K31/437—Heterocyclic 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
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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Families Citing this family (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5496915B2 (ja) | 2008-02-13 | 2014-05-21 | シージーアイ ファーマシューティカルズ,インコーポレーテッド | 6−アリール−イミダゾ[1,2−a]ピラジン誘導体、その製造方法、及びその使用方法 |
JP5696052B2 (ja) | 2008-12-08 | 2015-04-08 | ギリアード コネチカット, インコーポレイテッド | イミダゾピラジンsyk阻害剤 |
HUE030427T2 (en) | 2008-12-08 | 2017-05-29 | Gilead Connecticut Inc | Imidazopyrazine Syk inhibitors |
NZ602362A (en) | 2010-03-11 | 2014-11-28 | Gilead Connecticut Inc | Imidazopyridines syk inhibitors |
WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
RU2628616C2 (ru) * | 2011-11-03 | 2017-08-21 | Ф. Хоффманн-Ля Рош Аг | Бициклические соединения пиперазина |
CN107383009B (zh) | 2012-06-13 | 2020-06-09 | 因塞特控股公司 | 作为fgfr抑制剂的取代的三环化合物 |
US20130338142A1 (en) * | 2012-06-14 | 2013-12-19 | Gilead Connecticut, Inc. | Imidazopyrazine syk inhibitors |
WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
CN102898426B (zh) * | 2012-11-15 | 2015-04-22 | 江苏先声药业有限公司 | 抑制igf-1r酪氨酸激酶活性的吡啶并吡唑类衍生物 |
US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
SG11201508328PA (en) | 2013-04-19 | 2015-11-27 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
TW201602108A (zh) | 2013-07-30 | 2016-01-16 | 吉李德康乃狄克公司 | 脾酪胺酸激酶(Syk)抑制劑之多晶型 |
AP2016009007A0 (en) | 2013-07-30 | 2016-01-31 | Gilead Connecticut Inc | Formulation of syk inhibitors |
US9376441B2 (en) | 2013-07-31 | 2016-06-28 | Gilead Sciences, Inc. | Substituted pyrrolidines as SYK inhibitors |
PT3076976T (pt) | 2013-12-04 | 2020-12-07 | Kronos Bio Inc | Métodos para tratar cancros |
UY35898A (es) | 2013-12-23 | 2015-07-31 | Gilead Sciences Inc | ?compuestos inhibidores de syk y composiciones que los comprenden?. |
US9290505B2 (en) | 2013-12-23 | 2016-03-22 | Gilead Sciences, Inc. | Substituted imidazo[1,2-a]pyrazines as Syk inhibitors |
WO2015157955A1 (en) * | 2014-04-17 | 2015-10-22 | Abbvie Inc. | Heterocyclic btk inhibit ors |
TW201617074A (zh) * | 2014-07-14 | 2016-05-16 | 吉李德科學股份有限公司 | Syk(脾酪胺酸激酶)抑制劑 |
KR20170029580A (ko) | 2014-07-14 | 2017-03-15 | 길리애드 사이언시즈, 인코포레이티드 | 암을 치료하기 위한 조합물 |
US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
CN107438607B (zh) | 2015-02-20 | 2021-02-05 | 因赛特公司 | 作为fgfr抑制剂的双环杂环 |
EP3386993A1 (de) * | 2015-12-10 | 2018-10-17 | Bayer Pharma Aktiengesellschaft | Substituierte perhydropyrrolo[3,4-c]pyrrol-derivate und ihre verwendung |
EP3512519A1 (en) | 2016-09-14 | 2019-07-24 | Gilead Sciences, Inc. | Syk inhibitors |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
JP7299167B2 (ja) * | 2017-06-14 | 2023-06-27 | チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド | Syk阻害薬及びその使用方法 |
KR102399996B1 (ko) | 2017-08-25 | 2022-05-20 | 길리애드 사이언시즈, 인코포레이티드 | Syk 억제제의 다형체 |
AU2019262195B2 (en) | 2018-05-04 | 2024-09-12 | Incyte Corporation | Solid forms of an FGFR inhibitor and processes for preparing the same |
CA3099116A1 (en) | 2018-05-04 | 2019-11-07 | Incyte Corporation | Salts of an fgfr inhibitor |
EP3886854A4 (en) | 2018-11-30 | 2022-07-06 | Nuvation Bio Inc. | PYRROLE AND PYRAZOLE COMPOUNDS AND METHODS OF USE THERE |
JP2022521413A (ja) | 2019-02-22 | 2022-04-07 | クロノス バイオ インコーポレイテッド | Syk阻害剤としての縮合ピラジンの固体形態 |
US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
CA3129665A1 (en) | 2019-03-21 | 2020-09-24 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
CN110183471B (zh) * | 2019-05-21 | 2022-02-15 | 江苏大学 | 一种哌嗪类衍生物及制备方法及应用 |
WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
JP2022552324A (ja) | 2019-10-14 | 2022-12-15 | インサイト・コーポレイション | Fgfr阻害剤としての二環式複素環 |
US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
CN114761006A (zh) | 2019-11-08 | 2022-07-15 | Inserm(法国国家健康医学研究院) | 对激酶抑制剂产生耐药性的癌症的治疗方法 |
CA3163875A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
KR20220131900A (ko) | 2019-12-04 | 2022-09-29 | 인사이트 코포레이션 | Fgfr 억제제의 유도체 |
WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
CN112010879B (zh) * | 2020-09-15 | 2021-07-02 | 山西大学 | 一种Zn功能配合物及其制备方法和应用 |
US12065494B2 (en) | 2021-04-12 | 2024-08-20 | Incyte Corporation | Combination therapy comprising an FGFR inhibitor and a Nectin-4 targeting agent |
JP2024522189A (ja) | 2021-06-09 | 2024-06-11 | インサイト・コーポレイション | Fgfr阻害剤としての三環式ヘテロ環 |
CN113636973B (zh) * | 2021-09-07 | 2023-04-07 | 山东铂源药业股份有限公司 | 一种4-(6-氨基吡啶-3-基)哌嗪-1-羧酸叔丁酯的工业化制备方法 |
Family Cites Families (74)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
US4326525A (en) | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
US5364620A (en) | 1983-12-22 | 1994-11-15 | Elan Corporation, Plc | Controlled absorption diltiazem formulation for once daily administration |
US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
FR2607813B1 (fr) | 1986-12-05 | 1989-03-31 | Montpellier I Universite | Alkylamino-8 imidazo (1,2-a) pyrazines et derives, leur preparation et leur application en therapeutique |
US5001139A (en) | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
US4992445A (en) | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
US4902514A (en) | 1988-07-21 | 1990-02-20 | Alza Corporation | Dosage form for administering nilvadipine for treating cardiovascular symptoms |
US5137876A (en) | 1990-10-12 | 1992-08-11 | Merck & Co., Inc. | Nucleoside antiviral and anti-inflammatory compounds and compositions and methods for using same |
DE4327027A1 (de) | 1993-02-15 | 1994-08-18 | Bayer Ag | Imidazoazine |
DE4337609A1 (de) | 1993-11-04 | 1995-05-11 | Boehringer Ingelheim Kg | Neue Pyrazincarboxamidderivate, ihre Herstellung und ihre Verwendung in Arzneimitteln |
DE4337611A1 (de) | 1993-11-04 | 1995-05-11 | Boehringer Ingelheim Kg | Neue Benzoylguanidine, ihre Herstellung und ihre Verwendung in Arzneimitteln |
FR2711993B1 (fr) | 1993-11-05 | 1995-12-01 | Rhone Poulenc Rorer Sa | Médicaments contenant des dérivés de 7H-imidazol[1,2-a]pyrazine-8-one, les nouveaux composés et leur préparation. |
ATE372966T1 (de) | 1994-03-25 | 2007-09-15 | Isotechnika Inc | Verbesserung der effektivität von arzneimitteln duren deuterierung |
US6334997B1 (en) | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
FR2723373B1 (fr) | 1994-08-02 | 1996-09-13 | Rhone Poulenc Rorer Sa | Forme purifiee de streptogramines, sa preparation et les compositions pharmaceutiques qui la contiennent |
JPH11505524A (ja) | 1995-05-01 | 1999-05-21 | 藤沢薬品工業株式会社 | イミダゾ1,2−aピリジンおよびイミダゾ1,2−aピリデジン誘導体、および骨吸収阻害剤としてのその用途 |
US5593997A (en) | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
SE9704404D0 (sv) | 1997-11-28 | 1997-11-28 | Astra Ab | New compounds |
KR100834809B1 (ko) * | 1999-01-25 | 2008-06-05 | 바이오겐 아이덱 엠에이 인코포레이티드 | Baff, 관련 차단제 및 면역 반응에서 b 세포와면역글로불린을 촉진 및 억제하는데에 있어서 이들의 용도 |
DE19948434A1 (de) | 1999-10-08 | 2001-06-07 | Gruenenthal Gmbh | Substanzbibliothek enthaltend bicyclische Imidazo-5-amine und/oder bicyclische Imidazo-3-amine |
JP2001302667A (ja) * | 2000-04-28 | 2001-10-31 | Bayer Ag | イミダゾピリミジン誘導体およびトリアゾロピリミジン誘導体 |
GB0018473D0 (en) | 2000-07-27 | 2000-09-13 | Merck Sharp & Dohme | Therapeutic agents |
DE10050663A1 (de) | 2000-10-13 | 2002-04-18 | Gruenenthal Gmbh | Verwendung von substituierten Imidazo[1,2-a]pyridin-, -pyrimidin- und pyrazin-3-yl-amin-Derivaten zur Herstellung von Medikamenten zur NOS-Inhibierung |
JP2004528295A (ja) | 2001-01-30 | 2004-09-16 | サイトピア ピーティワイ リミテッド | キナーゼ阻害方法 |
GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
WO2002076985A1 (en) | 2001-03-23 | 2002-10-03 | Smithkline Beecham Corporation | Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases |
BR0307735A (pt) | 2002-02-19 | 2005-01-25 | Upjohn Co | Carboxamidas heteroaromáticas com ligação-n em ponte biciclìcas fundidas para o tratamento de doença |
KR20050008691A (ko) | 2002-04-19 | 2005-01-21 | 셀룰러 지노믹스 아이엔씨 | 이미다조[1,2-a]피라진-8-일 아민, 그의 제조방법 및사용방법 |
AU2003270489A1 (en) | 2002-09-09 | 2004-03-29 | Cellular Genomics, Inc. | 6-ARYL-IMIDAZO(1,2-a)PYRAZIN-8-YLAMINES, METHOD OF MAKING, AND METHOD OF USE THEREOF |
KR20050052500A (ko) * | 2002-09-19 | 2005-06-02 | 쉐링 코포레이션 | 사이클린 의존성 키나제 억제제로서의 이미다조피리딘 |
TW200412967A (en) | 2002-09-23 | 2004-08-01 | Schering Corp | Novel imidazopyrazines as cyclin dependent kinase inhibitors |
KR20050057520A (ko) | 2002-09-23 | 2005-06-16 | 쉐링 코포레이션 | 사이클린 의존성 키나제 억제제로서의 이미다조피라진 |
WO2004072081A1 (en) | 2003-02-10 | 2004-08-26 | Cellular Genomics, Inc. | Certain 8-heteroaryl-6-phenyl-imidazo[1,2-a]pyrazines as modulators of kinase activity |
AR043002A1 (es) | 2003-02-18 | 2005-07-13 | Altana Pharma Ag | Imidazopirazinas 6-substituidos |
US7157460B2 (en) | 2003-02-20 | 2007-01-02 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
US7186832B2 (en) | 2003-02-20 | 2007-03-06 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
US7405295B2 (en) | 2003-06-04 | 2008-07-29 | Cgi Pharmaceuticals, Inc. | Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of Bruton's tyrosine kinase by such compounds |
US20060183746A1 (en) | 2003-06-04 | 2006-08-17 | Currie Kevin S | Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of Bruton's tyrosine kinase by such compounds |
WO2005005429A1 (en) | 2003-06-30 | 2005-01-20 | Cellular Genomics, Inc. | Certain heterocyclic substituted imidazo[1,2-a]pyrazin-8-ylamines and methods of inhibition of bruton’s tyrosine kinase by such compounds |
WO2005019220A2 (en) | 2003-08-11 | 2005-03-03 | Cellular Genomics Inc. | Substituted imidazo[1,2-a]pyrazines as modulators of kinase activity |
US7144907B2 (en) * | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
WO2005047290A2 (en) * | 2003-11-11 | 2005-05-26 | Cellular Genomics Inc. | Imidazo[1,2-a] pyrazin-8-ylamines as kinase inhibitors |
WO2005085252A1 (en) | 2004-03-04 | 2005-09-15 | Biofocus Discovery Limited | Imidazo ‘1,2-a’ pyrazine compounds which interact with protein kinases |
US7713973B2 (en) | 2004-10-15 | 2010-05-11 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
BRPI0517619A (pt) | 2004-11-10 | 2008-10-14 | Cgi Pharmaceuticals Inc | entidades quìmicas de imidazo[1,2-a] pirazin-8-ilaminas, suas composições farmacêuticas, uso dos referidos compostos na preparação de medicamento, processo de preparação de medicamento e métodos de utilização dos referidos compostos |
WO2007008541A2 (en) | 2005-07-08 | 2007-01-18 | Kalypsys, Inc. | Cellular cholesterol absorption modifiers |
JP2009515882A (ja) | 2005-11-10 | 2009-04-16 | シェーリング コーポレイション | プロテインキナーゼを阻害するための方法 |
AR056785A1 (es) | 2005-11-10 | 2007-10-24 | Schering Corp | COMPUESTOS DE IMIDAZO[1,2-A]PIRAZINAS, uTILES COMO INHIBIDORES, REGULADORES O MODULADORES DE PROTEINQUINASAS |
AU2007291190A1 (en) * | 2006-08-30 | 2008-03-06 | Cellzome Limited | Triazole derivatives as kinase inhibitors |
US7951818B2 (en) * | 2006-12-01 | 2011-05-31 | Galapagos Nv | Imidazolopyridine compounds useful for the treatment of degenerative and inflammatory diseases |
WO2009077334A1 (en) | 2007-12-14 | 2009-06-25 | F. Hoffmann-La Roche Ag | Novel imidazo[1,2-a]pyridine and imidazo[1,2-b]pyridazine derivatives |
JP5496915B2 (ja) | 2008-02-13 | 2014-05-21 | シージーアイ ファーマシューティカルズ,インコーポレーテッド | 6−アリール−イミダゾ[1,2−a]ピラジン誘導体、その製造方法、及びその使用方法 |
JP2011525183A (ja) * | 2008-06-20 | 2011-09-15 | ブリストル−マイヤーズ スクイブ カンパニー | キナーゼ阻害剤として有用なイミダゾピリジンおよびイミダゾピラジン化合物 |
CN102066370B (zh) * | 2008-07-15 | 2014-05-14 | 霍夫曼-拉罗奇有限公司 | 苯基-咪唑并吡啶类和哒嗪类 |
TWI453207B (zh) * | 2008-09-08 | 2014-09-21 | Signal Pharm Llc | 胺基三唑并吡啶,其組合物及使用其之治療方法 |
WO2010038257A1 (ja) * | 2008-09-30 | 2010-04-08 | 株式会社アドバンテスト | プログラマブルデバイス、およびデータ書込方法 |
US8450321B2 (en) | 2008-12-08 | 2013-05-28 | Gilead Connecticut, Inc. | 6-(1H-indazol-6-yl)-N-[4-(morpholin-4-yl)phenyl]imidazo-[1,2-A]pyrazin-8-amine, or a pharmaceutically acceptable salt thereof, as a SYK inhibitor |
JP5696052B2 (ja) | 2008-12-08 | 2015-04-08 | ギリアード コネチカット, インコーポレイテッド | イミダゾピラジンsyk阻害剤 |
HUE030427T2 (en) | 2008-12-08 | 2017-05-29 | Gilead Connecticut Inc | Imidazopyrazine Syk inhibitors |
NZ602362A (en) | 2010-03-11 | 2014-11-28 | Gilead Connecticut Inc | Imidazopyridines syk inhibitors |
US20140148430A1 (en) | 2012-11-26 | 2014-05-29 | Gilead Connecticut, Inc. | Imidazopyridines syk inhibitors |
AP2016009007A0 (en) | 2013-07-30 | 2016-01-31 | Gilead Connecticut Inc | Formulation of syk inhibitors |
TW201602108A (zh) | 2013-07-30 | 2016-01-16 | 吉李德康乃狄克公司 | 脾酪胺酸激酶(Syk)抑制劑之多晶型 |
US9376441B2 (en) | 2013-07-31 | 2016-06-28 | Gilead Sciences, Inc. | Substituted pyrrolidines as SYK inhibitors |
PT3076976T (pt) | 2013-12-04 | 2020-12-07 | Kronos Bio Inc | Métodos para tratar cancros |
UY35898A (es) | 2013-12-23 | 2015-07-31 | Gilead Sciences Inc | ?compuestos inhibidores de syk y composiciones que los comprenden?. |
US9290505B2 (en) | 2013-12-23 | 2016-03-22 | Gilead Sciences, Inc. | Substituted imidazo[1,2-a]pyrazines as Syk inhibitors |
TW201617074A (zh) | 2014-07-14 | 2016-05-16 | 吉李德科學股份有限公司 | Syk(脾酪胺酸激酶)抑制劑 |
KR20170029580A (ko) | 2014-07-14 | 2017-03-15 | 길리애드 사이언시즈, 인코포레이티드 | 암을 치료하기 위한 조합물 |
TW201639573A (zh) | 2015-02-03 | 2016-11-16 | 吉李德科學股份有限公司 | 有關治療癌症之合併治療 |
JP2018513173A (ja) | 2015-04-21 | 2018-05-24 | ギリアード サイエンシーズ, インコーポレイテッド | Syk阻害剤を用いた慢性移植片対宿主病の処置 |
TW201822764A (zh) | 2016-09-14 | 2018-07-01 | 美商基利科學股份有限公司 | Syk抑制劑 |
EP3512519A1 (en) | 2016-09-14 | 2019-07-24 | Gilead Sciences, Inc. | Syk inhibitors |
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CA2792769A1 (en) | 2011-09-15 |
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MX2012010418A (es) | 2013-01-14 |
JP6177828B2 (ja) | 2017-08-09 |
PT2545052E (pt) | 2015-02-18 |
HK1180689A1 (en) | 2013-10-25 |
AU2011226689B2 (en) | 2016-09-01 |
US20190117679A1 (en) | 2019-04-25 |
KR101717809B1 (ko) | 2017-03-17 |
US20130210802A1 (en) | 2013-08-15 |
CN103168039A (zh) | 2013-06-19 |
US10842803B2 (en) | 2020-11-24 |
NZ602362A (en) | 2014-11-28 |
AU2018203210A1 (en) | 2018-05-31 |
CA2792769C (en) | 2018-05-22 |
US9562056B2 (en) | 2017-02-07 |
AU2011226689A1 (en) | 2012-09-27 |
EP2545052A1 (en) | 2013-01-16 |
JP2013522238A (ja) | 2013-06-13 |
EP2545052B1 (en) | 2014-11-12 |
BR112012022943A2 (pt) | 2018-06-05 |
ES2530449T3 (es) | 2015-03-02 |
WO2011112995A1 (en) | 2011-09-15 |
JP2017222685A (ja) | 2017-12-21 |
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