ES2563445T3 - Ligadores P1 cíclicos como inhibidores del factor XIa - Google Patents
Ligadores P1 cíclicos como inhibidores del factor XIa Download PDFInfo
- Publication number
- ES2563445T3 ES2563445T3 ES12766737.6T ES12766737T ES2563445T3 ES 2563445 T3 ES2563445 T3 ES 2563445T3 ES 12766737 T ES12766737 T ES 12766737T ES 2563445 T3 ES2563445 T3 ES 2563445T3
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- group
- alkyl
- halogen
- mmol
- intermediary
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- 239000003112 inhibitor Substances 0.000 title description 58
- 108010080805 Factor XIa Proteins 0.000 title description 36
- 125000004122 cyclic group Chemical group 0.000 title description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 267
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 206
- 150000001875 compounds Chemical class 0.000 claims abstract description 203
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 80
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 68
- 150000002367 halogens Chemical class 0.000 claims abstract description 68
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 61
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 45
- 239000012453 solvate Substances 0.000 claims abstract description 43
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 33
- 125000003118 aryl group Chemical group 0.000 claims abstract description 31
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 28
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 27
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 25
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 21
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 18
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 12
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 35
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 33
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- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 8
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims description 7
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
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- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 3
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 17
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- 235000019439 ethyl acetate Nutrition 0.000 description 79
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- 235000002639 sodium chloride Nutrition 0.000 description 65
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- 239000012044 organic layer Substances 0.000 description 58
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
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Classifications
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- C07D487/02—Heterocyclic 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
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- A—HUMAN NECESSITIES
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- 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
- 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
- C07D471/06—Peri-condensed systems
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- 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
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic 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
- C07D487/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
Landscapes
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- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
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| PCT/US2012/049698 WO2013022814A1 (en) | 2011-08-05 | 2012-08-06 | Cyclic p1 linkers as factor xia inhibitors |
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| NZ602266A (en) | 2010-02-11 | 2014-05-30 | Bristol Myers Squibb Co | Macrocycles as factor xia inhibitors |
| TW201319068A (zh) | 2011-08-05 | 2013-05-16 | 必治妥美雅史谷比公司 | 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑 |
| TW201311689A (zh) | 2011-08-05 | 2013-03-16 | 必治妥美雅史谷比公司 | 作為因子ｘｉａ抑制劑之新穎巨環化合物 |
| WO2013055984A1 (en) | 2011-10-14 | 2013-04-18 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| JP6033319B2 (ja) | 2011-10-14 | 2016-11-30 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物 |
| AU2013296259A1 (en) * | 2012-08-03 | 2015-03-19 | Bristol-Myers Squibb Company | Dihydropyridone P1 as factor XIa inhibitors |
| US9376444B2 (en) * | 2012-08-03 | 2016-06-28 | Bristol-Myers Squibb Company | Dihydropyridone P1 as factor XIa inhibitors |
| US9403774B2 (en) | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| TR201807316T4 (tr) | 2012-10-12 | 2018-06-21 | Bristol Myers Squibb Co | Bir faktör XIa inhibitörünün kristalli formları. |
| EP2906552B1 (en) | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| WO2014160668A1 (en) | 2013-03-25 | 2014-10-02 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
| WO2014160592A2 (en) | 2013-03-27 | 2014-10-02 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| SG10201908467RA (en) * | 2014-01-31 | 2019-10-30 | Bristol Myers Squibb Co | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
| NO2760821T3 (https=) * | 2014-01-31 | 2018-03-10 | ||
| US9663527B2 (en) | 2014-02-11 | 2017-05-30 | Merck Sharp & Dohme Corp. | Factor XIa inhibitors |
| WO2015123093A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| WO2015123091A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| EP3134408B1 (en) | 2014-04-22 | 2020-08-12 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| WO2016015593A1 (en) | 2014-07-28 | 2016-02-04 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| ES2714283T3 (es) | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
| NO2721243T3 (https=) | 2014-10-01 | 2018-10-20 | ||
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| BR112017012146B1 (pt) * | 2014-12-10 | 2023-11-21 | Ono Pharmaceutical Co., Ltd | Composto derivado de di-hidroindolizinona, seu uso, composição farmacêutica e inibidor de fxia |
| ES2762987T3 (es) * | 2015-06-19 | 2020-05-26 | Bristol Myers Squibb Co | Macrociclos de diamida como inhibidores del factor XIA |
| JP6629958B2 (ja) | 2015-07-29 | 2020-01-15 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | アルキルまたはシクロアルキルＰ２’基を担持する大員環の第ＸＩａ因子阻害剤 |
| CN114874222B (zh) | 2015-07-29 | 2025-06-06 | 百时美施贵宝公司 | 携带非芳族p2,基团的因子xia新大环 |
| EP3368036B1 (en) | 2015-10-29 | 2022-07-20 | Merck Sharp & Dohme LLC | Macrocyclic pyridine-n-oxide derivatives as factor xia inhibitors |
| EP3371162B1 (en) | 2015-10-29 | 2022-01-26 | Merck Sharp & Dohme Corp. | Macrocyclic spirocarbamate derivatives as factor xia inhibitors, pharmaceutically acceptable compositions and their use |
| KR20180117156A (ko) | 2016-03-02 | 2018-10-26 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 XIa 억제 활성을 갖는 디아미드 마크로사이클 |
| WO2018039094A1 (en) | 2016-08-22 | 2018-03-01 | Merck Sharp & Dohme Corp. | Pyridine-1-oxide derivatives and their use as factor xia inhibitors |
| EP3301094A1 (en) * | 2016-09-30 | 2018-04-04 | Mutabilis | Heterocyclic compounds and their use in preventing or treating bacterial infections |
| CN110062757B (zh) * | 2017-01-18 | 2022-03-04 | 广东东阳光药业有限公司 | 凝血因子XIa抑制剂及其用途 |
| WO2019011166A1 (zh) * | 2017-07-14 | 2019-01-17 | 四川科伦博泰生物医药股份有限公司 | 大环酰胺化合物及其药物组合物和用途 |
| HUE062236T2 (hu) * | 2018-04-17 | 2023-10-28 | Univ Michigan Regents | Vérlemezke funkció inhibitorok és eljárás azok alkalmazására |
| WO2020211781A1 (zh) | 2019-04-16 | 2020-10-22 | 南京明德新药研发有限公司 | 作为XIa因子抑制剂的大环衍生物 |
| CN114008047B (zh) | 2019-07-23 | 2023-03-21 | 南京明德新药研发有限公司 | 作为XIa因子抑制剂的大环衍生物 |
| CN115490708B (zh) * | 2021-06-18 | 2025-01-24 | 苏州亚盛药业有限公司 | 磺酰胺类大环衍生物及其制备方法和用途 |
| KR20260032556A (ko) * | 2023-06-30 | 2026-03-09 | 심천 사루브리스 퍼머수티칼스 컴퍼니 리미티드 | 다치환된 거대환식 화합물 및 이의 제조 방법과 용도 |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0028489B1 (en) | 1979-11-05 | 1983-10-05 | Beecham Group Plc | Enzyme derivatives, and their preparation |
| JPH0987280A (ja) * | 1995-09-28 | 1997-03-31 | Yamanouchi Pharmaceut Co Ltd | オキソピペラジン誘導体又はその塩 |
| PE121699A1 (es) | 1997-02-18 | 1999-12-08 | Boehringer Ingelheim Pharma | Heterociclos biciclicos disustituidos como inhibidores de la trombina |
| ZA985247B (en) | 1997-06-19 | 1999-12-17 | Du Pont Merck Pharma | Guanidine mimics as factor Xa inhibitors. |
| WO2000077027A2 (en) | 1999-06-14 | 2000-12-21 | Tularik Limited | Serine protease inhibitors |
| DE19962924A1 (de) | 1999-12-24 | 2001-07-05 | Bayer Ag | Substituierte Oxazolidinone und ihre Verwendung |
| AR035216A1 (es) | 2000-12-01 | 2004-05-05 | Astrazeneca Ab | Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios |
| AU2002322802A1 (en) * | 2001-07-27 | 2003-02-17 | Merck And Co., Inc. | Thrombin inhibitors |
| CN104744461A (zh) | 2001-09-21 | 2015-07-01 | 百时美施贵宝公司 | 含有内酰胺的化合物及其衍生物作为Xa因子的抑制剂 |
| US20040180855A1 (en) | 2003-02-19 | 2004-09-16 | Schumacher William A. | Methods of treating thrombosis with reduced risk of increased bleeding times |
| US7138412B2 (en) | 2003-03-11 | 2006-11-21 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives useful as serine protease inhibitors |
| US7129264B2 (en) | 2003-04-16 | 2006-10-31 | Bristol-Myers Squibb Company | Biarylmethyl indolines and indoles as antithromboembolic agents |
| US7417063B2 (en) | 2004-04-13 | 2008-08-26 | Bristol-Myers Squibb Company | Bicyclic heterocycles useful as serine protease inhibitors |
| US7429604B2 (en) | 2004-06-15 | 2008-09-30 | Bristol Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| US7453002B2 (en) | 2004-06-15 | 2008-11-18 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
| EP1841504B1 (en) | 2005-01-13 | 2014-11-19 | Bristol-Myers Squibb Company | Substituted biaryl compounds as factor xia inhibitors |
| US20060183771A1 (en) | 2005-02-17 | 2006-08-17 | Seiffert Dietmar A | Novel combination of selective factor VIIa and/or factor XIa inhibitors and selective plasma kallikrein inhibitors |
| NZ568595A (en) | 2005-12-14 | 2010-04-30 | Bristol Myers Squibb Co | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor Xla inhibitors |
| WO2007070816A2 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Thiophene derivatives as factor xia inhibitors |
| EP1966141A1 (en) | 2005-12-14 | 2008-09-10 | Brystol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| CN101389613B (zh) * | 2005-12-23 | 2011-10-12 | 布里斯托尔-迈尔斯.斯奎布公司 | 用作抗凝血药的大环凝血因子viia抑制剂 |
| PE20071132A1 (es) * | 2005-12-23 | 2007-12-14 | Bristol Myers Squibb Co | Compuestos macrociclicos como inhibidores del factor viia |
| EP2102189B1 (en) | 2006-12-15 | 2015-07-29 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors |
| CN101784516B (zh) | 2007-06-13 | 2014-07-02 | 百时美施贵宝公司 | 作为凝血因子抑制剂的二肽类似物 |
| EP2070899A1 (en) | 2007-12-14 | 2009-06-17 | F. Hoffmann-La Roche Ag | Deprotection of N-BOC compounds |
| US8324199B2 (en) * | 2008-03-13 | 2012-12-04 | Bristol-Myers Squibb Company | Pyridazine derivatives as factor xia inhibitors |
| NZ602266A (en) * | 2010-02-11 | 2014-05-30 | Bristol Myers Squibb Co | Macrocycles as factor xia inhibitors |
| TW201311689A (zh) | 2011-08-05 | 2013-03-16 | 必治妥美雅史谷比公司 | 作為因子ｘｉａ抑制劑之新穎巨環化合物 |
| TW201319068A (zh) | 2011-08-05 | 2013-05-16 | 必治妥美雅史谷比公司 | 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑 |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| JP6033319B2 (ja) | 2011-10-14 | 2016-11-30 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物 |
| WO2013055984A1 (en) | 2011-10-14 | 2013-04-18 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| US9376444B2 (en) | 2012-08-03 | 2016-06-28 | Bristol-Myers Squibb Company | Dihydropyridone P1 as factor XIa inhibitors |
| AU2013296259A1 (en) | 2012-08-03 | 2015-03-19 | Bristol-Myers Squibb Company | Dihydropyridone P1 as factor XIa inhibitors |
| US9403774B2 (en) | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| TR201807316T4 (tr) | 2012-10-12 | 2018-06-21 | Bristol Myers Squibb Co | Bir faktör XIa inhibitörünün kristalli formları. |
| EP2906552B1 (en) | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
-
2012
- 2012-08-03 TW TW101128158A patent/TW201319068A/zh unknown
- 2012-08-06 CN CN201280037801.4A patent/CN103702999B/zh active Active
- 2012-08-06 CN CN201510648908.8A patent/CN105294701B/zh active Active
- 2012-08-06 US US14/236,968 patent/US8901115B2/en active Active
- 2012-08-06 WO PCT/US2012/049698 patent/WO2013022814A1/en not_active Ceased
- 2012-08-06 ES ES12766737.6T patent/ES2563445T3/es active Active
- 2012-08-06 EP EP16151754.5A patent/EP3070087B1/en active Active
- 2012-08-06 ES ES16151754T patent/ES2733096T3/es active Active
- 2012-08-06 JP JP2014524151A patent/JP6113727B2/ja active Active
- 2012-08-06 EP EP12766737.6A patent/EP2739625B1/en active Active
- 2012-08-07 AR ARP120102879A patent/AR088423A1/es unknown
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2014
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Also Published As
| Publication number | Publication date |
|---|---|
| EP3070087B1 (en) | 2019-04-10 |
| CN105294701A (zh) | 2016-02-03 |
| US8901115B2 (en) | 2014-12-02 |
| US20150057262A1 (en) | 2015-02-26 |
| CN103702999A (zh) | 2014-04-02 |
| AR088423A1 (es) | 2014-06-11 |
| US9108981B2 (en) | 2015-08-18 |
| TW201319068A (zh) | 2013-05-16 |
| WO2013022814A1 (en) | 2013-02-14 |
| EP2739625B1 (en) | 2016-01-20 |
| JP2014521700A (ja) | 2014-08-28 |
| EP3070087A1 (en) | 2016-09-21 |
| CN105294701B (zh) | 2017-10-24 |
| EP2739625A1 (en) | 2014-06-11 |
| JP6113727B2 (ja) | 2017-04-12 |
| ES2733096T3 (es) | 2019-11-27 |
| US20140163002A1 (en) | 2014-06-12 |
| CN103702999B (zh) | 2015-11-25 |
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