AR088748A1 - Macrociclos como inhibidores del factor xia - Google Patents
Macrociclos como inhibidores del factor xiaInfo
- Publication number
- AR088748A1 AR088748A1 ARP120102878A ARP120102878A AR088748A1 AR 088748 A1 AR088748 A1 AR 088748A1 AR P120102878 A ARP120102878 A AR P120102878A AR P120102878 A ARP120102878 A AR P120102878A AR 088748 A1 AR088748 A1 AR 088748A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- heterocycle
- halogen
- nhc
- carbon atoms
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
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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
- C07D471/06—Peri-condensed systems
-
- 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
- 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
- C07D487/08—Bridged 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Estos compuestos son inhibidores selectivos del factor Xla o inhibidores duales de FXIa y calicreína plasmática. También composiciones farmacéuticas que comprenden estos compuestos y métodos para tratar trastornos tromboembólicos y/o inflamatorios mediante su uso. Reivindicación 1: Un compuesto de la fórmula (1), o un estereoisómero, un tautómero, una sal aceptable desde el punto de vista farmacéutico, un solvato de este caracterizado porque: el anillo A se selecciona de arilo y un heterociclo de 5- a 6- miembros que comprende átomos de carbono y 1 - 4 heteroátomos seleccionados de N, NH, N(alquilo C₁₋₄), S(O)ₚ y O, en donde el arilo y el heterociclo se sustituyen con R¹; el anillo B es un heterociclo de 5- a 6- miembros que comprende átomos de carbono y 1 - 4 heteroátomos seleccionados de N, NH, S(O)ₚ y O, en donde el heterociclo se sustituye opcionalmente con R¹⁰; el anillo C es un heterociclo de 4- a 5- miembros que comprende: átomos de carbono y 1 - 4 heteroátomos seleccionados de N, NR⁹, S(O)ₚ y O, en donde el heterociclo se sustituye opcionalmente con R²; X¹ se selecciona de alquileno C₁₋₄ y alquenileno C₂₋₄; opcionalmente, uno o más de los átomos de carbono del alquileno y alquenileno se pueden reemplazar por O, S(O)ₚ, NH y N(alquilo C₁₋₄); R¹, se selecciona, independientemente en cada caso, de H, halógeno, NO₂, alquilo C₁₋₆, OH, OMe y CN; R² se selecciona de H, =O, OH, NH₂, CF₃, halógeno y alquilo C₁₋₄ opcionalmente sustituido con OH; R³ se selecciona de H y alquilo C₁₋₄; alternativamente, R² y R³, junto con los átomos a los que se unen directa o indirectamente, forman un anillo que se sustituye opcionalmente con =O; R⁴ se selecciona de H, alquilo C₁₋₄, hidroxilo y cicloalquilo C₃₋₆; R⁵ se selecciona de H y alquilo C₁₋₄; R⁶ se selecciona de H, halógeno, C(O)OH y C(O)O(alquilo C₁₋₄); R⁷ se selecciona del grupo que consiste en: H, alquilo C₁₋₄ y CF₃; de manera alternativa, R⁶ y R⁷ son, en forma conjunta, =O; R⁸, se selecciona, independientemente en cada caso, de H, halógeno, NHC(O)O-alquilo C₁₋₄, CN, OH, O-alquilo C₁₋₄; CF₃, CO₂H, CO₂(alquilo C₁₋₄), -CH₂CO₂H, -(CH₂)₂CO₂H, -CH₂CO₂(alquilo C₁₋₄), -(CH₂)₂CO₂(alquilo C₁₋₄), NH₂, -CH₂NH₂, -NHCO(alquilo C₁₋₄), -NHCO₂(CH₂)₁₋₂O(alquilo C₁₋₄), -NHCO₂(CH₂)₁₋₃O(alquilo C₁₋₄), NHCO₂CH₂CH(C₁₋₄ alquil)O(alquilo C₁₋₄), -NHCO₂(CH₂)₁₋₂OH, -NHCO₂CH₂CO₂H, -CH₂NHCO₂(alquilo C₁₋₄), -NHC(O)NH(alquilo C₁₋₄), -NHC(O)N(alquilo C₁₋₄)₂, NHC(O)NH(C₁₋₄ alquil)N[heterociclo de 5- a 6- miembros)], -NHSO₂(alquilo C₁₋₄), -CONH₂, -CONH(alquilo C₁₋₄), -CON(alquilo C₁₋₄)₂ y -CH₂CONH₂; R⁹ se selecciona de H y alquilo C₁₋₄; R¹⁰, se selecciona, independientemente en cada caso, de H, halógeno, CN, =O, OH, NH₂, cicloalquilo C₃₋₆, alcoxi C₁₋₄, CF₃, CH₂OH, CO₂H, CO₂(alquilo C₁₋₄) y CONH; y p se selecciona, independientemente en cada caso, de 0, 1 y 2; siempre que los compuestos de fórmula (2) y (3) estén excluidos.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161515401P | 2011-08-05 | 2011-08-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR088748A1 true AR088748A1 (es) | 2014-07-02 |
Family
ID=46889416
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP120102878A AR088748A1 (es) | 2011-08-05 | 2012-08-07 | Macrociclos como inhibidores del factor xia |
Country Status (21)
| Country | Link |
|---|---|
| US (4) | US9221818B2 (es) |
| EP (1) | EP2739628B1 (es) |
| JP (1) | JP6158181B2 (es) |
| CN (1) | CN103857681B (es) |
| AR (1) | AR088748A1 (es) |
| BR (1) | BR112014002202A2 (es) |
| CA (1) | CA2844254A1 (es) |
| CY (1) | CY1119281T1 (es) |
| DK (1) | DK2739628T3 (es) |
| EA (1) | EA024791B1 (es) |
| ES (1) | ES2635088T3 (es) |
| HR (1) | HRP20171122T1 (es) |
| HU (1) | HUE034487T2 (es) |
| LT (1) | LT2739628T (es) |
| MX (1) | MX345763B (es) |
| PL (1) | PL2739628T3 (es) |
| PT (1) | PT2739628T (es) |
| RS (1) | RS56244B1 (es) |
| SI (1) | SI2739628T1 (es) |
| TW (1) | TW201311689A (es) |
| WO (1) | WO2013022818A1 (es) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3786165A1 (en) | 2010-02-11 | 2021-03-03 | Bristol-Myers Squibb Company | Synthetic intermediates for producing 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 |
| ES2572908T3 (es) | 2011-10-14 | 2016-06-03 | Bristol-Myers Squibb Company | Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa |
| KR101937514B1 (ko) | 2011-10-14 | 2019-01-10 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 xia 억제제로서의 치환된 테트라히드로이소퀴놀린 화합물 |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| HUE032622T2 (en) | 2012-08-03 | 2017-10-30 | Bristol Myers Squibb Co | Dihydropyridone P1 as factor XIA inhibitors |
| KR20150038369A (ko) * | 2012-08-03 | 2015-04-08 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 XIa 억제제로서의 디히드로피리돈 P1 |
| WO2014059202A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2906551B1 (en) | 2012-10-12 | 2018-02-28 | Bristol-Myers Squibb Company | Crystalline forms of a factor xia inhibitor |
| WO2014059214A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| JP6479763B2 (ja) | 2013-03-25 | 2019-03-06 | 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アゾール含有のテトラヒドロイソキノリン |
| EP2978425B1 (en) | 2013-03-27 | 2017-09-27 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| FR3010076B1 (fr) * | 2013-09-02 | 2016-12-23 | Centre Nat De La Rech Scient - Cnrs - | Inhibiteurs de metalloproteases, leurs procedes de preparation et leurs utilisations therapeutiques |
| NO2760821T3 (es) | 2014-01-31 | 2018-03-10 | ||
| US20170002006A1 (en) * | 2014-01-31 | 2017-01-05 | Bristol-Myers Squibb Company | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
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| ES2714283T3 (es) * | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
| NO2721243T3 (es) * | 2014-10-01 | 2018-10-20 | ||
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| US10160750B2 (en) | 2015-06-19 | 2018-12-25 | Bristol-Myers Squibb Company | Diamide macrocycles as factor XIa inhibitors |
| US10676477B2 (en) | 2015-07-29 | 2020-06-09 | Bristol-Myers Squibb Company | Factor XIa macrocycle inhibitors bearing a non-aromatic P2' group |
| EP3328851B1 (en) | 2015-07-29 | 2020-04-22 | Bristol-Myers Squibb Company | Factor xia macrocyclic inhibitors bearing alkyl or cycloalkyl p2' moieties |
| SG10202003705WA (en) | 2015-10-01 | 2020-06-29 | Biocryst Pharm Inc | Human plasma kallikrein inhibitors |
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| EP3423458A1 (en) | 2016-03-02 | 2019-01-09 | Bristol-Myers Squibb Company | Diamide macrocycles having factor xia inhibiting activity |
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| EP4146205A4 (en) | 2020-05-05 | 2024-05-29 | Nuvalent, Inc. | HETEROAROMATIC MACROCYCLIC ETHER-BASED CHEMOTHERAPY AGENTS |
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| WO2007070818A1 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| US8466295B2 (en) | 2005-12-14 | 2013-06-18 | Bristol-Myers Squibb Company | Thiophene derivatives as factor XIa inhibitors |
| PE20071132A1 (es) * | 2005-12-23 | 2007-12-14 | Bristol Myers Squibb Co | Compuestos macrociclicos como inhibidores del factor viia |
| US20080099168A1 (en) | 2006-10-26 | 2008-05-01 | Kou-Chang Liu | Soft and absorbent tissue products |
| US8410155B2 (en) | 2006-12-15 | 2013-04-02 | 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 |
| JP5537442B2 (ja) | 2008-03-13 | 2014-07-02 | ブリストル−マイヤーズ スクイブ カンパニー | 第ｘｉａ因子阻害剤としてのピリダジン誘導体 |
| EP3786165A1 (en) | 2010-02-11 | 2021-03-03 | Bristol-Myers Squibb Company | Synthetic intermediates for producing 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 |
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| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| KR101937514B1 (ko) | 2011-10-14 | 2019-01-10 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 xia 억제제로서의 치환된 테트라히드로이소퀴놀린 화합물 |
| ES2572908T3 (es) | 2011-10-14 | 2016-06-03 | Bristol-Myers Squibb Company | Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa |
| KR20150038369A (ko) | 2012-08-03 | 2015-04-08 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 XIa 억제제로서의 디히드로피리돈 P1 |
| HUE032622T2 (en) | 2012-08-03 | 2017-10-30 | Bristol Myers Squibb Co | Dihydropyridone P1 as factor XIA inhibitors |
| WO2014059202A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| WO2014059214A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2906551B1 (en) | 2012-10-12 | 2018-02-28 | Bristol-Myers Squibb Company | Crystalline forms of a factor xia inhibitor |
-
2012
- 2012-08-03 TW TW101128173A patent/TW201311689A/zh unknown
- 2012-08-06 CN CN201280049108.9A patent/CN103857681B/zh active Active
- 2012-08-06 EP EP12762427.8A patent/EP2739628B1/en active Active
- 2012-08-06 HU HUE12762427A patent/HUE034487T2/en unknown
- 2012-08-06 RS RS20170852A patent/RS56244B1/sr unknown
- 2012-08-06 PL PL12762427T patent/PL2739628T3/pl unknown
- 2012-08-06 CA CA2844254A patent/CA2844254A1/en not_active Abandoned
- 2012-08-06 EA EA201490418A patent/EA024791B1/ru not_active IP Right Cessation
- 2012-08-06 US US14/236,973 patent/US9221818B2/en active Active
- 2012-08-06 WO PCT/US2012/049706 patent/WO2013022818A1/en active Application Filing
- 2012-08-06 SI SI201231004T patent/SI2739628T1/sl unknown
- 2012-08-06 MX MX2014000831A patent/MX345763B/es active IP Right Grant
- 2012-08-06 PT PT127624278T patent/PT2739628T/pt unknown
- 2012-08-06 BR BR112014002202A patent/BR112014002202A2/pt not_active Application Discontinuation
- 2012-08-06 JP JP2014524152A patent/JP6158181B2/ja active Active
- 2012-08-06 ES ES12762427.8T patent/ES2635088T3/es active Active
- 2012-08-06 DK DK12762427.8T patent/DK2739628T3/en active
- 2012-08-06 LT LTEP12762427.8T patent/LT2739628T/lt unknown
- 2012-08-07 AR ARP120102878A patent/AR088748A1/es unknown
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2015
- 2015-11-16 US US14/942,013 patent/US9611274B2/en active Active
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2017
- 2017-02-21 US US15/437,605 patent/US9902742B2/en active Active
- 2017-07-21 HR HRP20171122TT patent/HRP20171122T1/hr unknown
- 2017-09-04 CY CY20171100930T patent/CY1119281T1/el unknown
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- 2018-01-25 US US15/879,619 patent/US10208068B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| LT2739628T (lt) | 2017-08-25 |
| EA024791B1 (ru) | 2016-10-31 |
| CN103857681B (zh) | 2017-07-14 |
| CN103857681A (zh) | 2014-06-11 |
| PT2739628T (pt) | 2017-08-02 |
| US9611274B2 (en) | 2017-04-04 |
| US20140221338A1 (en) | 2014-08-07 |
| JP2014521701A (ja) | 2014-08-28 |
| US20180148461A1 (en) | 2018-05-31 |
| SI2739628T1 (sl) | 2017-08-31 |
| CY1119281T1 (el) | 2018-02-14 |
| WO2013022818A1 (en) | 2013-02-14 |
| ES2635088T3 (es) | 2017-10-02 |
| CA2844254A1 (en) | 2013-02-14 |
| MX345763B (es) | 2017-02-15 |
| DK2739628T3 (en) | 2017-09-11 |
| US10208068B2 (en) | 2019-02-19 |
| US9902742B2 (en) | 2018-02-27 |
| US20170158712A1 (en) | 2017-06-08 |
| EP2739628B1 (en) | 2017-06-07 |
| HRP20171122T1 (hr) | 2017-10-06 |
| BR112014002202A2 (pt) | 2017-03-07 |
| PL2739628T3 (pl) | 2017-11-30 |
| MX2014000831A (es) | 2014-02-27 |
| EA201490418A1 (ru) | 2014-05-30 |
| RS56244B1 (sr) | 2017-11-30 |
| US20160068544A1 (en) | 2016-03-10 |
| EP2739628A1 (en) | 2014-06-11 |
| HUE034487T2 (en) | 2018-02-28 |
| JP6158181B2 (ja) | 2017-07-05 |
| TW201311689A (zh) | 2013-03-16 |
| US9221818B2 (en) | 2015-12-29 |
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