PE20170947A1 - 2-amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de bace1 - Google Patents
2-amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de bace1Info
- Publication number
- PE20170947A1 PE20170947A1 PE2017000827A PE2017000827A PE20170947A1 PE 20170947 A1 PE20170947 A1 PE 20170947A1 PE 2017000827 A PE2017000827 A PE 2017000827A PE 2017000827 A PE2017000827 A PE 2017000827A PE 20170947 A1 PE20170947 A1 PE 20170947A1
- Authority
- PE
- Peru
- Prior art keywords
- difluoro
- phenyl
- amino
- tetrahydropyridines
- methyl
- Prior art date
Links
- 229940125759 BACE1 protease inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- 102100021257 Beta-secretase 1 Human genes 0.000 abstract 2
- 101710150192 Beta-secretase 1 Proteins 0.000 abstract 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- -1 2-amino-3,5-difluoro-6-methyl-6-phenyl-2,3,4,5-tetrahydropyridines Chemical class 0.000 abstract 1
- 208000024827 Alzheimer disease Diseases 0.000 abstract 1
- 208000037259 Amyloid Plaque Diseases 0.000 abstract 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 abstract 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 abstract 1
- 102000004190 Enzymes Human genes 0.000 abstract 1
- 108090000790 Enzymes Proteins 0.000 abstract 1
- XALHHBCHONQAFO-ZYSHUDEJSA-N NC=1[C@@](C[C@@H]([C@@](N=1)(C)C=1C=C(C=CC=1F)NC(C1=NC=C(C=C1)F)=O)F)(C)F Chemical compound NC=1[C@@](C[C@@H]([C@@](N=1)(C)C=1C=C(C=CC=1F)NC(C1=NC=C(C=C1)F)=O)F)(C)F XALHHBCHONQAFO-ZYSHUDEJSA-N 0.000 abstract 1
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 125000003709 fluoroalkyl group Chemical group 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/435—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
-
- 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
- A61P25/28—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Se refiere a compuestos derivados de 2-amino-3,5-difluoro-6-metil-6-fenil-2,3,4,5-tetrahidropiridinas de formula (I) en donde Ar es fenilo, piridilo, entre otros; R1 es uno o mas H, halogeno, fluoroalquilo C1-C3 o alquilo C1-C3. Es un compuesto seleccionado N-(3-((2R, 3S, 5S)-6-amino-3,5-difluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-fluoropicolinamida, entre otros. Tambien se refiere a una composicion farmaceutica que lo comprende. Dichos compuestos inhiben la enzima beta secretasa 1 (BACE1) siendo utiles en el tratamiento de trastornos para los cuales la reduccion de depositos de beta amiloides es beneficioso, tal como la enfermedad de Alzheimer
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA201400649 | 2014-11-10 | ||
| DKPA201500450 | 2015-08-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20170947A1 true PE20170947A1 (es) | 2017-07-13 |
Family
ID=54476983
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2017000827A PE20170947A1 (es) | 2014-11-10 | 2015-11-09 | 2-amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de bace1 |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US10059669B2 (es) |
| EP (1) | EP3218362B1 (es) |
| JP (1) | JP2017533253A (es) |
| KR (1) | KR20170082529A (es) |
| CN (1) | CN107074809A (es) |
| AU (1) | AU2015345257A1 (es) |
| BR (1) | BR112017009647A2 (es) |
| CA (1) | CA2964305A1 (es) |
| CL (1) | CL2017001113A1 (es) |
| CO (1) | CO2017004530A2 (es) |
| CR (1) | CR20170187A (es) |
| DO (1) | DOP2017000118A (es) |
| EA (1) | EA201790817A1 (es) |
| EC (1) | ECSP17028463A (es) |
| ES (1) | ES2710602T3 (es) |
| IL (1) | IL252091A0 (es) |
| MX (1) | MX2017006048A (es) |
| NI (1) | NI201700056A (es) |
| PE (1) | PE20170947A1 (es) |
| PH (1) | PH12017500829A1 (es) |
| RU (1) | RU2017116197A (es) |
| SG (1) | SG11201703177WA (es) |
| SV (1) | SV2017005434A (es) |
| TN (1) | TN2017000134A1 (es) |
| WO (1) | WO2016075062A1 (es) |
| ZA (1) | ZA201702799B (es) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CR20170187A (es) | 2014-11-10 | 2018-02-01 | H Lundbeck As | 2-Amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de BACE1 para el tratamiento de la enfermedad de Alzheimer |
| JO3458B1 (ar) | 2014-11-10 | 2020-07-05 | H Lundbeck As | 2- أمينو-6- (دايفلوروميثيل) – 5، 5- ديفلورو-6-فينيل-3،4، 5، 6-تيتراهيدروبيريدين كمثبطات bace1 |
| MA40941A (fr) | 2014-11-10 | 2017-09-19 | H Lundbeck As | 2-amino-5,5-difluoro-6-(fluorométhyl)-6-phényl-3,4,5,6-tétrahydropyridines comme inhibiteurs de bace1 |
| JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| TW201717948A (zh) | 2015-08-10 | 2017-06-01 | Ｈ 朗德貝克公司 | 包括給予２－胺基－３，５，５－三氟－３，４，５，６－四氫吡啶的聯合治療 |
| CA2993630A1 (en) | 2015-08-12 | 2017-02-16 | H. Lundbeck A/S | 2-amino-3-fluoro-3-(fluoromethyl)-6-methyl-6-phenyl-3,4,5,6-tetrahydropyridines as bace1 inhibitors |
| US10034861B2 (en) | 2016-07-04 | 2018-07-31 | H. Lundbeck A/S | 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors |
| CN106366073B (zh) * | 2016-10-24 | 2018-11-30 | 扬子江药业集团南京海陵药业有限公司 | 一种盐酸替吡嘧啶的制备方法 |
| HUE050403T2 (hu) | 2016-10-28 | 2020-12-28 | H Lundbeck As | Imidazopirazinonokkal végzett kombinációs kezelések pszichiátriai és/vagy kognitív betegségek kezelésére |
| WO2018078042A1 (en) | 2016-10-28 | 2018-05-03 | H. Lundbeck A/S | Combination treatments comprising administration of imidazopyrazinones |
| TW201829394A (zh) * | 2016-12-21 | 2018-08-16 | 丹麥商Ｈ 朗德貝克公司 | 作為ｂａｃｅ１抑制劑之６-胺基-５-氟-５-（氟甲基）-２，３，４，５-四氫吡啶-２-基-苯基-５-（甲氧基-ｄ）-吡-２-甲醯胺及其氟化衍生物 |
| AR113926A1 (es) | 2017-12-14 | 2020-07-01 | H Lundbeck As | Derivados de 1h-pirazolo[4,3-b]piridinas |
| HRP20211784T1 (hr) | 2017-12-14 | 2022-02-18 | H. Lundbeck A/S | Kombinacijski tretmani koji se sastoje od primjene 1h-pirazolo[4,3-b]piridina |
| CN117447475A (zh) | 2017-12-20 | 2024-01-26 | H.隆德贝克有限公司 | 作为PDE1抑制剂的吡唑并[4,3-b]吡啶和咪唑并[1,5-a]嘧啶 |
| CN109970681A (zh) * | 2019-04-19 | 2019-07-05 | 安徽海康药业有限责任公司 | 一种瑞格列奈的合成方法 |
| CN113720930A (zh) * | 2021-07-26 | 2021-11-30 | 南京一诺医药科技有限公司 | 一种hplc-ms/ms联用检测人血浆中奥美拉唑的方法 |
| CN114235985A (zh) * | 2021-11-25 | 2022-03-25 | 南京海纳医药科技股份有限公司 | 一种hplc-ms/ms联用检测人血浆中胍法辛的方法 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2450167A1 (en) | 2001-06-12 | 2002-12-19 | Elan Pharmaceuticals, Inc. | Macrocycles useful in the treatment of alzheimer's disease |
| GB0124928D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| ES2295553T3 (es) | 2002-02-12 | 2008-04-16 | Smithkline Beecham Corporation | Derivados de nicotinamida utiles como inhibidores de p38. |
| AR077277A1 (es) | 2009-07-09 | 2011-08-17 | Lilly Co Eli | Compuestos de biciclo (1,3)tiazin-2-amina formulacion farmaceutica que lo comprende y su uso para la manufactura de un medicamento util para el tratamiento de la enfermedad de alzheimer |
| EA021240B1 (ru) * | 2010-06-09 | 2015-05-29 | Янссен Фармацевтика Нв | Производные 5,6-дигидро-2h-[1,4]оксазин-3-иламина в качестве ингибиторов бета-секретазы (bace) |
| JP2014505688A (ja) | 2011-01-12 | 2014-03-06 | ノバルティス アーゲー | オキサジン誘導体および神経障害の処置におけるその使用 |
| CN106117193B (zh) | 2011-01-13 | 2019-09-13 | 诺华股份有限公司 | 新的杂环衍生物及其在神经性疾病治疗中的应用 |
| US8754075B2 (en) | 2011-04-11 | 2014-06-17 | Hoffmann-La Roche Inc. | 1,3-oxazines as BACE1 and/or BACE2 inhibitors |
| TW201247635A (en) | 2011-04-26 | 2012-12-01 | Shionogi & Co | Oxazine derivatives and a pharmaceutical composition for inhibiting BAC1 containing them |
| EA023261B1 (ru) | 2011-06-07 | 2016-05-31 | Ф.Хоффманн-Ля Рош Аг | Галоген-алкил-1,3-оксазины в качестве ингибиторов bace1 и(или) bace2 |
| UY34278A (es) | 2011-08-25 | 2013-04-05 | Novartis Ag | Derivados novedosos de oxazina y su uso en el tratamiento de enfermedades |
| US8338413B1 (en) | 2012-03-07 | 2012-12-25 | Novartis Ag | Oxazine derivatives and their use in the treatment of neurological disorders |
| EP2827857A4 (en) | 2012-03-20 | 2016-03-30 | Elan Pharm Inc | SPIROCYCLIC DIHYDRO-THIAZINE AND INHIBITORS OF BACE DIHYDRO-OXAZINE AND COMPOSITIONS AND USES THEREOF |
| WO2014056816A1 (en) | 2012-10-10 | 2014-04-17 | F. Hoffmann-La Roche Ag | COMBINATION OF AN Aβ ANTIBODY AND A BACE INHIBITOR |
| US9556135B2 (en) * | 2012-10-12 | 2017-01-31 | Amgen, Inc. | Amino-dihydrothiazine and amino-dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use |
| JP2016501827A (ja) | 2012-10-24 | 2016-01-21 | 塩野義製薬株式会社 | Ｂａｃｅ１阻害作用を有するジヒドロオキサジンまたはオキサゼピン誘導体 |
| CA2902212C (en) | 2013-03-01 | 2020-10-13 | Amgen Inc. | Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| JO3318B1 (ar) | 2013-06-18 | 2019-03-13 | Lilly Co Eli | مثبطات bace |
| AP2016009370A0 (en) | 2014-02-19 | 2016-08-31 | H Lundbeck As | 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahydropyridines as bace1 inhibitors for treatment of alzheimer's disease |
| TW201623295A (zh) | 2014-04-11 | 2016-07-01 | 塩野義製藥股份有限公司 | 具有ｂａｃｅ１抑制活性之二氫噻及二氫衍生物 |
| JO3458B1 (ar) | 2014-11-10 | 2020-07-05 | H Lundbeck As | 2- أمينو-6- (دايفلوروميثيل) – 5، 5- ديفلورو-6-فينيل-3،4، 5، 6-تيتراهيدروبيريدين كمثبطات bace1 |
| MA40941A (fr) | 2014-11-10 | 2017-09-19 | H Lundbeck As | 2-amino-5,5-difluoro-6-(fluorométhyl)-6-phényl-3,4,5,6-tétrahydropyridines comme inhibiteurs de bace1 |
| CR20170187A (es) | 2014-11-10 | 2018-02-01 | H Lundbeck As | 2-Amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de BACE1 para el tratamiento de la enfermedad de Alzheimer |
| TW201717948A (zh) | 2015-08-10 | 2017-06-01 | Ｈ 朗德貝克公司 | 包括給予２－胺基－３，５，５－三氟－３，４，５，６－四氫吡啶的聯合治療 |
| CA2993630A1 (en) | 2015-08-12 | 2017-02-16 | H. Lundbeck A/S | 2-amino-3-fluoro-3-(fluoromethyl)-6-methyl-6-phenyl-3,4,5,6-tetrahydropyridines as bace1 inhibitors |
-
2014
- 2014-11-09 CR CR20170187A patent/CR20170187A/es unknown
-
2015
- 2015-11-09 JP JP2017525124A patent/JP2017533253A/ja active Pending
- 2015-11-09 CA CA2964305A patent/CA2964305A1/en not_active Abandoned
- 2015-11-09 PE PE2017000827A patent/PE20170947A1/es unknown
- 2015-11-09 TN TN2017000134A patent/TN2017000134A1/en unknown
- 2015-11-09 AU AU2015345257A patent/AU2015345257A1/en not_active Abandoned
- 2015-11-09 BR BR112017009647A patent/BR112017009647A2/pt not_active Application Discontinuation
- 2015-11-09 KR KR1020177012461A patent/KR20170082529A/ko not_active Withdrawn
- 2015-11-09 EP EP15790975.5A patent/EP3218362B1/en active Active
- 2015-11-09 EA EA201790817A patent/EA201790817A1/ru unknown
- 2015-11-09 ES ES15790975T patent/ES2710602T3/es active Active
- 2015-11-09 SG SG11201703177WA patent/SG11201703177WA/en unknown
- 2015-11-09 MX MX2017006048A patent/MX2017006048A/es unknown
- 2015-11-09 US US15/524,479 patent/US10059669B2/en not_active Expired - Fee Related
- 2015-11-09 RU RU2017116197A patent/RU2017116197A/ru unknown
- 2015-11-09 WO PCT/EP2015/076014 patent/WO2016075062A1/en not_active Ceased
- 2015-11-09 CN CN201580060814.7A patent/CN107074809A/zh active Pending
-
2017
- 2017-04-20 ZA ZA2017/02799A patent/ZA201702799B/en unknown
- 2017-05-03 IL IL252091A patent/IL252091A0/en unknown
- 2017-05-04 CL CL2017001113A patent/CL2017001113A1/es unknown
- 2017-05-04 PH PH12017500829A patent/PH12017500829A1/en unknown
- 2017-05-05 CO CONC2017/0004530A patent/CO2017004530A2/es unknown
- 2017-05-09 EC ECIEPI201728463A patent/ECSP17028463A/es unknown
- 2017-05-09 SV SV2017005434A patent/SV2017005434A/es unknown
- 2017-05-09 DO DO2017000118A patent/DOP2017000118A/es unknown
- 2017-05-10 NI NI201700056A patent/NI201700056A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CR20170187A (es) | 2018-02-01 |
| KR20170082529A (ko) | 2017-07-14 |
| WO2016075062A1 (en) | 2016-05-19 |
| MX2017006048A (es) | 2017-06-19 |
| NI201700056A (es) | 2017-09-22 |
| JP2017533253A (ja) | 2017-11-09 |
| CO2017004530A2 (es) | 2017-07-28 |
| ES2710602T3 (es) | 2019-04-26 |
| US10059669B2 (en) | 2018-08-28 |
| ECSP17028463A (es) | 2017-08-31 |
| SG11201703177WA (en) | 2017-05-30 |
| IL252091A0 (en) | 2017-07-31 |
| PH12017500829A1 (en) | 2017-10-09 |
| TN2017000134A1 (en) | 2018-10-19 |
| RU2017116197A (ru) | 2018-12-13 |
| CN107074809A (zh) | 2017-08-18 |
| EA201790817A1 (ru) | 2017-09-29 |
| DOP2017000118A (es) | 2017-07-15 |
| CA2964305A1 (en) | 2016-05-19 |
| US20170313658A1 (en) | 2017-11-02 |
| BR112017009647A2 (pt) | 2017-12-19 |
| AU2015345257A1 (en) | 2017-05-04 |
| EP3218362B1 (en) | 2019-01-09 |
| ZA201702799B (en) | 2018-08-29 |
| EP3218362A1 (en) | 2017-09-20 |
| SV2017005434A (es) | 2017-07-19 |
| CL2017001113A1 (es) | 2017-12-01 |
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