GEP20186892B - 2-amino-3, 5, 5-trifluoro-3, 4, 5, 6-tetrahydropyridines as bace1 inhibitors for treatment of alzheimer's disease - Google Patents
2-amino-3, 5, 5-trifluoro-3, 4, 5, 6-tetrahydropyridines as bace1 inhibitors for treatment of alzheimer's diseaseInfo
- Publication number
- GEP20186892B GEP20186892B GEAP201514248A GEAP2015014248A GEP20186892B GE P20186892 B GEP20186892 B GE P20186892B GE AP201514248 A GEAP201514248 A GE AP201514248A GE AP2015014248 A GEAP2015014248 A GE AP2015014248A GE P20186892 B GEP20186892 B GE P20186892B
- Authority
- GE
- Georgia
- Prior art keywords
- alzheimer
- treatment
- tetrahydropyridines
- trifluoro
- disease
- Prior art date
Links
- 208000024827 Alzheimer disease Diseases 0.000 title abstract 2
- BFTKEARFXHXNIW-UHFFFAOYSA-N 3,3,5-trifluoro-4,5-dihydro-2H-pyridin-6-amine Chemical class NC1=NCC(CC1F)(F)F BFTKEARFXHXNIW-UHFFFAOYSA-N 0.000 title 1
- 229940125759 BACE1 protease inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
-
- 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
-
- 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
-
- 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
- C07D227/00—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00
- C07D227/02—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D227/06—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D227/10—Nitrogen atoms not forming part of a nitro radical
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA201400086 | 2014-02-19 | ||
| DKPA201400349 | 2014-07-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GEP20186892B true GEP20186892B (en) | 2018-09-10 |
Family
ID=59009438
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GEAP201514248A GEP20186892B (en) | 2014-02-19 | 2015-02-17 | 2-amino-3, 5, 5-trifluoro-3, 4, 5, 6-tetrahydropyridines as bace1 inhibitors for treatment of alzheimer's disease |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US20170066741A1 (enExample) |
| EP (1) | EP3107897A1 (enExample) |
| JP (1) | JP6483146B2 (enExample) |
| KR (1) | KR20160115936A (enExample) |
| CN (1) | CN106029639B (enExample) |
| AP (1) | AP2016009370A0 (enExample) |
| AR (1) | AR099489A1 (enExample) |
| AU (1) | AU2015220873A1 (enExample) |
| CA (1) | CA2940028A1 (enExample) |
| CL (1) | CL2016002072A1 (enExample) |
| CR (1) | CR20160352A (enExample) |
| DO (1) | DOP2016000194A (enExample) |
| EA (1) | EA031132B1 (enExample) |
| EC (1) | ECSP16072941A (enExample) |
| GE (1) | GEP20186892B (enExample) |
| IL (1) | IL246875A0 (enExample) |
| MA (1) | MA39225A1 (enExample) |
| MX (1) | MX2016010777A (enExample) |
| PE (1) | PE20161225A1 (enExample) |
| PH (1) | PH12016501600A1 (enExample) |
| RU (1) | RU2016133626A (enExample) |
| SG (1) | SG11201606812WA (enExample) |
| TW (1) | TW201609700A (enExample) |
| UA (1) | UA117695C2 (enExample) |
| WO (1) | WO2015124576A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106029639B (zh) | 2014-02-19 | 2019-01-08 | H.隆德贝克有限公司 | 治疗阿尔茨海默病的bace1抑制剂的2-氨基-3，5，5-三氟-3，4，5，6-四氢吡啶 |
| 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 |
| 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 |
| US10011596B2 (en) * | 2015-08-12 | 2018-07-03 | H. Lundbeck A/S | 2-amino-3-fluoro-3-(fluoromethyl)-6-methyl-6-phenyl-3,4,5,6-tetrahydropyridines as BACE1 inhibitors |
| WO2017044807A2 (en) | 2015-09-09 | 2017-03-16 | The Trustees Of Columbia University In The City Of New York | Reduction of er-mam-localized app-c99 and methods of treating alzheimer's disease |
| TW201726651A (zh) * | 2015-09-23 | 2017-08-01 | 健生藥品公司 | ２，３，４，５－四氫吡啶－６－胺衍生物 |
| US10034861B2 (en) | 2016-07-04 | 2018-07-31 | H. Lundbeck A/S | 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors |
| CA3041595A1 (en) | 2016-10-28 | 2018-05-03 | H. Lundbeck A/S | Combination treatments comprising administration of imidazopyrazinones |
| WO2018078038A1 (en) | 2016-10-28 | 2018-05-03 | H. Lundbeck A/S | Combination treatments comprising imidazopyrazinones for the treatment of psychiatric and/or cognitive disorders |
| WO2018114910A1 (en) | 2016-12-21 | 2018-06-28 | H. Lundbeck A/S | 6-amino-5-fluoro-5-(fluoromethyl)-2,3,4,5-tetrahydropyridin-2-yl-phenyl-5-(methoxy-d3)-pyrazine-2-carboxamides and fluorinated derivatives thereof as bace1 inhibitors |
| UY37918A (es) | 2017-10-05 | 2019-04-30 | Fulcrum Therapeutics Inc | Inhibidores de la quinasa p38 que reducen la expresión de dux4 y de los genes corriente abajo para el tratamiento de fshd |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| KR20200099154A (ko) | 2017-12-14 | 2020-08-21 | 하. 룬드벡 아크티에셀스카브 | 1H-피라졸로[4,3-b]피리딘의 투여를 포함하는 조합 치료제 |
| AR113926A1 (es) | 2017-12-14 | 2020-07-01 | H Lundbeck As | Derivados de 1h-pirazolo[4,3-b]piridinas |
| WO2019121840A1 (en) | 2017-12-20 | 2019-06-27 | H. Lundbeck A/S | Pyrazolo[3,4-b]pyridines and imidazo[1,5-b]pyridazines as pde1 inhibitors |
| KR102507861B1 (ko) | 2018-04-19 | 2023-03-09 | 삼성에스디에스 주식회사 | 부채널 공격에 안전한 연산 장치 및 방법 |
| KR102510077B1 (ko) | 2018-04-24 | 2023-03-14 | 삼성에스디에스 주식회사 | 부채널 공격에 안전한 연산 장치 및 방법 |
| US12042492B2 (en) | 2020-10-09 | 2024-07-23 | Texas Tech University System | BACE1 inhibitory ligand molecules against amyloid beta-induced synaptic and mitochondrial toxicities |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7067507B2 (en) * | 2001-06-12 | 2006-06-27 | Pharmacia & Upjohn Company | Macrocycles useful in the treatment of Alzheimer's disease |
| GB0124928D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| SI1474395T1 (sl) * | 2002-02-12 | 2008-02-29 | Smithkline Beecham Corp | Nikotinamidni derivati, uporabni kot inhibitorji p38 |
| TWI431004B (zh) * | 2008-05-02 | 2014-03-21 | Lilly Co Eli | Ｂａｃｅ抑制劑 |
| EP2580200B1 (en) * | 2010-06-09 | 2016-09-14 | Janssen Pharmaceutica, N.V. | 5,6-dihydro-2h-[1,4]oxazin-3-yl-amine derivatives useful as inhibitors of beta-secretase (bace) |
| CN103261199A (zh) * | 2010-10-29 | 2013-08-21 | 盐野义制药株式会社 | 萘啶衍生物 |
| CA2824097A1 (en) * | 2011-01-12 | 2012-07-19 | Novartis Ag | Oxazine derivatives and their use in the treatment of neurological disorders |
| MA34898B1 (fr) * | 2011-01-13 | 2014-02-01 | Novartis Ag | Nouveaux dérivés hétérocycliques et leur utilisation dans le traitement de troubles neurologiques |
| US8754075B2 (en) * | 2011-04-11 | 2014-06-17 | Hoffmann-La Roche Inc. | 1,3-oxazines as BACE1 and/or BACE2 inhibitors |
| WO2012147763A1 (ja) * | 2011-04-26 | 2012-11-01 | 塩野義製薬株式会社 | オキサジン誘導体およびそれを含有するｂａｃｅ１阻害剤 |
| WO2012168164A1 (en) * | 2011-06-07 | 2012-12-13 | F. Hoffmann-La Roche Ag | Halogen-alkyl-1,3 oxazines as bace1 and/or bace2 inhibitors |
| 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 |
| WO2013142613A1 (en) | 2012-03-20 | 2013-09-26 | Elan Pharmaceuticals, Inc. | Spirocyclic dihydro-thiazine and dihydro-oxazine bace inhibitors, 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 |
| EP2912035A4 (en) | 2012-10-24 | 2016-06-15 | Shionogi & Co | DERIVATIVES OF DIHYDROOXAZINE OR OXAZEPINE HAVING BACE1 INHIBITING ACTIVITY |
| AU2014223334C1 (en) | 2013-03-01 | 2018-10-18 | Amgen Inc. | Perfluorinated 5,6-dihydro-4H-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| CN106029639B (zh) | 2014-02-19 | 2019-01-08 | H.隆德贝克有限公司 | 治疗阿尔茨海默病的bace1抑制剂的2-氨基-3，5，5-三氟-3，4，5，6-四氢吡啶 |
| 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 |
-
2015
- 2015-02-17 CN CN201580009034.XA patent/CN106029639B/zh not_active Expired - Fee Related
- 2015-02-17 US US15/119,639 patent/US20170066741A1/en not_active Abandoned
- 2015-02-17 KR KR1020167021930A patent/KR20160115936A/ko not_active Withdrawn
- 2015-02-17 SG SG11201606812WA patent/SG11201606812WA/en unknown
- 2015-02-17 JP JP2016551851A patent/JP6483146B2/ja not_active Expired - Fee Related
- 2015-02-17 TW TW104105281A patent/TW201609700A/zh unknown
- 2015-02-17 MA MA39225A patent/MA39225A1/fr unknown
- 2015-02-17 GE GEAP201514248A patent/GEP20186892B/en unknown
- 2015-02-17 MX MX2016010777A patent/MX2016010777A/es unknown
- 2015-02-17 AU AU2015220873A patent/AU2015220873A1/en not_active Abandoned
- 2015-02-17 PE PE2016001299A patent/PE20161225A1/es not_active Application Discontinuation
- 2015-02-17 RU RU2016133626A patent/RU2016133626A/ru not_active Application Discontinuation
- 2015-02-17 CA CA2940028A patent/CA2940028A1/en not_active Abandoned
- 2015-02-17 CR CR20160352A patent/CR20160352A/es unknown
- 2015-02-17 AP AP2016009370A patent/AP2016009370A0/en unknown
- 2015-02-17 WO PCT/EP2015/053327 patent/WO2015124576A1/en not_active Ceased
- 2015-02-17 EA EA201691447A patent/EA031132B1/ru not_active IP Right Cessation
- 2015-02-17 EP EP15707304.0A patent/EP3107897A1/en not_active Withdrawn
- 2015-02-17 UA UAA201608414A patent/UA117695C2/uk unknown
- 2015-02-18 AR ARP150100475A patent/AR099489A1/es unknown
- 2015-02-19 US US14/625,658 patent/US9353084B2/en not_active Expired - Fee Related
-
2016
- 2016-07-21 IL IL246875A patent/IL246875A0/en unknown
- 2016-07-28 DO DO2016000194A patent/DOP2016000194A/es unknown
- 2016-08-11 PH PH12016501600A patent/PH12016501600A1/en unknown
- 2016-08-17 CL CL2016002072A patent/CL2016002072A1/es unknown
- 2016-09-09 EC ECIEPI201672941A patent/ECSP16072941A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EA201691447A1 (ru) | 2016-12-30 |
| DOP2016000194A (es) | 2016-09-30 |
| KR20160115936A (ko) | 2016-10-06 |
| TW201609700A (zh) | 2016-03-16 |
| CL2016002072A1 (es) | 2017-01-20 |
| EP3107897A1 (en) | 2016-12-28 |
| UA117695C2 (uk) | 2018-09-10 |
| AR099489A1 (es) | 2016-07-27 |
| MA39225A1 (fr) | 2017-04-28 |
| US9353084B2 (en) | 2016-05-31 |
| CN106029639A (zh) | 2016-10-12 |
| AU2015220873A1 (en) | 2016-08-11 |
| RU2016133626A (ru) | 2018-03-20 |
| AP2016009370A0 (en) | 2016-08-31 |
| MX2016010777A (es) | 2016-10-26 |
| PE20161225A1 (es) | 2016-12-04 |
| CR20160352A (es) | 2016-10-20 |
| CA2940028A1 (en) | 2015-08-27 |
| RU2016133626A3 (enExample) | 2018-09-25 |
| ECSP16072941A (es) | 2017-02-24 |
| JP6483146B2 (ja) | 2019-03-13 |
| US20150232449A1 (en) | 2015-08-20 |
| CN106029639B (zh) | 2019-01-08 |
| SG11201606812WA (en) | 2016-09-29 |
| US20170066741A1 (en) | 2017-03-09 |
| EA031132B1 (ru) | 2018-11-30 |
| IL246875A0 (en) | 2016-08-31 |
| PH12016501600A1 (en) | 2017-02-06 |
| JP2017506237A (ja) | 2017-03-02 |
| WO2015124576A1 (en) | 2015-08-27 |
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