HRP20210211T1 - Triazoli namijenjeni reguliranju homeostaze unutarstaničnog kalcija - Google Patents
Triazoli namijenjeni reguliranju homeostaze unutarstaničnog kalcija Download PDFInfo
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- HRP20210211T1 HRP20210211T1 HRP20210211TT HRP20210211T HRP20210211T1 HR P20210211 T1 HRP20210211 T1 HR P20210211T1 HR P20210211T T HRP20210211T T HR P20210211TT HR P20210211 T HRP20210211 T HR P20210211T HR P20210211 T1 HRP20210211 T1 HR P20210211T1
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4192—1,2,3-Triazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
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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
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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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0029—Parenteral nutrition; Parenteral nutrition compositions as drug carriers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (15)
1. Spoj formule (I):
[image]
,
naznačen time što
R1 je C1-4 alkilenski biradikal, koji može biti supstituiran s jednim ili više supstituenata, koje se neovisno bira iz skupine koju čine C1-4 alkil, C6-10 aril, F, Cl, CN i NO2;
R2 je C1-4 alkilenski biradikal, koji može biti supstituiran s jednim ili dva supstituenta, koje se neovisno bira iz skupine koju čine metil, etil, propil, izopropil, alil, propargil, butil, izobutil, sec-butil, tert-butil, hidroksimetil, 1-hidroksietil, 2-hidroksietil, 3-aminopropil, 4-aminobutil, 3-gvanidilpropil, 3-indolilmetil, penil, 1-naftil, 2-naftil, benzil, 4-hidroksibenzil, C6-10 heteroaril;
R3 je H;
m se bira između 0, 1, 2 i 4;
n se bira između 0, 1 i 2;
X se neovisno bira iz skupine koju čine OH, O(C1-4 alkil), O(C6-10 aril), OCF3, S(C1-4 alkil), S(C6-10 aril), C1-6 alkil, CF3, NHC(O)(C1-4 alkil) i halogen; ili dvije skupine X mogu predstavljati biradikal metilendioksi, etilendioksi ili propilendioksi; i
Y se bira iz skupine koju čine -CO2H, -CO2(C1-4 alkil), -N(C1-4 alkil)2, ili njegov farmaceutski prihvatljivi stereoizomer, sol, solvat ili kompleks.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je R1 -CH2-.
3. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je R2 biradikal -CH2- ili -CH2-CH2-, koji može biti supstituiran s jednim ili dva supstituenta, koje se neovisno bira iz skupine koju čine metil, izopropil, izobutil i benzil.
4. Spoj u skladu s patentnim zahtjevom 3, naznačen time što je R2 biradikal -CH2-, koji može biti supstituiran s dva metilna supstituenta ili s jednim supstituentom, kojeg se bira iz skupine koju čine izopropil, izobutil i benzil, ili što je R2 biradikal -CH2-CH2-.
5. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je m 1.
6. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je n 0.
7. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je X O(C1-4 alkil) ili halogen.
8. Spoj u skladu s patentnim zahtjevom 7, naznačen time što je X skupina metoksi na položaju meta ili para ili klor.
9. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što se Y bira iz skupine koju čine CO2H, CO2Me, -NMe2, -NEt2, ili farmaceutski prihvatljive soli navedenih skupina; po mogućnosti što se Y bira iz skupine koju čine CO2H i -NMe2.
10. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time što ga se bira iz skupine koju čine:
1-karboksimetil-4-[3-(metoksi)feniltiometil]-1H-1,2,3-triazol,
1-[2-(N,N-dimetilamino)etil]-4-[4-(metoksi)feniltiometil]-1H-1,2,3-triazol,
1-karboksimetil-4-[4-(metoksi)feniltiometil]-1H-1,2,3-triazol,
(S)-1-(1-karboksi-2-feniletil)-4-[3-(metoksi)feniltiometil]-1H-1,2,3-triazol,
(R)-1-(1-karboksi-2-feniletil)-4-[3-(metoksi)feniltiometil]-1H-1,2,3-triazol,
(S)-1-(1-karboksi-3-metilbutil)-4-[3-(metoksi)feniltiometil]-1H-1,2,3-triazol,
(R)-1-(1-karboksi-3-metilbutil)-4-[3-(metoksi)feniltiometil]-1H-1,2,3-triazol,
(S)-1-(1-karboksi-2-metilpropil)-4-[3-(metoksi)feniltiometil]-1H-1,2,3-triazol,
(R)-1-(1-karboksi-2-metilpropil)-4-[3-(metoksi)feniltiometil]-1H-1,2,3-triazol,
1-(1-karboksi-1-metiletil)-4-[3-(metoksi)feniltiometil]-1H-1,2,3-triazol,
1-metoksikarbonilmetil-4-(fenilsulfinilmetil)-1H-1,2,3-triazol, te
1-karboksimetil-4-[3-(metoksi)fenilsulfonilmetil]-1H-1,2,3-triazol,
1-karboksimetil-4-[3-(klor)feniltiometil]-1H-1,2,3-triazol,
ili njihove soli.
11. Farmaceutski pripravak, naznačen time što sadrži spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1-10, te jedno ili više farmaceutski prihvatljivih pomoćnih sredstava ili vehikuluma.
12. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačen time što je namijenjen upotrebi kao medicinski proizvod.
13. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačen time što je namijenjen upotrebi u liječenju i/ili sprečavanje poremećaja i bolesti skeletnih mišića, poremećaja i bolesti srca, te poremećaja i bolesti živčanog sustava.
14. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 13, naznačen time što
poremećaje i bolesti skeletnih mišića se bira između mišićnih distrofija, prirođenih miopatija, metaboličkih miopatija, atrofije mišića i sarkopenije; gdje je po mogućnosti poremećaj ili bolest skeletnih mišića Duchennova mišićna distrofija ili Beckerova mišićna distrofija; ili
poremećaje i bolesti srca se bira između zatajenja srca, srčane ishemije, srčanih aritmija i kardiomiopatija; ili
poremećaje i bolesti živčanog sustava se bira između inzulta, Alzheimerove bolesti, frontotemporalne demencije i poremećaja kognitivnih funkcija.
15. Postupak sinteze spoja formule (I) u skladu s bilo kojim od patentnih zahtjeva 1-10, naznačen time što se sastoji u:
a) reakciji alkina formule (II)
[image]
s azidom formule (III)
N3-R2-Y (III),
izborno u prisutnosti bakrovog katalizatora, te izborno u prisutnosti baze kako bi se dobilo spoj formule (I),
gdje:
skupine R1, R2, R3, m, n i X u spojevima formula (II)-(III) su u skladu s bilo kojim od patentnih zahtjeva 1-10, a Y je skupina u skladu s bilo kojim od patentnih zahtjeva 1-10, koja može biti zaštićena zaštitnom skupinom za karboksil, zaštitnom skupinom za hidroksil ili zaštitnom skupinom za amino;
b) kada je n 0 u spoju formule (I) dobivenom u koraku a), izbornoj obradi navedenog spoja formule (I) oksidacijskim sredstvom kako bi se dobilo spoj formule (I), gdje je n 1 ili 2, R1, R2, R3, m i X su u skladu s bilo kojim od patentnih zahtjeva 1-10, a Y je skupina u skladu s bilo kojim od patentnih zahtjeva 1-10, koja može biti zaštićena zaštitnom skupinom za karboksil, zaštitnom skupinom za hidroksil ili zaštitnom skupinom za amino; i
c) kada spoj formule (I) dobiven u koraku a) ili b) ima skupinu Y zaštićenu zaštitnom skupinom, uklanjanju navedene zaštitne skupina kako bi se dobilo spoj formule (I), gdje su R1, R2, R3, m, n, X i Y u skladu s bilo kojim od patentnih zahtjeva 1-10.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES201630670A ES2643856B1 (es) | 2016-05-24 | 2016-05-24 | Triazoles para la regulación de la homeostasis de calcio intracelular |
| EP17735609.4A EP3466933B1 (en) | 2016-05-24 | 2017-05-23 | Triazoles for regulating intracellular calcium homeostasis |
| PCT/ES2017/070344 WO2017203083A1 (es) | 2016-05-24 | 2017-05-23 | Triazoles para la regulación de la homeostasis de calcio intracelular |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20210211T1 true HRP20210211T1 (hr) | 2021-03-19 |
Family
ID=59285262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20210211TT HRP20210211T1 (hr) | 2016-05-24 | 2017-05-23 | Triazoli namijenjeni reguliranju homeostaze unutarstaničnog kalcija |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US11377427B2 (hr) |
| EP (1) | EP3466933B1 (hr) |
| JP (1) | JP6983875B2 (hr) |
| CN (1) | CN109563056B (hr) |
| AU (1) | AU2017270485B2 (hr) |
| CA (1) | CA3025436C (hr) |
| CL (1) | CL2018003318A1 (hr) |
| DK (1) | DK3466933T3 (hr) |
| ES (2) | ES2643856B1 (hr) |
| HR (1) | HRP20210211T1 (hr) |
| HU (1) | HUE053371T2 (hr) |
| IL (1) | IL263168B2 (hr) |
| MX (1) | MX381545B (hr) |
| PL (1) | PL3466933T3 (hr) |
| PT (1) | PT3466933T (hr) |
| RU (1) | RU2753509C2 (hr) |
| WO (1) | WO2017203083A1 (hr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI759301B (zh) | 2016-05-24 | 2022-04-01 | 美商安美基公司 | 聚乙二醇化卡非佐米化合物 |
| EP4104835A4 (en) * | 2020-02-10 | 2024-05-01 | Juntendo Educational Foundation | INHIBITOR OF RYANODINE TYPE 2 RECEPTOR ACTIVITY |
| AU2023288798A1 (en) * | 2022-06-23 | 2025-01-09 | Administración General De La Comunidad Autónoma De Euskadi | Triazoles for use in the treatment of ocular diseases |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2703408B2 (ja) | 1990-12-28 | 1998-01-26 | 麒麟麦酒株式会社 | １，４‐ベンゾチアゼピン誘導体 |
| US6709599B1 (en) * | 1999-10-27 | 2004-03-23 | Rwe Nukem Corporation | Waste water treatment system with slip stream |
| US20040229781A1 (en) | 2000-05-10 | 2004-11-18 | Marks Andrew Robert | Compounds and methods for treating and preventing exercise-induced cardiac arrhythmias |
| US8022058B2 (en) | 2000-05-10 | 2011-09-20 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| CN1997633A (zh) * | 2004-05-25 | 2007-07-11 | 麦它波莱克斯股份有限公司 | 作为ppar调节剂的取代的三唑及其制备方法 |
| EP1802612A1 (en) * | 2004-10-12 | 2007-07-04 | Amgen, Inc | Novel b1 bradykinin receptor antagonists |
| US7515666B2 (en) | 2005-07-29 | 2009-04-07 | International Business Machines Corporation | Method for dynamically changing the frequency of clock signals |
| US7704990B2 (en) * | 2005-08-25 | 2010-04-27 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US8802726B2 (en) | 2006-02-03 | 2014-08-12 | Nicox S.A. | Use of nitrooxyderivative of drug for the treatment of muscular dystrophies |
| PT1986633E (pt) | 2006-02-10 | 2014-11-05 | Summit Corp Plc | Tratamento da distrofia muscular de duchenne |
| WO2007144785A2 (en) * | 2006-03-26 | 2007-12-21 | Uti Limited Partnership | Ryanodine receptor inhibitors and methods relating thereto |
| WO2008060332A2 (en) | 2006-06-02 | 2008-05-22 | The Trustees Of Columbia University In The City Of New York | Methods for treating or reducing muscle fatigue |
| WO2008144483A2 (en) | 2007-05-18 | 2008-11-27 | Armgo Pharma, Inc. | Agents for treating disorders involving modulation of ryanodine receptors |
| GB0715087D0 (en) | 2007-08-03 | 2007-09-12 | Summit Corp Plc | Drug combinations for the treatment of duchenne muscular dystrophy |
| GB0821307D0 (en) | 2008-11-21 | 2008-12-31 | Summit Corp Plc | Compounds for treatment of duchenne muscular dystrophy |
| WO2012019071A1 (en) | 2010-08-06 | 2012-02-09 | The Trustees Of Columbia University In The City Of New York | Methods of preventing and treating sarcopenia |
| WO2012037105A1 (en) | 2010-09-14 | 2012-03-22 | The Trustees Of Columbia University In The City Of New York | Methods of treating, ameliorating or preventing stress-induced neuronal disorders and diseases |
| WO2013085890A1 (en) | 2011-12-06 | 2013-06-13 | Glaxo Group Limited | Therapeutic methods |
| EP2828249B1 (en) * | 2012-03-23 | 2018-10-10 | The Regents of The University of California | Premature-termination-codons readthrough compounds |
| EP2708535A1 (en) * | 2012-05-11 | 2014-03-19 | Les Laboratoires Servier | Agents for treating disorders involving modulation of ryanodine receptors |
| US20160244435A1 (en) * | 2013-06-21 | 2016-08-25 | The Scripps Research Institute | Expanded therapeutic potential in nitroheteroaryl antimicrobials |
| EP2857388A1 (de) * | 2013-10-01 | 2015-04-08 | Grünenthal GmbH | Sulfon-haltige Azole |
| BR112016009214A8 (pt) | 2013-10-25 | 2020-03-24 | Jagerschmidt Catherine | uso de um composto para preparação de um medicamento para o tratamento de distrofia muscular e composição farmacêutica |
| EP3083587B1 (en) | 2013-12-16 | 2018-04-04 | Cadila Healthcare Limited | Oximino derivatives for the treatment of dyslipidemia |
| WO2016057656A1 (en) * | 2014-10-08 | 2016-04-14 | Mitobridge, Inc. | Ppar-delta agonists for use for treating mitochondrial, vascular, muscular, and demyelinating diseases |
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2016
- 2016-05-24 ES ES201630670A patent/ES2643856B1/es active Active
-
2017
- 2017-05-23 US US16/304,041 patent/US11377427B2/en active Active
- 2017-05-23 IL IL263168A patent/IL263168B2/en unknown
- 2017-05-23 ES ES17735609T patent/ES2853701T3/es active Active
- 2017-05-23 HU HUE17735609A patent/HUE053371T2/hu unknown
- 2017-05-23 CN CN201780045689.1A patent/CN109563056B/zh active Active
- 2017-05-23 RU RU2018141584A patent/RU2753509C2/ru active
- 2017-05-23 PL PL17735609T patent/PL3466933T3/pl unknown
- 2017-05-23 AU AU2017270485A patent/AU2017270485B2/en active Active
- 2017-05-23 CA CA3025436A patent/CA3025436C/en active Active
- 2017-05-23 WO PCT/ES2017/070344 patent/WO2017203083A1/es active Search and Examination
- 2017-05-23 PT PT177356094T patent/PT3466933T/pt unknown
- 2017-05-23 MX MX2018014414A patent/MX381545B/es unknown
- 2017-05-23 EP EP17735609.4A patent/EP3466933B1/en active Active
- 2017-05-23 HR HRP20210211TT patent/HRP20210211T1/hr unknown
- 2017-05-23 JP JP2019514862A patent/JP6983875B2/ja active Active
- 2017-05-23 DK DK17735609.4T patent/DK3466933T3/da active
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Also Published As
| Publication number | Publication date |
|---|---|
| RU2753509C2 (ru) | 2021-08-17 |
| ES2643856B1 (es) | 2018-08-03 |
| EP3466933A1 (en) | 2019-04-10 |
| EP3466933B1 (en) | 2020-12-02 |
| CN109563056B (zh) | 2022-08-16 |
| US20200317625A1 (en) | 2020-10-08 |
| ES2643856A1 (es) | 2017-11-24 |
| MX381545B (es) | 2025-03-12 |
| RU2018141584A3 (hr) | 2020-07-27 |
| JP6983875B2 (ja) | 2021-12-17 |
| AU2017270485A1 (en) | 2018-12-13 |
| AU2017270485B2 (en) | 2021-02-25 |
| PL3466933T3 (pl) | 2021-06-14 |
| CA3025436C (en) | 2024-02-20 |
| PT3466933T (pt) | 2021-02-23 |
| WO2017203083A1 (es) | 2017-11-30 |
| CN109563056A (zh) | 2019-04-02 |
| CA3025436A1 (en) | 2017-11-30 |
| ES2853701T3 (es) | 2021-09-17 |
| HUE053371T2 (hu) | 2021-06-28 |
| IL263168B2 (en) | 2023-09-01 |
| IL263168B1 (en) | 2023-05-01 |
| MX2018014414A (es) | 2019-04-22 |
| JP2019520423A (ja) | 2019-07-18 |
| IL263168A (en) | 2018-12-31 |
| RU2018141584A (ru) | 2020-06-25 |
| US11377427B2 (en) | 2022-07-05 |
| CL2018003318A1 (es) | 2019-04-12 |
| DK3466933T3 (da) | 2021-01-11 |
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