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AR110498A1 - DERIVADOS DE ISOXAZOLIL ÉTER COMO MODULADORES ALOSTÉRICOS POSITIVOS (PAM) DE RECEPTORES DE GABAA a5 - Google Patents

DERIVADOS DE ISOXAZOLIL ÉTER COMO MODULADORES ALOSTÉRICOS POSITIVOS (PAM) DE RECEPTORES DE GABAA a5

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Publication number
AR110498A1
AR110498A1 ARP170103429A ARP170103429A AR110498A1 AR 110498 A1 AR110498 A1 AR 110498A1 AR P170103429 A ARP170103429 A AR P170103429A AR P170103429 A ARP170103429 A AR P170103429A AR 110498 A1 AR110498 A1 AR 110498A1
Authority
AR
Argentina
Prior art keywords
alkyl
cycloalkyl
alkoxy
iii
halo
Prior art date
Application number
ARP170103429A
Other languages
English (en)
Inventor
Emmanuel Pinard
Henner Knust
Zbinden Katrin Groebke
Giuseppe Cecere
Andrew Thomas
Andreas Koblet
Maria Hernandez
- Fasching Bernhard Clemencia
Bernd Buettelman
Original Assignee
Hoffmann La Roche
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of AR110498A1 publication Critical patent/AR110498A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/501Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/10Spiro-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/06Peri-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/06Peri-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

Composiciones que incluye los compuestos y uso de los compuestos en el tratamiento de la enfermedad de Alzheimer. Reivindicación 1: Compuestos de fórmula (1) en donde X se selecciona de entre i) N, y ii) CH; Y se selecciona de entre i) N, y ii) CR¹⁰; Z se selecciona de entre i) N, y ii) CR¹¹; R¹ se selecciona de entre i) alquilo C₁₋₆, ii) halo-alquilo C₁₋₆, iii) alcoxi C₁₋₆, iv) halo-alcoxi C₁₋₆, v) hidroxi-alquilo C₁₋₆, vi) cicloalquilo C₃₋₈, vii) halógeno, y viii) amino sustituido en el átomo de nitrógeno con uno o dos sustituyentes seleccionados independientemente de entre a) H, b) alquilo C₁₋₆, y c) cicloalquilo C₃₋₈; R² se selecciona de entre i) H, y ii) halógeno; R³ se selecciona de entre i) H, ii) alquilo C₁₋₆, iii) cicloalquilo C₃₋₈, iv) hidroxi-alquilo C₁₋₆, y v) halo-alquilo C₁₋₆; R⁴ se selecciona de entre i) H, ii) alquilo C₁₋₆, iii) alcoxi C₁₋₆, iv) cicloalquilo C₃₋₈, y v) halógeno; R⁵ es H; R⁶ se selecciona de entre i) H, ii) alquilo C₁₋₆, iii) cicloalquilo C₃₋₈ sustituido con R⁷, R⁸ y R⁹, iv) cicloalquil C₃₋₈-alquilo C₁₋₆ sustituido con R⁷, R⁸ y R⁹, v) alquilsulfonil C₁₋₆-alquilo C₁₋₆, vi) ciano-alquilo C₁₋₆, vii) hidroxi-alquilo C₁₋₆, viii) dihidroxi-alquilo C₁₋₆, ix) halo-alquilo C₁₋₆, x) heterocicloalquilo sustituido con R⁷, R⁸ y R⁹, y xi) heterocicloalquil-alquilo C₁₋₆ sustituido con R⁷, R⁸ y R⁹; R⁷, R⁸ y R⁹ se seleccionan independientemente de entre i) H, ii) alquilo C₁₋₆, iii) alcoxi C₁₋₆, iv) alcoxialquilo C₁₋₆, v) alcoxicarbonilo C₁₋₆, vi) ciano, vii) cicloalcoxi C₃₋₈, viii) cicloalquilo C₃₋₈, ix) halo-alcoxi C₁₋₆, x) halo-alquilo C₁₋₆, xi) halógeno, xii) hidroxi, xiii) hidroxi-alquilo C₁₋₆, y xiv) oxo; R¹⁰ se selecciona de entre i) H, ii) alquilo C₁₋₆, iii) alcoxi C₁₋₆, iv) cicloalquilo C₃₋₈, y v) halógeno; R¹¹ se selecciona de entre i) H, ii) alquilo C₁₋₆, iii) alcoxi C₁₋₆, iv) cicloalquilo C₃₋₈, y v) halógeno; o R⁵ y R¹⁰ forman juntos -(CH₂)ₙ-; o R⁵ y R¹¹ forman juntos -(CH₂)ₙ-; o R⁵ y R⁶ junto con el átomo de nitrógeno al que están unidos forman un heterocicloalquilo sustituido con R⁷, R⁸ y R⁹; n se selecciona de entre 1 y 2; o sales farmacéuticamente aceptables.
ARP170103429A 2016-12-08 2017-12-07 DERIVADOS DE ISOXAZOLIL ÉTER COMO MODULADORES ALOSTÉRICOS POSITIVOS (PAM) DE RECEPTORES DE GABAA a5 AR110498A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP16202889 2016-12-08

Publications (1)

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AR110498A1 true AR110498A1 (es) 2019-04-03

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ARP170103429A AR110498A1 (es) 2016-12-08 2017-12-07 DERIVADOS DE ISOXAZOLIL ÉTER COMO MODULADORES ALOSTÉRICOS POSITIVOS (PAM) DE RECEPTORES DE GABAA a5

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US (3) US11091471B2 (es)
EP (1) EP3551627B1 (es)
JP (1) JP7084405B2 (es)
KR (1) KR102564643B1 (es)
CN (2) CN109923113B (es)
AR (1) AR110498A1 (es)
AU (1) AU2017373734B2 (es)
BR (1) BR112019006571A2 (es)
CA (1) CA3040024A1 (es)
CL (1) CL2019001458A1 (es)
CO (1) CO2019002692A2 (es)
CR (1) CR20190268A (es)
DK (1) DK3551627T3 (es)
ES (1) ES2910110T3 (es)
HR (1) HRP20220468T1 (es)
HU (1) HUE058355T2 (es)
IL (1) IL267054B (es)
LT (1) LT3551627T (es)
MA (1) MA48594B1 (es)
MX (1) MX2019006696A (es)
PE (1) PE20191156A1 (es)
PH (1) PH12019500664B1 (es)
PL (1) PL3551627T3 (es)
PT (1) PT3551627T (es)
RS (1) RS63106B1 (es)
SI (1) SI3551627T1 (es)
TW (1) TWI642666B (es)
UA (1) UA125524C2 (es)
WO (1) WO2018104419A1 (es)
ZA (1) ZA201902225B (es)

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WO2018104419A1 (en) 2016-12-08 2018-06-14 F. Hoffmann-La Roche Ag New isoxazolyl ether derivatives as gaba a alpha5 pam
BR112020025355A2 (pt) 2018-06-13 2021-03-09 F. Hoffmann-La Roche Ag Derivados de éter de isoxazolila como gaba a alfa5 pam
BR102019014802A2 (pt) 2018-07-20 2020-02-04 Boehringer Ingelheim Int difluorometil-fenil triazóis
HU231223B1 (hu) * 2018-09-28 2022-01-28 Richter Gedeon Nyrt. GABAA A5 receptor modulátor hatású biciklusos vegyületek
TW202202495A (zh) * 2020-03-26 2022-01-16 匈牙利商羅特格登公司 作為gamma-胺基丁酸A受體次單元alpha 5受體調節劑之㖠啶及吡啶并〔3,4-c〕嗒𠯤衍生物
WO2021191837A1 (en) * 2020-03-26 2021-09-30 Richter Gedeon Nyrt. 1,3-dihydro-2h-pyrrolo[3,4-c]pyridine derivatives as gabaa α5 receptor modulators
US20240425491A1 (en) 2021-05-05 2024-12-26 University College Cardiff Consultants Limited Heteroaryl compounds useful in the treatment of cognitive disorders
HUP2100338A1 (hu) 2021-09-29 2023-04-28 Richter Gedeon Nyrt GABAA ALFA5 receptor modulátor hatású biciklusos aminszármazékok
IL316702A (en) 2022-06-20 2024-12-01 Hoffmann La Roche Crystalline forms of 6-((5-methyl-3-(6-methylpyridin-3-yl)isoxazol-4-yl)methoxy)-N-(tetrahydropyran-4-yl)pyridazine-3-carboxamide
WO2024088928A1 (en) 2022-10-25 2024-05-02 F. Hoffmann-La Roche Ag Process for manufacturing alogabat
WO2024223450A1 (en) 2023-04-24 2024-10-31 F. Hoffmann-La Roche Ag Tablet comprising 6-((5-methyl-3-(6-methylpyridin-3-yl)isoxazol-4-yl)methoxy)- n-(tetrahydrapyran-4-yl)pyridazine-3-carboxamide
CN119080754A (zh) * 2023-06-05 2024-12-06 武汉人福创新药物研发中心有限公司 作为α5-GABAA受体调节剂的杂环化合物及其用途

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CA2682301A1 (en) 2007-04-18 2008-10-30 Astrazeneca Ab Xanthine compounds having a positive allosteric gabab receptor modulator effect
RS54355B1 (en) 2007-12-04 2016-04-28 F. Hoffmann-La Roche Ag. Isoxazole-pyridine derivatives
US7943619B2 (en) * 2007-12-04 2011-05-17 Hoffmann-La Roche Inc. Isoxazolo-pyridazine derivatives
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JP6012735B2 (ja) * 2011-09-15 2016-10-25 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft 新規ジヒドロキノリン−2−オン誘導体
KR20180037265A (ko) 2015-08-17 2018-04-11 루핀 리미티드 Parp 억제제로서의 헤테로아릴 유도체
ES2963759T3 (es) 2016-01-08 2024-04-01 Arcus Biosciences Inc Moduladores de la 5'-nucleotidasa, ecto y su uso
BR112018013761A2 (pt) 2016-01-08 2018-12-11 Celgene Corp compostos antiproliferativos e suas composições farmacêuticas e usos
WO2018104419A1 (en) 2016-12-08 2018-06-14 F. Hoffmann-La Roche Ag New isoxazolyl ether derivatives as gaba a alpha5 pam

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US20240279218A1 (en) 2024-08-22
CL2019001458A1 (es) 2019-10-18
JP7084405B2 (ja) 2022-06-14
RU2019118253A (ru) 2021-01-11
EP3551627B1 (en) 2022-02-16
KR20190088485A (ko) 2019-07-26
SI3551627T1 (sl) 2022-05-31
MX2019006696A (es) 2019-08-21
BR112019006571A2 (pt) 2019-07-02
MA48594A (fr) 2021-04-28
AU2017373734B2 (en) 2022-02-17
LT3551627T (lt) 2022-04-25
PE20191156A1 (es) 2019-09-09
PH12019500664B1 (en) 2023-08-11
HRP20220468T1 (hr) 2022-05-27
PL3551627T3 (pl) 2022-05-16
HUE058355T2 (hu) 2022-07-28
US20220411415A1 (en) 2022-12-29
TW201827424A (zh) 2018-08-01
US11091471B2 (en) 2021-08-17
CO2019002692A2 (es) 2019-04-12
IL267054B (en) 2021-07-29
PH12019500664A1 (en) 2019-12-16
IL267054A (en) 2019-08-29
MA48594B1 (fr) 2022-05-31
UA125524C2 (uk) 2022-04-13
ZA201902225B (en) 2019-12-18
CA3040024A1 (en) 2018-06-14
CN117285525A (zh) 2023-12-26
AU2017373734A1 (en) 2019-04-11
RU2019118253A3 (es) 2021-04-07
TWI642666B (zh) 2018-12-01
KR102564643B1 (ko) 2023-08-08
US20190300516A1 (en) 2019-10-03
PT3551627T (pt) 2022-04-06
CN109923113A (zh) 2019-06-21
ES2910110T3 (es) 2022-05-11
DK3551627T3 (da) 2022-04-19
CN109923113B (zh) 2023-10-13
WO2018104419A1 (en) 2018-06-14
JP2020510621A (ja) 2020-04-09
RS63106B1 (sr) 2022-04-29
CR20190268A (es) 2019-07-11
EP3551627A1 (en) 2019-10-16

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