DK3788043T3 - Spiropiperidin som allosteriske modulatorer af nicotinacetylcholinreceptorer - Google Patents

Spiropiperidin som allosteriske modulatorer af nicotinacetylcholinreceptorer Download PDF

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Publication number
DK3788043T3
DK3788043T3 DK19722488.4T DK19722488T DK3788043T3 DK 3788043 T3 DK3788043 T3 DK 3788043T3 DK 19722488 T DK19722488 T DK 19722488T DK 3788043 T3 DK3788043 T3 DK 3788043T3
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nicotinacetylcholine
spiropiperidine
receptors
allosteric modulators
allosteric
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DK19722488.4T
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English (en)
Inventor
Brendan M Crowley
Brian T Campbell
Harry R Chobanian
James I Fells
Deodial G Guiadeen
Thomas J Greshock
Kenneth J Leavitt
Vanessa L Rada
Ian M Bell
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Merck Sharp & Dohme Llc
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    • 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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • 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
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
    • 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
    • C07D413/08—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 carbon chain containing alicyclic rings
    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D417/08—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 carbon chain containing alicyclic 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
    • C07D417/14—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 three or more hetero rings
    • 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
    • C07D471/04—Ortho-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
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (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)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
DK19722488.4T 2018-05-01 2019-04-29 Spiropiperidin som allosteriske modulatorer af nicotinacetylcholinreceptorer DK3788043T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862665091P 2018-05-01 2018-05-01
PCT/US2019/029561 WO2019212927A1 (en) 2018-05-01 2019-04-29 Spiropiperidine allosteric modulators of nicotinic acetylcholine receptors

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DK3788043T3 true DK3788043T3 (da) 2024-12-16

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US (1) US11332463B2 (da)
EP (1) EP3788043B1 (da)
JP (1) JP7073533B2 (da)
KR (1) KR102587811B1 (da)
CN (1) CN112119076B (da)
AR (1) AR115065A1 (da)
AU (1) AU2019262917B2 (da)
BR (1) BR112020022088A8 (da)
CA (1) CA3098583C (da)
CL (2) CL2020002820A1 (da)
CO (1) CO2020013462A2 (da)
CR (1) CR20200509A (da)
DK (1) DK3788043T3 (da)
EA (1) EA202092608A1 (da)
EC (1) ECSP20067907A (da)
ES (1) ES2995040T3 (da)
FI (1) FI3788043T3 (da)
GE (2) GEP20227409B (da)
HR (1) HRP20241704T1 (da)
HU (1) HUE070339T2 (da)
IL (1) IL278154B2 (da)
JO (1) JOP20200272A1 (da)
LT (1) LT3788043T (da)
MA (1) MA52482B1 (da)
MD (1) MD3788043T2 (da)
MX (1) MX2020011489A (da)
MY (1) MY205690A (da)
NI (1) NI202000074A (da)
PE (1) PE20210052A1 (da)
PH (1) PH12020551779A1 (da)
PL (1) PL3788043T3 (da)
PT (1) PT3788043T (da)
RS (1) RS66290B1 (da)
SG (1) SG11202010459XA (da)
SI (1) SI3788043T1 (da)
TW (1) TWI839355B (da)
UA (1) UA126834C2 (da)
WO (1) WO2019212927A1 (da)
ZA (1) ZA202006507B (da)

Families Citing this family (5)

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Publication number Priority date Publication date Assignee Title
WO2018165520A1 (en) 2017-03-10 2018-09-13 Vps-3, Inc. Metalloenzyme inhibitor compounds
EP3962483A4 (en) * 2019-05-02 2023-01-25 Merck Sharp & Dohme LLC ALLOSTERIC SPIROPIPERIDINE MODULATORS OF NICOTINE ACETYLCHOLINE RECEPTORS
CN114727974A (zh) 2019-07-30 2022-07-08 艾科尼佐治疗股份有限公司 Hdac6抑制剂及其用途
WO2021091751A1 (en) * 2019-11-05 2021-05-14 Merck Sharp & Dohme Corp. Spiropiperidine allosteric modulators of nicotinic acetylcholine receptors
JP7648027B2 (ja) * 2019-12-19 2025-03-18 クリア、スペイン、エセ、ア、ウ ウパダシチニブの調製のための方法及び中間体

Family Cites Families (13)

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AR044010A1 (es) 2003-04-11 2005-08-24 Janssen Pharmaceutica Nv Uso de derivados de 4-fenil-4- [1h-imidazol-2-il]- piperidina sustituidos como agonistas delta opioideos no peptidos selectivos, con actividad antidepresiva y ansiolitica
CN101815512B (zh) 2007-10-04 2013-04-24 弗·哈夫曼-拉罗切有限公司 环丙基芳基酰胺衍生物和其用途
KR101925971B1 (ko) 2011-01-28 2018-12-06 에스케이바이오팜 주식회사 피리돈 유도체 및 이를 포함하는 약학적 조성물
WO2012103583A1 (en) 2011-02-02 2012-08-09 Bionomics Limited Positive allosteric modulators of the alpha 7 nicotinic acetylcholine receptor and uses thereof.
UA111746C2 (uk) 2011-07-08 2016-06-10 Х. Луннбек А/С Позитивні алостеричні модулятори нікотинового рецептора ацетилхоліну
HRP20180913T1 (hr) 2011-07-08 2018-07-27 H. Lundbeck A/S Pozitivni alosterni modulatori receptora nikotinskog acetilkolina
WO2014006117A1 (en) 2012-07-06 2014-01-09 H. Lundbeck A/S New positive allosteric modulators of nicotinic acetylcholine receptor
US20150175534A1 (en) 2012-08-01 2015-06-25 Merck Sharp & Dohme Corp. Alpha-7 NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS AND USES THEROF-I
CN104837820A (zh) 2012-10-02 2015-08-12 大日本住友制药株式会社 咪唑衍生物
CN104837811A (zh) 2012-12-10 2015-08-12 H.隆德贝克有限公司 烟碱乙酰胆碱受体的新的正向別构调节剂
US10208081B2 (en) 2014-11-26 2019-02-19 Enanta Pharmaceuticals, Inc. Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof
US10800780B2 (en) 2015-12-24 2020-10-13 Genentech, Inc. TDO2 Inhibitors
CR20180452A (es) * 2016-03-22 2019-02-06 Merck Sharp & Dohme Moduladores alostéricos de receptores de acetilcolina nicotícos

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PH12020551779A1 (en) 2021-06-07
GEP20227409B (en) 2022-09-12
JP7073533B2 (ja) 2022-05-23
US11332463B2 (en) 2022-05-17
UA126834C2 (uk) 2023-02-08
CR20200509A (es) 2020-12-23
MY205690A (en) 2024-11-06
ZA202006507B (en) 2025-06-25
SI3788043T1 (sl) 2025-01-31
TWI839355B (zh) 2024-04-21
CN112119076A (zh) 2020-12-22
KR102587811B1 (ko) 2023-10-11
PE20210052A1 (es) 2021-01-08
PL3788043T3 (pl) 2025-03-10
CL2020002820A1 (es) 2021-02-19
LT3788043T (lt) 2024-12-27
IL278154B2 (en) 2025-06-01
CA3098583C (en) 2023-05-16
CN112119076B (zh) 2025-01-10
BR112020022088A8 (pt) 2023-02-07
CA3098583A1 (en) 2019-11-07
FI3788043T3 (fi) 2025-01-15
CL2021001795A1 (es) 2021-12-24
IL278154A (en) 2020-11-30
AU2019262917B2 (en) 2021-12-23
GEAP202215499A (en) 2022-05-10
ECSP20067907A (es) 2021-02-26
HRP20241704T1 (hr) 2025-02-14
ES2995040T3 (en) 2025-02-05
IL278154B1 (en) 2025-02-01
PT3788043T (pt) 2024-12-03
RS66290B1 (sr) 2025-01-31
AR115065A1 (es) 2020-11-25
MA52482A (fr) 2021-03-10
TW202014419A (zh) 2020-04-16
SG11202010459XA (en) 2020-11-27
BR112020022088A2 (pt) 2021-02-02
MA52482B1 (fr) 2024-12-31
KR20210005697A (ko) 2021-01-14
US20210070745A1 (en) 2021-03-11
EA202092608A1 (ru) 2021-03-02
EP3788043A1 (en) 2021-03-10
MD3788043T2 (ro) 2025-03-31
MX2020011489A (es) 2020-12-07
JOP20200272A1 (ar) 2020-11-01
WO2019212927A1 (en) 2019-11-07
NZ768954A (en) 2025-06-27
JP2021523102A (ja) 2021-09-02
EP3788043B1 (en) 2024-11-06
NI202000074A (es) 2021-03-05
HUE070339T2 (hu) 2025-05-28
CO2020013462A2 (es) 2020-11-10
AU2019262917A1 (en) 2020-11-05

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