BR112020022088A8 - Moduladores alostéricos de espiropiperidina de receptores nicotínicos de acetilcolina - Google Patents
Moduladores alostéricos de espiropiperidina de receptores nicotínicos de acetilcolinaInfo
- Publication number
- BR112020022088A8 BR112020022088A8 BR112020022088A BR112020022088A BR112020022088A8 BR 112020022088 A8 BR112020022088 A8 BR 112020022088A8 BR 112020022088 A BR112020022088 A BR 112020022088A BR 112020022088 A BR112020022088 A BR 112020022088A BR 112020022088 A8 BR112020022088 A8 BR 112020022088A8
- Authority
- BR
- Brazil
- Prior art keywords
- spiropiperidine
- nicotin
- acetylcholine receptors
- allosteric modulators
- compounds
- Prior art date
Links
- JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical compound C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 title abstract 2
- POPPVIRYGJQIOF-UHFFFAOYSA-N 2-acetyloxyethyl(trimethyl)azanium;3-(1-methylpyrrolidin-2-yl)pyridine Chemical compound CC(=O)OCC[N+](C)(C)C.CN1CCCC1C1=CC=CN=C1 POPPVIRYGJQIOF-UHFFFAOYSA-N 0.000 title abstract 2
- 108010009685 Cholinergic Receptors Proteins 0.000 title abstract 2
- 102000034337 acetylcholine receptors Human genes 0.000 title abstract 2
- 230000003281 allosteric effect Effects 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 3
- 208000024827 Alzheimer disease Diseases 0.000 abstract 1
- 208000028698 Cognitive impairment Diseases 0.000 abstract 1
- 208000012661 Dyskinesia Diseases 0.000 abstract 1
- 206010061218 Inflammation Diseases 0.000 abstract 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 abstract 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 abstract 1
- 208000018737 Parkinson disease Diseases 0.000 abstract 1
- 208000015114 central nervous system disease Diseases 0.000 abstract 1
- 208000010877 cognitive disease Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 201000000980 schizophrenia Diseases 0.000 abstract 1
Classifications
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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
- A61K31/54—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
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- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (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)
Abstract
MODULADORES ALOSTÉRICOS DE ESPIROPIPERIDINA DE RECEPTORES NICOTÍNICOS DE ACETILCOLINA. A presente invenção está relacionada a compostos de fórmula I que são úteis como moduladores de ¿7 nAChR, composições compreendendo tais compostos e o uso de tais compostos para prevenir, tratar ou melhorar doenças, particularmente distúrbios do sistema nervoso central, tais como comprometimentos cognitivos em doença de Alzheimer, doença de Parkinson e esquizofrenia, bem como para discinesia induzida por L-DOPA e inflamação.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862665091P | 2018-05-01 | 2018-05-01 | |
| US62/665,091 | 2018-05-01 | ||
| PCT/US2019/029561 WO2019212927A1 (en) | 2018-05-01 | 2019-04-29 | Spiropiperidine allosteric modulators of nicotinic acetylcholine receptors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112020022088A2 BR112020022088A2 (pt) | 2021-02-02 |
| BR112020022088A8 true BR112020022088A8 (pt) | 2023-02-07 |
Family
ID=66429709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112020022088A BR112020022088A8 (pt) | 2018-05-01 | 2019-04-29 | Moduladores alostéricos de espiropiperidina de receptores nicotínicos de acetilcolina |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US11332463B2 (pt) |
| EP (1) | EP3788043B1 (pt) |
| JP (1) | JP7073533B2 (pt) |
| KR (1) | KR102587811B1 (pt) |
| CN (1) | CN112119076A (pt) |
| AR (1) | AR115065A1 (pt) |
| AU (1) | AU2019262917B2 (pt) |
| BR (1) | BR112020022088A8 (pt) |
| CA (1) | CA3098583C (pt) |
| CL (2) | CL2020002820A1 (pt) |
| CO (1) | CO2020013462A2 (pt) |
| CR (1) | CR20200509A (pt) |
| EA (1) | EA202092608A1 (pt) |
| EC (1) | ECSP20067907A (pt) |
| GE (1) | GEP20227409B (pt) |
| IL (1) | IL278154A (pt) |
| JO (1) | JOP20200272A1 (pt) |
| MA (1) | MA52482A (pt) |
| MX (1) | MX2020011489A (pt) |
| NI (1) | NI202000074A (pt) |
| PE (1) | PE20210052A1 (pt) |
| PH (1) | PH12020551779A1 (pt) |
| SG (1) | SG11202010459XA (pt) |
| TW (1) | TWI839355B (pt) |
| UA (1) | UA126834C2 (pt) |
| WO (1) | WO2019212927A1 (pt) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018165520A1 (en) | 2017-03-10 | 2018-09-13 | Vps-3, Inc. | Metalloenzyme inhibitor compounds |
| WO2020223136A1 (en) * | 2019-05-02 | 2020-11-05 | Merck Sharp & Dohme Corp. | Spiropiperidine allosteric modulators of nicotinic acetylcholine receptors |
| US20220396571A1 (en) * | 2019-11-05 | 2022-12-15 | Merck Sharp & Dohme Corp. | Spiropiperidine allosteric modulators of nicotinic acetylcholine receptors |
| EP4077276A1 (en) * | 2019-12-19 | 2022-10-26 | Curia Spain S.A.U. | Process and intermediates for the preparation of upadacitinib |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| KR101178674B1 (ko) | 2007-10-04 | 2012-08-30 | 에프. 호프만-라 로슈 아게 | 사이클로프로필 아릴 아마이드 유도체 및 이의 용도 |
| KR101925971B1 (ko) | 2011-01-28 | 2018-12-06 | 에스케이바이오팜 주식회사 | 피리돈 유도체 및 이를 포함하는 약학적 조성물 |
| EP2670731B1 (en) | 2011-02-02 | 2016-05-25 | 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 |
| US8598213B2 (en) | 2011-07-08 | 2013-12-03 | H. Lundbeck A/S | Positive allosteric modulators of nicotinic acetylcholine receptor |
| WO2014006120A1 (en) | 2012-07-06 | 2014-01-09 | H. Lundbeck A/S | New positive allosteric modulators of nicotinic acetylcholine receptor |
| CN104884432A (zh) | 2012-08-01 | 2015-09-02 | 默沙东公司 | α7烟碱乙酰胆碱受体调节剂及其用途-I |
| US20150259344A1 (en) | 2012-10-02 | 2015-09-17 | Dainippon Sumitomo Pharma Co., Ltd. | Imidazole derivative |
| US20150315130A1 (en) | 2012-12-10 | 2015-11-05 | H. Lundbeck A/S | New positive allosteric modulators of nicotinic acetylcholine receptor |
| US10208081B2 (en) | 2014-11-26 | 2019-02-19 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof |
| CN115010712A (zh) | 2015-12-24 | 2022-09-06 | 基因泰克公司 | Tdo2抑制剂 |
| DK3433234T3 (da) * | 2016-03-22 | 2022-01-03 | Merck Sharp & Dohme | Allosteriske modulatorer af nicotinacetylcholinreceptorer |
-
2019
- 2019-04-29 CA CA3098583A patent/CA3098583C/en active Active
- 2019-04-29 AR ARP190101126A patent/AR115065A1/es unknown
- 2019-04-29 US US17/049,653 patent/US11332463B2/en active Active
- 2019-04-29 MX MX2020011489A patent/MX2020011489A/es unknown
- 2019-04-29 PE PE2020001722A patent/PE20210052A1/es unknown
- 2019-04-29 CN CN201980029616.2A patent/CN112119076A/zh active Pending
- 2019-04-29 CR CR20200509A patent/CR20200509A/es unknown
- 2019-04-29 MA MA052482A patent/MA52482A/fr unknown
- 2019-04-29 UA UAA202007589A patent/UA126834C2/uk unknown
- 2019-04-29 SG SG11202010459XA patent/SG11202010459XA/en unknown
- 2019-04-29 EP EP19722488.4A patent/EP3788043B1/en active Active
- 2019-04-29 BR BR112020022088A patent/BR112020022088A8/pt unknown
- 2019-04-29 JO JOP/2020/0272A patent/JOP20200272A1/ar unknown
- 2019-04-29 WO PCT/US2019/029561 patent/WO2019212927A1/en active Application Filing
- 2019-04-29 EA EA202092608A patent/EA202092608A1/ru unknown
- 2019-04-29 JP JP2020560807A patent/JP7073533B2/ja active Active
- 2019-04-29 GE GEAP201915499A patent/GEP20227409B/en unknown
- 2019-04-29 TW TW108114867A patent/TWI839355B/zh active
- 2019-04-29 AU AU2019262917A patent/AU2019262917B2/en active Active
- 2019-04-29 KR KR1020207034124A patent/KR102587811B1/ko active IP Right Grant
-
2020
- 2020-10-19 IL IL278154A patent/IL278154A/en unknown
- 2020-10-26 EC ECSENADI202067907A patent/ECSP20067907A/es unknown
- 2020-10-26 CO CONC2020/0013462A patent/CO2020013462A2/es unknown
- 2020-10-27 PH PH12020551779A patent/PH12020551779A1/en unknown
- 2020-10-27 NI NI202000074A patent/NI202000074A/es unknown
- 2020-10-29 CL CL2020002820A patent/CL2020002820A1/es unknown
-
2021
- 2021-07-06 CL CL2021001795A patent/CL2021001795A1/es unknown
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