PE20200665A1 - Compuestos espirociclicos y sus metodos de preparacion y uso - Google Patents
Compuestos espirociclicos y sus metodos de preparacion y usoInfo
- Publication number
- PE20200665A1 PE20200665A1 PE2020000297A PE2020000297A PE20200665A1 PE 20200665 A1 PE20200665 A1 PE 20200665A1 PE 2020000297 A PE2020000297 A PE 2020000297A PE 2020000297 A PE2020000297 A PE 2020000297A PE 20200665 A1 PE20200665 A1 PE 20200665A1
- Authority
- PE
- Peru
- Prior art keywords
- alkyl
- compound
- co2h
- compounds
- alkenyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title abstract 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 6
- 229910052736 halogen Inorganic materials 0.000 abstract 5
- 150000002367 halogens Chemical group 0.000 abstract 5
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 abstract 4
- UKHJNJFJCGBKSF-UHFFFAOYSA-N 2,5-diazabicyclo[2.2.1]heptane Chemical compound C1NC2CNC1C2 UKHJNJFJCGBKSF-UHFFFAOYSA-N 0.000 abstract 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- 206010065390 Inflammatory pain Diseases 0.000 abstract 1
- 102100029814 Monoglyceride lipase Human genes 0.000 abstract 1
- 101710116393 Monoglyceride lipase Proteins 0.000 abstract 1
- 150000001204 N-oxides Chemical class 0.000 abstract 1
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 208000004296 neuralgia Diseases 0.000 abstract 1
- 208000021722 neuropathic pain Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- 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
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/36—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 no double bonds between ring members or between ring members and non-ring members 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- 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
- 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
- C07D401/14—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 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
- C07D471/10—Spiro-condensed 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
- 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
- C07D487/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
La presente invencion se refiere a compuestos espirociclicos de formulas (I), (I'), (II), (III), (IV), (VI), (V), (V'), (VII), (VIII) y a sus solvatos, hidratos, tautomeros, esteroisomeros, N-oxidos y sales farmaceutica aceptables, donde: i) En el compuesto (I), Y es -CH2- o -C(O)-; R1 y R2 son H o alquilo C1-C6; R3 es alquilo C1-C6, halogeno, entre otros; R4 es -alquinileno C2-alquilo C1-C6-CO2H y cicloalquilo C3-C8-CO2H; w es 0 a 4; n y m son 0 o 1; p y q son 0 a 2, donde cuando q es 0, p es 2; ii) En el compuesto de formula (I'), Y es -CH2-; R1 y R2 son H o alquilo C1-C6; R3 son alquilo C1-C6, halogeno, entre otros; R4 es -piperazin-CH2-CO2H, -(2,5-diazabiciclo[2.2.1]heptano)-CH2-CO2H, entre otros; w es 0 a 4; n y m son 0 o 1; p y q son 0 a 2, donde cuando q es 0, p es 2; iii) En el compuesto (II), Y es -CH2- o -C(O)-; R3 es alquilo C1-C6, alquenilo C1-C6, entre otros; p es 0 a 5; iv) En el compuesto (III), Y es -CH2- o -C(O)-; R3 es alquilo C1-C6, alquenilo C1-C6, entre otros; p es 0 a 5; v) En el compuesto de formula (IV), R1 y R2 son H o alquilo C1-C6; R3 es alquilo C1-C6, alquenilo C1-C6, entre otros; p es 0 a 5; n es 0 o 1; m es 1 o 2; donde cuando n es 0, m es 2 y cuando n es 1, m es 1; vi) En el compuesto de formula (VI), R3 es alquilo C1-C6, alquenilo C1-C6, entre otros; vii) En el compuesto (V), X es -O- o -N(R11)-; R1 es H o alquilo C1-C6; R2 es alquilo C1-C6; R3 es alquilo C1-C6, alquenilo C2-C6, entre otros; R11 es H, alquilo C1-C6, entre otros; p es 0 a 5 y v es 0 o 1; viii) En el compuesto (V'), X es -O- o -N(R11)-; R1 es H o alquilo C1-C6; R2 es alquilo C1-C6; R3 es alquilo C1-C6, halogeno, entre otros; R4 es -piperazin-CH2-CO2H, -(2,5-diazabiciclo[2.2.1]heptano)-CH2-CO2H, entre otros; R11 es H o alquilo C1-C6; p es 0 a 4; v es 0 o 1; ix) En el compuesto (VII), R1 es octahidropirrolo[3,4-c]pirrolo-R6, entre otros, donde R6 es alquilo C1-C6, entre otros; R2 es alquilo C1-C6, halogeno, entre otros; p es 0 a 4; q es 1 o 2; x) En el compuesto (VIII), R1 es octahidropirrolo[3,4-c]pirrolo-R6, entre otros, donde R6 es alquilo C1-C6, entre otros; R2 es alquilo C1-C6, halogeno, entre otros; p es 0 a 4. Son compuestos preferidos los compuestos a), b), c), d), entre otros. Tambien se refiere a una composicion farmaceutica. Dichos compuestos son moduladores de MAGL, siendo utiles en el tratamiento de dolor neuropatico, dolor inflamatorio, entre otros.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762551714P | 2017-08-29 | 2017-08-29 | |
| PCT/US2018/048388 WO2019046330A1 (en) | 2017-08-29 | 2018-08-28 | SPIROCYCLIC COMPOUNDS AND METHODS OF PREPARATION AND USE THEREOF |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20200665A1 true PE20200665A1 (es) | 2020-06-11 |
Family
ID=65526036
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2020000297A PE20200665A1 (es) | 2017-08-29 | 2018-08-28 | Compuestos espirociclicos y sus metodos de preparacion y uso |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US11161856B2 (es) |
| EP (1) | EP3675848B1 (es) |
| JP (1) | JP7177825B2 (es) |
| KR (1) | KR20200046053A (es) |
| CN (1) | CN111032034B (es) |
| AU (1) | AU2018326497A1 (es) |
| BR (1) | BR112020003946A2 (es) |
| CA (1) | CA3072926A1 (es) |
| CL (1) | CL2020000463A1 (es) |
| CO (1) | CO2020001715A2 (es) |
| CR (1) | CR20200088A (es) |
| DO (1) | DOP2020000040A (es) |
| EA (1) | EA202090296A1 (es) |
| EC (1) | ECSP20013332A (es) |
| ES (1) | ES2914363T3 (es) |
| IL (1) | IL272578A (es) |
| JO (1) | JOP20200022A1 (es) |
| MA (1) | MA50045A (es) |
| MX (1) | MX2020002254A (es) |
| PE (1) | PE20200665A1 (es) |
| PH (1) | PH12020500371A1 (es) |
| RU (1) | RU2020107039A (es) |
| SG (1) | SG11202000984YA (es) |
| WO (1) | WO2019046330A1 (es) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3698782B1 (en) | 2012-01-06 | 2024-05-15 | H. Lundbeck A/S | Carbamate compounds for use in therapy |
| CN109496213B (zh) | 2016-05-12 | 2022-03-04 | H.隆德贝克有限公司 | 螺环化合物及其制备和使用方法 |
| ES2892952T3 (es) | 2016-09-19 | 2022-02-07 | H Lundbeck As | Carbamatos de piperazina como moduladores del MAGL y/o ABHD6 y su uso |
| JOP20190107A1 (ar) | 2016-11-16 | 2019-05-09 | Lundbeck La Jolla Research Center Inc | مثبطات أحادي أسيل جليسرول ليباز (magl) |
| JOP20200022A1 (ar) | 2017-08-29 | 2020-02-02 | Lundbeck La Jolla Research Center Inc | مركبات حلقية لولبية وطرق تصنيعها واستخدامها |
| KR20200046061A (ko) | 2017-08-29 | 2020-05-06 | 룬드벡 라 졸라 리서치 센터 인코포레이티드 | 스피로사이클 화합물 및 이를 제조하고 사용하는 방법 |
| BR112020000863A2 (pt) | 2018-05-15 | 2020-12-08 | Lundbeck La Jolla Research Center, Inc. | Inibidores de magl |
| CN111505410B (zh) * | 2020-04-02 | 2022-07-29 | 矽力杰半导体技术(杭州)有限公司 | 调光模式检测电路、方法和无调光检测电路及照明系统 |
| BR112021025516A2 (pt) | 2020-04-21 | 2022-11-01 | H Lundbeck As | Processos para a fabricação de 4-(2-(pirrolidin-1-il)-4-(trifluorometil)benzil)piperazina-1-carboxilato de 1,1,1,3,3,3-hexafluoropropan-2-ila e da forma 2 do sal monocloridrato do mesmo |
| US11434222B2 (en) * | 2020-11-13 | 2022-09-06 | H. Lundbeck A/S | MAGL inhibitors |
| PH12023552079A1 (en) | 2021-01-29 | 2024-01-22 | Cedilla Therapeutics Inc | Cdk2 inhibitors and methods of using the same |
| IL309571A (en) | 2021-06-26 | 2024-02-01 | Cedilla Therapeutics Inc | Cdk2 inhibitors and methods of using the same |
| EP4457213A1 (en) | 2021-12-29 | 2024-11-06 | Psy Therapeutics, Inc. | Inhibiting monoacylglycerol lipase (magl) |
| US12378219B2 (en) | 2022-05-04 | 2025-08-05 | H. Lundbeck A/S | Crystalline forms of a MAGL inhibitor |
| WO2024168426A1 (en) | 2023-02-13 | 2024-08-22 | Apogee Pharmaceuticals, Inc. | Small molecules as monoacylglycerol lipase (magl) inhibitors, compositions and use thereof |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002070523A1 (en) | 2001-03-07 | 2002-09-12 | Pfizer Products Inc. | Modulators of chemokine receptor activity |
| CA2665804A1 (en) * | 2006-08-23 | 2008-02-28 | Astellas Pharma Inc. | Urea compound or salt thereof |
| KR20100122508A (ko) | 2008-03-05 | 2010-11-22 | 타가셉트 인코포레이티드 | 디아자비시클로알칸의 니코틴 아세틸콜린 수용체 서브-타입 선택성 아미드 |
| US20120083476A1 (en) | 2009-06-05 | 2012-04-05 | Janssen Pharmaceutica Nv | Heteroaryl-substituted spirocyclic diamine urea modulators of fatty acid amide hydrolase |
| PH12012500796A1 (en) | 2009-10-23 | 2012-11-26 | Janssen Pharmaceutica Nv | Disubstituted octahydropyrrolo [3,4-c] pyrroles as orexin receptor modulators |
| JP2013521290A (ja) | 2010-03-04 | 2013-06-10 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｍｇｌｕｒ２の正のアロステリックモジュレータ |
| FR2960875B1 (fr) | 2010-06-04 | 2012-12-28 | Sanofi Aventis | Derives de carbamates d'hexafluoroisopropyle, leur preparation et leur application en therapeutique |
| EP2444084A1 (en) | 2010-10-21 | 2012-04-25 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Use of PI3K inibitors for the treatment of obesity |
| EP3698782B1 (en) * | 2012-01-06 | 2024-05-15 | H. Lundbeck A/S | Carbamate compounds for use in therapy |
| HRP20191937T1 (hr) | 2012-09-25 | 2020-01-10 | F. Hoffmann - La Roche Ag | Derivati heksahidropirolo [3,4-c]pirola i srodni spojevi kao inhibitori autotaksina (atx) i kao inhibitori proizvodnje lizofosfatidne kiseline (lpa) za liječenje npr. bubrežnih bolesti |
| CN105517547A (zh) | 2013-07-03 | 2016-04-20 | 阿比德治疗公司 | 吡咯并吡咯氨基甲酸酯和相关的有机化合物、药物组合物及其医学用途 |
| JP2018513119A (ja) * | 2015-03-18 | 2018-05-24 | アビデ セラピューティクス，インク． | ピペラジンカルバメート、およびピペラジンカルバメートを製造ならびに使用する方法 |
| CN107849017B (zh) | 2015-07-31 | 2021-03-30 | 辉瑞公司 | 作为magl抑制剂的1,1,1-三氟-3-羟基丙-2-基氨基甲酸酯衍生物及1,1,1-三氟-4-羟基丁-2-基氨基甲酸酯衍生物 |
| WO2017087854A1 (en) | 2015-11-20 | 2017-05-26 | Abide Therapeutics, Inc. | Pyrazole compounds and methods of making and using same |
| CN109496213B (zh) | 2016-05-12 | 2022-03-04 | H.隆德贝克有限公司 | 螺环化合物及其制备和使用方法 |
| JOP20190107A1 (ar) | 2016-11-16 | 2019-05-09 | Lundbeck La Jolla Research Center Inc | مثبطات أحادي أسيل جليسرول ليباز (magl) |
| KR20200046061A (ko) | 2017-08-29 | 2020-05-06 | 룬드벡 라 졸라 리서치 센터 인코포레이티드 | 스피로사이클 화합물 및 이를 제조하고 사용하는 방법 |
| JOP20200022A1 (ar) | 2017-08-29 | 2020-02-02 | Lundbeck La Jolla Research Center Inc | مركبات حلقية لولبية وطرق تصنيعها واستخدامها |
-
2018
- 2018-08-28 JO JOP/2020/0022A patent/JOP20200022A1/ar unknown
- 2018-08-28 ES ES18852217T patent/ES2914363T3/es active Active
- 2018-08-28 MA MA050045A patent/MA50045A/fr unknown
- 2018-08-28 BR BR112020003946-2A patent/BR112020003946A2/pt not_active Application Discontinuation
- 2018-08-28 CA CA3072926A patent/CA3072926A1/en not_active Abandoned
- 2018-08-28 AU AU2018326497A patent/AU2018326497A1/en not_active Abandoned
- 2018-08-28 EP EP18852217.1A patent/EP3675848B1/en active Active
- 2018-08-28 RU RU2020107039A patent/RU2020107039A/ru unknown
- 2018-08-28 MX MX2020002254A patent/MX2020002254A/es unknown
- 2018-08-28 CR CR20200088A patent/CR20200088A/es unknown
- 2018-08-28 CN CN201880054296.1A patent/CN111032034B/zh active Active
- 2018-08-28 WO PCT/US2018/048388 patent/WO2019046330A1/en not_active Ceased
- 2018-08-28 US US16/642,713 patent/US11161856B2/en active Active
- 2018-08-28 SG SG11202000984YA patent/SG11202000984YA/en unknown
- 2018-08-28 PE PE2020000297A patent/PE20200665A1/es unknown
- 2018-08-28 JP JP2020512612A patent/JP7177825B2/ja active Active
- 2018-08-28 EA EA202090296A patent/EA202090296A1/ru unknown
- 2018-08-28 KR KR1020207007712A patent/KR20200046053A/ko not_active Withdrawn
-
2020
- 2020-02-10 IL IL272578A patent/IL272578A/en unknown
- 2020-02-14 CO CONC2020/0001715A patent/CO2020001715A2/es unknown
- 2020-02-21 DO DO2020000040A patent/DOP2020000040A/es unknown
- 2020-02-21 EC ECSENADI202013332A patent/ECSP20013332A/es unknown
- 2020-02-24 PH PH12020500371A patent/PH12020500371A1/en unknown
- 2020-02-25 CL CL2020000463A patent/CL2020000463A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EA202090296A1 (ru) | 2020-08-03 |
| PH12020500371A1 (en) | 2020-12-07 |
| CA3072926A1 (en) | 2019-03-07 |
| JOP20200022A1 (ar) | 2020-02-02 |
| CR20200088A (es) | 2020-04-08 |
| CL2020000463A1 (es) | 2020-07-10 |
| EP3675848A1 (en) | 2020-07-08 |
| EP3675848A4 (en) | 2021-03-10 |
| ECSP20013332A (es) | 2020-04-22 |
| DOP2020000040A (es) | 2020-08-31 |
| MX2020002254A (es) | 2020-07-20 |
| SG11202000984YA (en) | 2020-03-30 |
| JP2020532547A (ja) | 2020-11-12 |
| RU2020107039A (ru) | 2021-09-30 |
| MA50045A (fr) | 2020-07-08 |
| CO2020001715A2 (es) | 2020-02-28 |
| AU2018326497A1 (en) | 2020-02-20 |
| ES2914363T3 (es) | 2022-06-09 |
| EP3675848B1 (en) | 2022-03-23 |
| BR112020003946A2 (pt) | 2020-09-08 |
| US11161856B2 (en) | 2021-11-02 |
| JP7177825B2 (ja) | 2022-11-24 |
| CN111032034A (zh) | 2020-04-17 |
| US20210214375A1 (en) | 2021-07-15 |
| IL272578A (en) | 2020-03-31 |
| KR20200046053A (ko) | 2020-05-06 |
| WO2019046330A1 (en) | 2019-03-07 |
| CN111032034B (zh) | 2023-05-02 |
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