AR100442A1 - Derivados de pirido[1,2-a]pirimidin-4-ona para tratar atrofia muscular espinal - Google Patents
Derivados de pirido[1,2-a]pirimidin-4-ona para tratar atrofia muscular espinalInfo
- Publication number
- AR100442A1 AR100442A1 ARP150101500A ARP150101500A AR100442A1 AR 100442 A1 AR100442 A1 AR 100442A1 AR P150101500 A ARP150101500 A AR P150101500A AR P150101500 A ARP150101500 A AR P150101500A AR 100442 A1 AR100442 A1 AR 100442A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- heterocycloalkyl
- cycloalkyl
- hydrogen
- amino
- Prior art date
Links
Classifications
-
- 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
-
- 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
- A61K31/495—Heterocyclic 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines 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
- 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
- A61K31/495—Heterocyclic 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- 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
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Además, se refiere a la fabricación de compuestos de fórmula (1), a composiciones farmacéuticas que los comprenden y a su uso como medicamentos para tratar o prevenir la AME. Reivindicación 1: El compuesto de fórmula (1) en la que R¹ es hidrógeno o alquilo C₁₋₇; R² es hidrógeno, ciano, alquilo C₁₋₇, haloalquilo C₁₋₇ o cicloalquilo C₃₋₈; R³ es hidrógeno, alquilo C₁₋₇, o cicloalquilo C₃₋₈; A es N-heterocicloalquilo o NR¹²R¹³, en el que N-heterocicloalquilo comprende 1 ó 2 átomos de anillo de nitrógeno y está opcionalmente sustituido con 1, 2, 3 ó 4 sustituyentes seleccionados de R¹⁴; R¹² es heterocicloalquilo que comprende 1 átomo de anillo de nitrógeno, en el que heterocicloalquilo está opcionalmente sustituido con 1, 2, 3 ó 4 sustituyentes seleccionados de R¹⁴; R¹³ es hidrógeno, alquilo C₁₋₇₀ cicloalquilo C₃₋₈; R¹⁴ se selecciona independientemente de nitrógeno, alquilo C₁₋₇, amino, amino-alquilo C₁₋₇, cicloalquilo y heterocicloalquilo C₃₋₈ o dos R¹⁴ juntos forman alquileno C₁₋₇; con la salvedad de que si A es N-heterocicloalquilo que comprende solo 1 átomo de anillo de nitrógeno, entonces al menos un sustituyente R¹⁴ es amino o amino-alquilo C₁₋₇; y sales farmacéuticamente aceptables de los mismos.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461993839P | 2014-05-15 | 2014-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR100442A1 true AR100442A1 (es) | 2016-10-05 |
Family
ID=53175048
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP150101500A AR100442A1 (es) | 2014-05-15 | 2015-05-14 | Derivados de pirido[1,2-a]pirimidin-4-ona para tratar atrofia muscular espinal |
| ARP230103289A AR131260A2 (es) | 2014-05-15 | 2023-12-01 | Compuestos para tratar atrofia muscular espinal |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP230103289A AR131260A2 (es) | 2014-05-15 | 2023-12-01 | Compuestos para tratar atrofia muscular espinal |
Country Status (36)
| Country | Link |
|---|---|
| US (1) | US9969754B2 (es) |
| EP (3) | EP3663296B1 (es) |
| JP (1) | JP6236173B2 (es) |
| KR (2) | KR102256013B1 (es) |
| CN (1) | CN106459092B (es) |
| AR (2) | AR100442A1 (es) |
| AU (1) | AU2015261046C1 (es) |
| BR (1) | BR112016026205B1 (es) |
| CA (1) | CA2948561C (es) |
| CL (1) | CL2016002836A1 (es) |
| CR (1) | CR20160518A (es) |
| DK (1) | DK3143025T3 (es) |
| EA (2) | EA035068B1 (es) |
| ES (2) | ES2949660T3 (es) |
| FR (1) | FR21C1039I2 (es) |
| HR (2) | HRP20192159T1 (es) |
| HU (2) | HUE046491T2 (es) |
| IL (2) | IL248653B (es) |
| LT (1) | LTC3143025I2 (es) |
| MA (2) | MA51988A (es) |
| MX (1) | MX371050B (es) |
| MY (1) | MY174284A (es) |
| NL (1) | NL301128I2 (es) |
| NO (2) | NO2021035I1 (es) |
| NZ (1) | NZ725008A (es) |
| PE (1) | PE20170128A1 (es) |
| PH (1) | PH12016502081B1 (es) |
| PL (2) | PL3143025T3 (es) |
| PT (1) | PT3143025T (es) |
| RS (1) | RS59718B1 (es) |
| SG (1) | SG11201609497TA (es) |
| SI (2) | SI3143025T1 (es) |
| TW (1) | TWI667239B (es) |
| UA (1) | UA119670C2 (es) |
| WO (1) | WO2015173181A1 (es) |
| ZA (1) | ZA201607026B (es) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3406252B1 (en) | 2012-02-10 | 2020-05-13 | PTC Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| WO2015024876A2 (en) | 2013-08-19 | 2015-02-26 | F. Hoffmann-La Roche Ag | Screening method |
| US10882868B2 (en) * | 2014-05-15 | 2021-01-05 | Hoffmann-La Roche Inc. | Compounds for treating spinal muscular atrophy |
| CN107635999B (zh) | 2015-05-20 | 2020-09-25 | 豪夫迈·罗氏有限公司 | 用于治疗脊髓性肌萎缩的化合物 |
| EP4249472A3 (en) | 2015-05-30 | 2023-12-13 | PTC Therapeutics, Inc. | Methods for modulating rna splicing |
| AR106652A1 (es) * | 2015-11-12 | 2018-02-07 | Hoffmann La Roche | Compuestos para tratar la esclerosis lateral amiotrófica |
| JP6659841B2 (ja) * | 2015-11-12 | 2020-03-04 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 脊髄性筋萎縮症を処置するための組成物 |
| EA201800367A1 (ru) | 2015-12-10 | 2019-02-28 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Способы лечения болезни хантингтона |
| WO2017097728A1 (en) | 2015-12-10 | 2017-06-15 | F. Hoffmann-La Roche Ag | Bridged piperidine derivatives |
| EP3544435A4 (en) * | 2016-11-28 | 2020-11-04 | PTC Therapeutics, Inc. | RNA SPLICE MODULATION PROCESSES |
| JP7376471B2 (ja) | 2017-06-05 | 2023-11-08 | ピーティーシー セラピューティクス, インコーポレイテッド | ハンチントン病を処置するための化合物 |
| WO2018232039A1 (en) | 2017-06-14 | 2018-12-20 | Ptc Therapeutics, Inc. | Methods for modifying rna splicing |
| US11395822B2 (en) | 2017-06-28 | 2022-07-26 | Ptc Therapeutics, Inc. | Methods for treating Huntington's disease |
| BR112019027717A2 (pt) | 2017-06-28 | 2020-07-28 | Ptc Therapeutics, Inc. | métodos para tratar a doença de huntington |
| EP4663641A3 (en) * | 2017-09-22 | 2026-01-07 | F. Hoffmann-La Roche AG | Process for the prepration of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one derivatives |
| KR102761837B1 (ko) | 2017-10-03 | 2025-02-05 | 에프. 호프만-라 로슈 아게 | 척수성 근위축증의 새로운 치료법 |
| AU2019243048A1 (en) | 2018-03-27 | 2020-10-15 | Ptc Therapeutics, Inc. | Compounds for treating Huntington's disease |
| JOP20200338A1 (ar) | 2018-06-27 | 2020-12-24 | Reborna Biosciences Inc | عامل وقائي أو علاجي للضمور العضلي نخاعي المنشأ |
| SI3814357T1 (sl) | 2018-06-27 | 2024-09-30 | Ptc Therapeutics, Inc. | Heterociklične in heteroarilne spojine za zdravljenje Huntingtonove bolezni |
| BR112020026534A2 (pt) | 2018-06-27 | 2021-03-23 | Ptc Therapeutics, Inc. | Compostos de heteroarila para o tratamento da doença de huntington |
| WO2020005882A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| CN120554385A (zh) * | 2018-10-19 | 2025-08-29 | 豪夫迈·罗氏有限公司 | 新型吡啶并[1,2-a]嘧啶-4-酮衍生物、其制剂及制备方法 |
| WO2020249577A1 (en) | 2019-06-12 | 2020-12-17 | F. Hoffmann-La Roche Ag | New treatment of sma |
| EP4004003A1 (en) * | 2019-07-31 | 2022-06-01 | Teva Pharmaceuticals International GmbH | Solid state forms of risdiplam and process for preparation thereof |
| WO2021207530A1 (en) * | 2020-04-08 | 2021-10-14 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| WO2022048675A1 (zh) * | 2020-09-07 | 2022-03-10 | 苏州科睿思制药有限公司 | Risdiplam晶型及其制备方法和用途 |
| WO2022162107A1 (en) | 2021-02-01 | 2022-08-04 | Sandoz Ag | Crystalline form of risdiplam |
| WO2022194802A1 (en) * | 2021-03-17 | 2022-09-22 | F. Hoffmann-La Roche Ag | New thiadiazolopyrimidone derivatives |
| WO2022194801A1 (en) * | 2021-03-17 | 2022-09-22 | F. Hoffmann-La Roche Ag | New thiazolopyrimidinone derivatives |
| EP4308572B1 (en) * | 2021-03-17 | 2025-04-23 | F. Hoffmann-La Roche AG | New thienopyrimidinone derivatives |
| AU2022237836B2 (en) * | 2021-03-18 | 2024-07-04 | F. Hoffmann-La Roche Ag | Process for preparing risdiplam |
| WO2023057404A1 (en) | 2021-10-06 | 2023-04-13 | F. Hoffmann-La Roche Ag | Novel combined administration |
| WO2023202501A1 (zh) * | 2022-04-18 | 2023-10-26 | 深圳市塔吉瑞生物医药有限公司 | 取代的吡啶并嘧啶酮类化合物及包含该化合物的组合物及其用途 |
| WO2023240236A1 (en) | 2022-06-10 | 2023-12-14 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of spinal muscular atrophy related disorders |
| WO2024069646A1 (en) * | 2022-09-26 | 2024-04-04 | Natco Pharma Limited | Improved process for the preparation of risdiplam and its intermediates |
| WO2024081932A1 (en) | 2022-10-14 | 2024-04-18 | Genentech, Inc. | Methods for treating spinal muscular atrophy |
| IL322038A (en) * | 2023-01-21 | 2025-09-01 | Harman Finochem Ltd | Process for preparing risdiplam, new intermediates, and process for preparing them |
| WO2024218207A1 (en) | 2023-04-20 | 2024-10-24 | F. Hoffmann-La Roche Ag | Thieno[3,2-b]pyridine derivatives |
| AU2024286618A1 (en) | 2023-06-09 | 2025-10-30 | F. Hoffmann-La Roche Ag | Inducible gene expression system |
| CN117050096A (zh) * | 2023-07-17 | 2023-11-14 | 杭州诺澳生物医药科技有限公司 | 一种利司扑兰的制备方法 |
| TW202525295A (zh) * | 2023-10-27 | 2025-07-01 | 瑞士商赫孚孟拉羅股份公司 | 治療脊髓性肌肉萎縮症之新穎組成物 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL331602A1 (en) * | 1996-08-06 | 1999-08-02 | Pfizer | Pyrido- or pyrimido-substituted 6,6- or 6,7-bicyclic derivatives |
| AU2008304231A1 (en) | 2007-09-27 | 2009-04-02 | Albany Molecular Research, Inc. | Isoindoline compounds for the treatment of spinal muscular atrophy and other uses |
| WO2009151546A2 (en) * | 2008-05-27 | 2009-12-17 | Ptc Therapeutics, Inc. | Methods for treating spinal muscular atrophy |
| KR20100012134A (ko) * | 2008-07-28 | 2010-02-08 | 신호열 | 마우스 |
| US8986935B2 (en) | 2008-08-13 | 2015-03-24 | Ptc Therapeutics, Inc. | Methods for treating spinal muscular atrophy |
| US8126566B2 (en) * | 2008-08-14 | 2012-02-28 | Cardiac Pacemakers, Inc. | Performance assessment and adaptation of an acoustic communication link |
| WO2013101974A1 (en) * | 2011-12-30 | 2013-07-04 | Ptc Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| CA2862084C (en) * | 2012-01-26 | 2021-05-11 | Ptc Therapeutics, Inc. | 1h-isochromen-1-one derivatives and compositions thereof for treating spinal muscular atrophy |
| EP3406252B1 (en) * | 2012-02-10 | 2020-05-13 | PTC Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| AU2013289938A1 (en) | 2012-07-13 | 2015-01-29 | Indiana University Research & Technology Corporation | Compounds for treatment of spinal muscular atrophy |
| JP6659841B2 (ja) | 2015-11-12 | 2020-03-04 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 脊髄性筋萎縮症を処置するための組成物 |
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2015
- 2015-05-11 EA EA201692280A patent/EA035068B1/ru active Protection Beyond IP Right Term
- 2015-05-11 KR KR1020217002966A patent/KR102256013B1/ko active Active
- 2015-05-11 MX MX2016014547A patent/MX371050B/es active IP Right Grant
- 2015-05-11 MA MA051988A patent/MA51988A/fr unknown
- 2015-05-11 PT PT157217019T patent/PT3143025T/pt unknown
- 2015-05-11 ES ES19200058T patent/ES2949660T3/es active Active
- 2015-05-11 AU AU2015261046A patent/AU2015261046C1/en active Active
- 2015-05-11 PL PL15721701T patent/PL3143025T3/pl unknown
- 2015-05-11 EP EP19200058.6A patent/EP3663296B1/en active Active
- 2015-05-11 ES ES15721701T patent/ES2761423T3/es active Active
- 2015-05-11 DK DK15721701T patent/DK3143025T3/da active
- 2015-05-11 PH PH1/2016/502081A patent/PH12016502081B1/en unknown
- 2015-05-11 SI SI201531021T patent/SI3143025T1/sl unknown
- 2015-05-11 EA EA202090486A patent/EA202090486A3/ru unknown
- 2015-05-11 SI SI201531952T patent/SI3663296T1/sl unknown
- 2015-05-11 EP EP23169721.0A patent/EP4241772A3/en not_active Withdrawn
- 2015-05-11 KR KR1020167034983A patent/KR102213740B1/ko active Active
- 2015-05-11 CN CN201580027306.9A patent/CN106459092B/zh active Active
- 2015-05-11 HU HUE15721701A patent/HUE046491T2/hu unknown
- 2015-05-11 PE PE2016002128A patent/PE20170128A1/es unknown
- 2015-05-11 SG SG11201609497TA patent/SG11201609497TA/en unknown
- 2015-05-11 MY MYPI2016001903A patent/MY174284A/en unknown
- 2015-05-11 JP JP2016567816A patent/JP6236173B2/ja active Active
- 2015-05-11 CR CR20160518A patent/CR20160518A/es unknown
- 2015-05-11 MA MA39995A patent/MA39995B1/fr unknown
- 2015-05-11 HR HRP20192159TT patent/HRP20192159T1/hr unknown
- 2015-05-11 NZ NZ72500815A patent/NZ725008A/en unknown
- 2015-05-11 BR BR112016026205-0A patent/BR112016026205B1/pt active IP Right Grant
- 2015-05-11 CA CA2948561A patent/CA2948561C/en active Active
- 2015-05-11 EP EP15721701.9A patent/EP3143025B1/en active Active
- 2015-05-11 PL PL19200058.6T patent/PL3663296T3/pl unknown
- 2015-05-11 RS RS20191541A patent/RS59718B1/sr unknown
- 2015-05-11 WO PCT/EP2015/060343 patent/WO2015173181A1/en not_active Ceased
- 2015-05-11 UA UAA201612716A patent/UA119670C2/uk unknown
- 2015-05-11 HR HRP20230637TT patent/HRP20230637T1/hr unknown
- 2015-05-14 AR ARP150101500A patent/AR100442A1/es not_active Application Discontinuation
- 2015-05-14 TW TW104115433A patent/TWI667239B/zh active
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2016
- 2016-10-12 ZA ZA2016/07026A patent/ZA201607026B/en unknown
- 2016-10-31 IL IL24865316A patent/IL248653B/en active IP Right Grant
- 2016-11-08 CL CL2016002836A patent/CL2016002836A1/es unknown
- 2016-11-14 US US15/351,267 patent/US9969754B2/en active Active
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2019
- 2019-10-17 IL IL270027A patent/IL270027B/en active IP Right Grant
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2021
- 2021-09-09 FR FR21C1039C patent/FR21C1039I2/fr active Active
- 2021-09-10 NO NO2021035C patent/NO2021035I1/no unknown
- 2021-09-14 LT LTPA2021010C patent/LTC3143025I2/lt unknown
- 2021-09-14 HU HUS2100037C patent/HUS2100037I1/hu unknown
- 2021-09-15 NL NL301128C patent/NL301128I2/nl unknown
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2023
- 2023-12-01 AR ARP230103289A patent/AR131260A2/es unknown
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2025
- 2025-08-14 NO NO2025038C patent/NO2025038I1/no unknown
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