JP6959252B2 - Dub阻害剤としての1−シアノピロリジン誘導体 - Google Patents
Dub阻害剤としての1−シアノピロリジン誘導体 Download PDFInfo
- Publication number
- JP6959252B2 JP6959252B2 JP2018549534A JP2018549534A JP6959252B2 JP 6959252 B2 JP6959252 B2 JP 6959252B2 JP 2018549534 A JP2018549534 A JP 2018549534A JP 2018549534 A JP2018549534 A JP 2018549534A JP 6959252 B2 JP6959252 B2 JP 6959252B2
- Authority
- JP
- Japan
- Prior art keywords
- carbonitrile
- pyrrolidine
- oxadiazole
- pyrazole
- phenyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 0 C[C@@](CC1)C1N*(C)=*(C)C* Chemical compound C[C@@](CC1)C1N*(C)=*(C)C* 0.000 description 15
- BILISHPGOYUVSC-UHFFFAOYSA-N Bc(nc1OC)ccc1-[n]1cnc(C)c1 Chemical compound Bc(nc1OC)ccc1-[n]1cnc(C)c1 BILISHPGOYUVSC-UHFFFAOYSA-N 0.000 description 1
- NOGAAFSXFIEXQA-UHFFFAOYSA-N CC(CN(C=O)c(ccc(Br)n1)c1OC)=O Chemical compound CC(CN(C=O)c(ccc(Br)n1)c1OC)=O NOGAAFSXFIEXQA-UHFFFAOYSA-N 0.000 description 1
- HSVYYOLSYNEVSP-UHFFFAOYSA-N COc(nc(cc1)Br)c1N Chemical compound COc(nc(cc1)Br)c1N HSVYYOLSYNEVSP-UHFFFAOYSA-N 0.000 description 1
- PVISZDJJFXZAER-UHFFFAOYSA-O N#CCC(C1CC(CCC(OCc2ccccc2)=[OH+])CC1)=O Chemical compound N#CCC(C1CC(CCC(OCc2ccccc2)=[OH+])CC1)=O PVISZDJJFXZAER-UHFFFAOYSA-O 0.000 description 1
- VJXXMRABABKBBD-ZDUSSCGKSA-N N#Cc1c[n](-c2cc(-c3nc([C@H](CCC4)N4C#N)n[o]3)ccn2)nc1 Chemical compound N#Cc1c[n](-c2cc(-c3nc([C@H](CCC4)N4C#N)n[o]3)ccn2)nc1 VJXXMRABABKBBD-ZDUSSCGKSA-N 0.000 description 1
- VBDICJXDNUCWNB-UHFFFAOYSA-N OB(C(C=CC1)=CC1Br)O Chemical compound OB(C(C=CC1)=CC1Br)O VBDICJXDNUCWNB-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular 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
- C07D403/04—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 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
- C07D403/14—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 three or more hetero 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
- C07D413/04—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
-
- 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
- C07D417/14—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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Transplantation (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1605059.3 | 2016-03-24 | ||
| GBGB1605059.3A GB201605059D0 (en) | 2016-03-24 | 2016-03-24 | Novel compounds |
| GBGB1700839.2A GB201700839D0 (en) | 2017-01-18 | 2017-01-18 | Novel compounds |
| GB1700839.2 | 2017-01-18 | ||
| PCT/GB2017/050830 WO2017163078A1 (en) | 2016-03-24 | 2017-03-23 | 1-cyano-pyrrolidine derivatives as dbu inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019513135A JP2019513135A (ja) | 2019-05-23 |
| JP2019513135A5 JP2019513135A5 (https=) | 2020-02-27 |
| JP6959252B2 true JP6959252B2 (ja) | 2021-11-02 |
Family
ID=58455357
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018549534A Active JP6959252B2 (ja) | 2016-03-24 | 2017-03-23 | Dub阻害剤としての1−シアノピロリジン誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US11352339B2 (https=) |
| EP (1) | EP3433246B1 (https=) |
| JP (1) | JP6959252B2 (https=) |
| CN (1) | CN108884068B (https=) |
| MA (1) | MA43753A (https=) |
| WO (1) | WO2017163078A1 (https=) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX373656B (es) | 2015-03-30 | 2020-04-02 | Mission Therapeutics Ltd | Compuestos de 1-ciano-pirrolidina como inhibidores de las enzimas desubiquitinantes, como la hidrolasa 30 de la c-terminal de la ubiquitina (usp30), y el uso de los mismos en el tratamiento de condiciones de disfunción mitocondrial y tratamiento de cancér. |
| US10669234B2 (en) | 2015-07-14 | 2020-06-02 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
| GB201521109D0 (en) | 2015-11-30 | 2016-01-13 | Mission Therapeutics Ltd | Novel compounds |
| GB201522267D0 (en) | 2015-12-17 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201522768D0 (en) | 2015-12-23 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201602854D0 (en) | 2016-02-18 | 2016-04-06 | Mission Therapeutics Ltd | Novel compounds |
| GB201603779D0 (en) | 2016-03-04 | 2016-04-20 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| ES2850349T3 (es) | 2016-09-27 | 2021-08-27 | Mission Therapeutics Ltd | Derivados de cianopirrolidina con actividad como inhibidores de USP30 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
| GB201708652D0 (en) | 2017-05-31 | 2017-07-12 | Mission Therapeutics Ltd | Novel compounds and uses |
| JP7208931B2 (ja) | 2017-06-20 | 2023-01-19 | ミッション セラピューティクス リミティド | Dub阻害剤としての活性をもつ置換シアノピロリジン類 |
| BR112020003725A2 (pt) | 2017-10-06 | 2020-11-03 | Forma Therapeutics, Inc. | inibição da peptidase 30 específica de ubiquitina |
| GB2571731A (en) * | 2018-03-06 | 2019-09-11 | Mission Therapeutics Ltd | Novel compounds and uses |
| JP7449242B2 (ja) | 2018-05-17 | 2024-03-13 | フォーマ セラピューティクス,インコーポレイテッド | ユビキチン特異的ペプチダーゼ30(usp30)阻害剤として有用な縮合二環化合物 |
| JP7434285B2 (ja) * | 2018-08-14 | 2024-02-20 | アムジエン・インコーポレーテツド | N-シアノ-7-アザノルボルナン誘導体及びその使用 |
| LT3860989T (lt) * | 2018-10-05 | 2023-06-12 | Forma Therapeutics, Inc. | Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai |
| CN120698983A (zh) | 2018-12-20 | 2025-09-26 | C4医药公司 | 靶向蛋白降解 |
| GB201905371D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201905375D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| WO2021007477A1 (en) | 2019-07-11 | 2021-01-14 | E-Scape Bio, Inc. | Indazoles and azaindazoles as lrrk2 inhibitors |
| GB201912674D0 (en) | 2019-09-04 | 2019-10-16 | Mission Therapeutics Ltd | Novel compounds |
| WO2021204856A1 (en) * | 2020-04-08 | 2021-10-14 | Mission Therapeutics Limited | N-cyanopyrrolidines with activity as usp30 inhibitors |
| IL298526A (en) | 2020-05-28 | 2023-01-01 | Mission Therapeutics Ltd | N-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide derivatives and the corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction |
| BR112022019722A2 (pt) | 2020-06-04 | 2022-12-20 | Mission Therapeutics Ltd | N-cianopirrolidinas com atividade como inibidores de usp30 |
| DK4161929T3 (da) * | 2020-06-08 | 2025-08-18 | Mission Therapeutics Ltd | 1-(5-(2-cyanopyridin-4-yl)oxazol-2-carbonyl)-4-methylhexahydropyrrolo[3,4-b]pyrrol-5(1h)-carbonitril som usp30-hæmmer til anvendelse i behandling af mitokondriedysfunktion, cancer og fibrose |
| GB202016800D0 (en) | 2020-10-22 | 2020-12-09 | Mission Therapeutics Ltd | Novel compounds |
| US20250034122A1 (en) | 2021-12-01 | 2025-01-30 | Mission Therapeutics Limited | Substituted n-cyanopyrrolidines with activity as usp30 inhibitors |
| CN114646700B (zh) * | 2022-03-01 | 2023-10-20 | 浙江国邦药业有限公司 | 一种(s)-吡咯烷-2-甲腈盐酸盐的检测方法 |
| GB202408928D0 (en) | 2024-06-21 | 2024-08-07 | Mission Therapeutics Ltd | Novel compounds |
| GB202411060D0 (en) | 2024-07-29 | 2024-09-11 | Mission Therapeutics Ltd | Novel compounds |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5665754A (en) | 1993-09-20 | 1997-09-09 | Glaxo Wellcome Inc. | Substituted pyrrolidines |
| WO2001077073A1 (en) | 2000-04-06 | 2001-10-18 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
| RU2662443C2 (ru) | 2011-11-01 | 2018-07-26 | Ф. Хоффманн-Ля Рош Аг | Имидазопиридазины |
| JP6178861B2 (ja) | 2012-11-02 | 2017-08-09 | ファイザー・インク | ブルトン型チロシンキナーゼ阻害剤 |
| GB201309085D0 (en) | 2013-05-20 | 2013-07-03 | Redx Pharma Ltd | Compounds |
| CA2918242C (en) | 2013-07-31 | 2022-06-21 | Merck Patent Gmbh | Pyridines, pyrimidines, and pyrazines, as btk inhibitors and uses thereof |
| BR112016008632A8 (pt) * | 2013-10-21 | 2020-03-17 | Merck Patent Gmbh | compostos de heteroarila como inibidores de btk, seus usos, e composição farmacêutica |
| GB201404987D0 (en) | 2014-03-20 | 2014-05-07 | Redx Pharma Ltd | Compounds |
| WO2015157955A1 (en) | 2014-04-17 | 2015-10-22 | Abbvie Inc. | Heterocyclic btk inhibit ors |
| CN105017256A (zh) | 2014-04-29 | 2015-11-04 | 浙江导明医药科技有限公司 | 多氟化合物作为布鲁顿酪氨酸激酶抑制剂 |
| WO2016019237A2 (en) * | 2014-07-31 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| GB201416754D0 (en) | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| EA034931B1 (ru) | 2014-10-24 | 2020-04-08 | Бристол-Майерс Сквибб Компани | Индолкарбоксамидные соединения |
| MX373656B (es) * | 2015-03-30 | 2020-04-02 | Mission Therapeutics Ltd | Compuestos de 1-ciano-pirrolidina como inhibidores de las enzimas desubiquitinantes, como la hidrolasa 30 de la c-terminal de la ubiquitina (usp30), y el uso de los mismos en el tratamiento de condiciones de disfunción mitocondrial y tratamiento de cancér. |
| WO2016192074A1 (en) | 2015-06-04 | 2016-12-08 | Merck Sharp & Dohme Corp. | Btk inhibitors |
| US10669234B2 (en) | 2015-07-14 | 2020-06-02 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
| GB201521109D0 (en) | 2015-11-30 | 2016-01-13 | Mission Therapeutics Ltd | Novel compounds |
| GB201522267D0 (en) | 2015-12-17 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201522768D0 (en) | 2015-12-23 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| US10570118B2 (en) * | 2016-01-13 | 2020-02-25 | Boehringer Ingelheim International Gmbh | Isoquinolones as BTK inhibitors |
| GB201602854D0 (en) | 2016-02-18 | 2016-04-06 | Mission Therapeutics Ltd | Novel compounds |
| GB201603779D0 (en) | 2016-03-04 | 2016-04-20 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| US11180489B2 (en) | 2016-03-30 | 2021-11-23 | U niversity of Virginia Patent Foundation | Sphingosine kinase inhibitor amidoxime prodrugs |
| CN107383013B (zh) | 2016-05-16 | 2020-03-31 | 苏州信诺维医药科技有限公司 | 作为btk抑制剂的吡唑并嘧啶衍生物及其制备方法和药物组合物 |
| AU2017265219B2 (en) | 2016-05-16 | 2021-02-04 | Evopoint Biosciences Co., Ltd. | 5-aminopyrazole carboxamide derivative as BTK inhibitor and preparation method and pharmaceutical composition thereof |
| ES2850349T3 (es) | 2016-09-27 | 2021-08-27 | Mission Therapeutics Ltd | Derivados de cianopirrolidina con actividad como inhibidores de USP30 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
-
2017
- 2017-03-23 JP JP2018549534A patent/JP6959252B2/ja active Active
- 2017-03-23 MA MA043753A patent/MA43753A/fr unknown
- 2017-03-23 US US16/087,515 patent/US11352339B2/en active Active
- 2017-03-23 EP EP17714540.6A patent/EP3433246B1/en active Active
- 2017-03-23 CN CN201780018998.XA patent/CN108884068B/zh active Active
- 2017-03-23 WO PCT/GB2017/050830 patent/WO2017163078A1/en not_active Ceased
-
2022
- 2022-02-18 US US17/674,943 patent/US11945797B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| MA43753A (fr) | 2018-11-28 |
| JP2019513135A (ja) | 2019-05-23 |
| US20200331888A1 (en) | 2020-10-22 |
| US11352339B2 (en) | 2022-06-07 |
| WO2017163078A1 (en) | 2017-09-28 |
| CN108884068A (zh) | 2018-11-23 |
| EP3433246A1 (en) | 2019-01-30 |
| US20220177451A1 (en) | 2022-06-09 |
| CN108884068B (zh) | 2021-02-26 |
| EP3433246B1 (en) | 2022-05-04 |
| US11945797B2 (en) | 2024-04-02 |
| WO2017163078A8 (en) | 2017-12-28 |
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