JP7035027B2 - Betタンパク質分解物質としての縮合1,4-ジアゼピン - Google Patents
Betタンパク質分解物質としての縮合1,4-ジアゼピン Download PDFInfo
- Publication number
- JP7035027B2 JP7035027B2 JP2019513958A JP2019513958A JP7035027B2 JP 7035027 B2 JP7035027 B2 JP 7035027B2 JP 2019513958 A JP2019513958 A JP 2019513958A JP 2019513958 A JP2019513958 A JP 2019513958A JP 7035027 B2 JP7035027 B2 JP 7035027B2
- Authority
- JP
- Japan
- Prior art keywords
- diazepine
- chlorophenyl
- ethynyl
- thieno
- triazolo
- 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.)
- Expired - Fee Related
Links
- 0 *C1=**=C2*1c([n]c(C#*)c1*)c1C(c1ccccc1)=*C2 Chemical compound *C1=**=C2*1c([n]c(C#*)c1*)c1C(c1ccccc1)=*C2 0.000 description 16
- VNOIIAHVJYKWCF-UHFFFAOYSA-N C#Cc1c[n](CCCC#Cc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)nn1 Chemical compound C#Cc1c[n](CCCC#Cc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)nn1 VNOIIAHVJYKWCF-UHFFFAOYSA-N 0.000 description 2
- RXYPXQSKLGGKOL-UHFFFAOYSA-N CN1CCN(C)CC1 Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
- BXMPTABHXKPFHQ-VIFPVBQESA-N C[C@@H](c1nnc(C)[n]1-c([s]1)c2c(C)c1I)N=C2c(cc1)ccc1Cl Chemical compound C[C@@H](c1nnc(C)[n]1-c([s]1)c2c(C)c1I)N=C2c(cc1)ccc1Cl BXMPTABHXKPFHQ-VIFPVBQESA-N 0.000 description 2
- PGMQRYZQVRHFSE-UHFFFAOYSA-N Cc(c(C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]1-1)c-1[s]1)c1I Chemical compound Cc(c(C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]1-1)c-1[s]1)c1I PGMQRYZQVRHFSE-UHFFFAOYSA-N 0.000 description 2
- NKCRVSLFDGZZEX-UHFFFAOYSA-N OCCCC#Cc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O Chemical compound OCCCC#Cc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O NKCRVSLFDGZZEX-UHFFFAOYSA-N 0.000 description 2
- BJXDBXQZKWQSBV-UHFFFAOYSA-N C#Cc1c[nH]cn1 Chemical compound C#Cc1c[nH]cn1 BJXDBXQZKWQSBV-UHFFFAOYSA-N 0.000 description 1
- ZBQYZDNVOUABIJ-UHFFFAOYSA-N C#Cc1ncc(CCCCNc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)cc1 Chemical compound C#Cc1ncc(CCCCNc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)cc1 ZBQYZDNVOUABIJ-UHFFFAOYSA-N 0.000 description 1
- RFMGNXYYTBOQAV-UHFFFAOYSA-N C#Cc1ncc(COCCCCc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)cc1 Chemical compound C#Cc1ncc(COCCCCc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)cc1 RFMGNXYYTBOQAV-UHFFFAOYSA-N 0.000 description 1
- QPRHXGPAGFNADJ-KRXBUXKQSA-N C/C=C(\C#Cc1c[nH]cn1)/S Chemical compound C/C=C(\C#Cc1c[nH]cn1)/S QPRHXGPAGFNADJ-KRXBUXKQSA-N 0.000 description 1
- ONPIRZWOLVCPGQ-UHFFFAOYSA-N CC(C(C=C1)C2=NCc3nnc(C)[n]3-c3c2c(C)c(C#Cc2c[n](CCCC#Cc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)cn2)[s]3)C=C1Cl Chemical compound CC(C(C=C1)C2=NCc3nnc(C)[n]3-c3c2c(C)c(C#Cc2c[n](CCCC#Cc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)cn2)[s]3)C=C1Cl ONPIRZWOLVCPGQ-UHFFFAOYSA-N 0.000 description 1
- IAJMOILSUIJSMI-UHFFFAOYSA-N CS(OCCCC#Cc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O)(=O)=O Chemical compound CS(OCCCC#Cc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O)(=O)=O IAJMOILSUIJSMI-UHFFFAOYSA-N 0.000 description 1
- ZAHJDBKKACFOQC-UHFFFAOYSA-N CS(OCCCCCc1c(CN(C(CCC(N2)=O)C2=O)C2=O)c2ccc1)(=O)=O Chemical compound CS(OCCCCCc1c(CN(C(CCC(N2)=O)C2=O)C2=O)c2ccc1)(=O)=O ZAHJDBKKACFOQC-UHFFFAOYSA-N 0.000 description 1
- YWNIISHGJPELBA-RUBXLXHKSA-N C[C@@H](c1nnc(C)[n]1-c1c2c(C)c(C#Cc3c[n](CCCCCc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)nc3)[s]1)N=C2c(cc1)ccc1Cl Chemical compound C[C@@H](c1nnc(C)[n]1-c1c2c(C)c(C#Cc3c[n](CCCCCc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)nc3)[s]1)N=C2c(cc1)ccc1Cl YWNIISHGJPELBA-RUBXLXHKSA-N 0.000 description 1
- MZJOVBREDPNNKF-PPVAYSNCSA-N C[C@@H](c1nnc(C)[n]1-c1c2c(C)c(C#Cc3cnc(CCCCNc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)cc3)[s]1)N=C2c(cc1)ccc1Cl Chemical compound C[C@@H](c1nnc(C)[n]1-c1c2c(C)c(C#Cc3cnc(CCCCNc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)cc3)[s]1)N=C2c(cc1)ccc1Cl MZJOVBREDPNNKF-PPVAYSNCSA-N 0.000 description 1
- FCOCTISPZQFCLQ-GWJDSUCGSA-N C[C@@H](c1nnc(C)[n]11)N=C(c(cc2)ccc2Cl)C(/C(/C)=C(\C)/C#Cc2c[n](CCCC#Cc3cccc4c3CN(C(CCC(N3)=O)C3=O)C4=O)nn2)=C1S Chemical compound C[C@@H](c1nnc(C)[n]11)N=C(c(cc2)ccc2Cl)C(/C(/C)=C(\C)/C#Cc2c[n](CCCC#Cc3cccc4c3CN(C(CCC(N3)=O)C3=O)C4=O)nn2)=C1S FCOCTISPZQFCLQ-GWJDSUCGSA-N 0.000 description 1
- PGYUBRMQDYIZFD-UHFFFAOYSA-N Cc1c(C#Cc2c[n](CCCC#C)cn2)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 Chemical compound Cc1c(C#Cc2c[n](CCCC#C)cn2)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 PGYUBRMQDYIZFD-UHFFFAOYSA-N 0.000 description 1
- FTOKUERYAJMQJF-UHFFFAOYSA-N Cc1c(C#Cc2c[n](CCCCCc3cccc4c3CN(C(CCC(N3)=O)C3=O)C4=O)nn2)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 Chemical compound Cc1c(C#Cc2c[n](CCCCCc3cccc4c3CN(C(CCC(N3)=O)C3=O)C4=O)nn2)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 FTOKUERYAJMQJF-UHFFFAOYSA-N 0.000 description 1
- GFUYCZDCAQCDGA-UHFFFAOYSA-N Cc1c(C#Cc2cnc[n]2CCCC#C)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 Chemical compound Cc1c(C#Cc2cnc[n]2CCCC#C)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 GFUYCZDCAQCDGA-UHFFFAOYSA-N 0.000 description 1
- PAZUSKGTBLWJAI-UHFFFAOYSA-N Cc1c[n](CCCCN)[n]c1 Chemical compound Cc1c[n](CCCCN)[n]c1 PAZUSKGTBLWJAI-UHFFFAOYSA-N 0.000 description 1
- MYGYXFCDNNRSJM-UHFFFAOYSA-N Cc1c[s]c(N)c1C(c1ccc(C)cc1)=O Chemical compound Cc1c[s]c(N)c1C(c1ccc(C)cc1)=O MYGYXFCDNNRSJM-UHFFFAOYSA-N 0.000 description 1
- URLKBWYHVLBVBO-UHFFFAOYSA-N Cc1ccc(C)cc1 Chemical compound Cc1ccc(C)cc1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 1
- RHOOLJLEYYXKTK-UHFFFAOYSA-N Cc1cnc(C)nc1 Chemical compound Cc1cnc(C)nc1 RHOOLJLEYYXKTK-UHFFFAOYSA-N 0.000 description 1
- LHMZYMGVGMFPFJ-UHFFFAOYSA-N Cc1nnc(CNC)[nH]1 Chemical compound Cc1nnc(CNC)[nH]1 LHMZYMGVGMFPFJ-UHFFFAOYSA-N 0.000 description 1
- UNJJNIWGIYMKDN-UHFFFAOYSA-N NC(C=CC1)=C(CN2C(CCC(N3)=O)C3=O)C1C2=O Chemical compound NC(C=CC1)=C(CN2C(CCC(N3)=O)C3=O)C1C2=O UNJJNIWGIYMKDN-UHFFFAOYSA-N 0.000 description 1
- SCZFMUWTABGOGF-UHFFFAOYSA-N O=C(c1c(C2)c(Br)ccc1)N2C(CCC(N1)=O)C1=O Chemical compound O=C(c1c(C2)c(Br)ccc1)N2C(CCC(N1)=O)C1=O SCZFMUWTABGOGF-UHFFFAOYSA-N 0.000 description 1
- VROGWIJGMISOHP-UHFFFAOYSA-N OCCCCCc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O Chemical compound OCCCCCc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O VROGWIJGMISOHP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed 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
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662393923P | 2016-09-13 | 2016-09-13 | |
| US62/393,923 | 2016-09-13 | ||
| PCT/US2017/051286 WO2018052949A1 (en) | 2016-09-13 | 2017-09-13 | Fused 1,4-diazepines as bet protein degraders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019526616A JP2019526616A (ja) | 2019-09-19 |
| JP2019526616A5 JP2019526616A5 (enExample) | 2020-10-22 |
| JP7035027B2 true JP7035027B2 (ja) | 2022-03-14 |
Family
ID=60002003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019513958A Expired - Fee Related JP7035027B2 (ja) | 2016-09-13 | 2017-09-13 | Betタンパク質分解物質としての縮合1,4-ジアゼピン |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US10975093B2 (enExample) |
| EP (2) | EP3858837A1 (enExample) |
| JP (1) | JP7035027B2 (enExample) |
| CN (1) | CN110072866A (enExample) |
| AU (1) | AU2017326175B2 (enExample) |
| CA (1) | CA3036841A1 (enExample) |
| ES (1) | ES2857743T3 (enExample) |
| WO (1) | WO2018052949A1 (enExample) |
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|---|---|---|---|---|
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| EP3455219A4 (en) | 2016-05-10 | 2019-12-18 | C4 Therapeutics, Inc. | AMINE-RELATED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN REDUCTION |
| WO2017197046A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | C3-carbon linked glutarimide degronimers for target protein degradation |
| WO2017197055A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| EP3454862B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| US11046709B2 (en) * | 2017-02-03 | 2021-06-29 | The Regents Of The University Of Michigan | Fused 1,4-diazepines as BET bromodomain inhibitors |
| CN110769822A (zh) | 2017-06-20 | 2020-02-07 | C4医药公司 | 用于蛋白降解的n/o-连接的降解决定子和降解决定子体 |
| WO2019043217A1 (en) | 2017-09-04 | 2019-03-07 | F. Hoffmann-La Roche Ag | DIHYDROBENZIMIDAZOLONES |
| WO2019043208A1 (en) | 2017-09-04 | 2019-03-07 | F. Hoffmann-La Roche Ag | DIHYDROQUINOLINONES |
| WO2019043214A1 (en) | 2017-09-04 | 2019-03-07 | F. Hoffmann-La Roche Ag | glutarimide |
| CN111372585A (zh) | 2017-11-16 | 2020-07-03 | C4医药公司 | 用于靶蛋白降解的降解剂和降解决定子 |
| KR20210018199A (ko) | 2018-03-26 | 2021-02-17 | 씨4 테라퓨틱스, 인코포레이티드 | 이카로스의 분해를 위한 세레블론 결합제 |
| JP7367908B2 (ja) * | 2018-04-09 | 2023-10-24 | 上海科技大学 | 標的タンパク質分解化合物、その抗腫瘍応用、その中間体および中間体の応用 |
| JP2021521192A (ja) * | 2018-04-13 | 2021-08-26 | アルビナス・オペレーションズ・インコーポレイテッドArvinas Operations, Inc. | セレブロンリガンドおよび同リガンドを含む二機能性化合物 |
| WO2019204354A1 (en) | 2018-04-16 | 2019-10-24 | C4 Therapeutics, Inc. | Spirocyclic compounds |
| AU2019261938B2 (en) * | 2018-04-30 | 2024-06-13 | Dana-Farber Cancer Institute, Inc. | Small molecule degraders of polybromo-1 (PBRM1) |
| EP3578561A1 (en) | 2018-06-04 | 2019-12-11 | F. Hoffmann-La Roche AG | Spiro compounds |
| WO2020009176A1 (ja) * | 2018-07-04 | 2020-01-09 | 田辺三菱製薬株式会社 | Bet蛋白質分解誘導作用を有するアミド化合物及びその医薬としての用途 |
| CN110407854B (zh) * | 2018-08-17 | 2020-09-15 | 北京加科思新药研发有限公司 | 新的四环化合物 |
| EP3841100A1 (en) | 2018-08-20 | 2021-06-30 | Arvinas Operations, Inc. | Proteolysis targeting chimeric (protac) compound with e3 ubiquitin ligase binding activity and targeting alpha-synuclein protein for treating neurodegenerative diseases |
| US11969472B2 (en) | 2018-08-22 | 2024-04-30 | Cullgen (Shanghai), Inc. | Tropomyosin receptor kinase (TRK) degradation compounds and methods of use |
| EP3841098A4 (en) | 2018-08-22 | 2022-05-04 | Cullgen (Shanghai), Inc. | TROPOMYOSIN RECEPTOR KINASE (TRK) DEGRADATION COMPOUNDS AND METHOD OF USE |
| CA3119343C (en) | 2018-11-13 | 2024-01-16 | Biotheryx, Inc. | Substituted isoindolinones |
| CN113453679B (zh) | 2018-12-20 | 2025-07-08 | C4医药公司 | 靶向蛋白降解 |
| JP7548992B2 (ja) | 2019-07-17 | 2024-09-10 | アルビナス・オペレーションズ・インコーポレイテッド | タウタンパク質標的化化合物および関連する使用方法 |
| MX2022004526A (es) | 2019-10-17 | 2022-07-21 | Arvinas Operations Inc | Moléculas bifuncionales que contienen una porción de unión a la ligasa de ubiquitina e3 unida a una porción de direccionamiento a bcl6. |
| JP2023508891A (ja) * | 2019-12-17 | 2023-03-06 | オリオニス バイオサイエンシズ,インコーポレイテッド | タンパク質の動員および/または分解のための二機能性剤 |
| WO2023205701A1 (en) | 2022-04-20 | 2023-10-26 | Kumquat Biosciences Inc. | Macrocyclic heterocycles and uses thereof |
| CN115697989B (zh) | 2020-02-26 | 2025-03-18 | 上海睿跃生物科技有限公司 | 原肌球蛋白受体激酶(trk)降解化合物和使用方法 |
| EP4114392A4 (en) | 2020-03-05 | 2024-04-10 | C4 Therapeutics, Inc. | Compounds for targeted degradation of brd9 |
| JP2023539663A (ja) | 2020-08-28 | 2023-09-15 | アルビナス・オペレーションズ・インコーポレイテッド | 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法 |
| JP2024504932A (ja) | 2021-01-13 | 2024-02-02 | モンテ ローザ セラピューティクス, インコーポレイテッド | イソインドリノン化合物 |
| CN116802180B (zh) * | 2021-01-22 | 2024-05-28 | 泰比棣医药科技(石家庄)有限公司 | 一种降解脱氧核糖核酸(dna)聚合酶的化合物及其用途 |
| JP2024515619A (ja) | 2021-04-16 | 2024-04-10 | アルビナス・オペレーションズ・インコーポレイテッド | Bcl6タンパク質分解の調節因子および関連する使用方法 |
| JP2024529298A (ja) | 2021-07-09 | 2024-08-06 | プレキシウム インコーポレイテッド | Ikzf2を調節するアリール化合物及び医薬組成物 |
| CN115611881B (zh) * | 2021-07-13 | 2024-09-20 | 复旦大学 | 一种合成新型vhl配体4-f-vh032的方法 |
| WO2023074780A1 (ja) * | 2021-10-27 | 2023-05-04 | 国立大学法人愛媛大学 | 治療薬組成物 |
| EP4584258A1 (en) | 2022-09-07 | 2025-07-16 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
| CN116585322B (zh) * | 2023-01-16 | 2023-10-13 | 中山大学中山眼科中心 | Bet蛋白降解剂在预防和治疗视网膜退行性改变相关疾病中的应用 |
| AU2024276994A1 (en) | 2023-05-24 | 2025-10-23 | Kumquat Biosciences Inc. | Heterocyclic compounds and uses thereof |
| TW202502779A (zh) | 2023-06-30 | 2025-01-16 | 美商金橘生物科技公司 | 取代的雜芳族胺及其用途 |
| WO2025011624A1 (en) * | 2023-07-11 | 2025-01-16 | Etern Biopharma (Shanghai) Co., Ltd. | Bifunctional compounds for androgen receptor degradation and methods of use |
| WO2025096855A1 (en) | 2023-11-02 | 2025-05-08 | Kumquat Biosciences Inc. | Degraders and uses thereof |
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| US20220356192A1 (en) | 2022-11-10 |
| EP3512853A1 (en) | 2019-07-24 |
| AU2017326175B2 (en) | 2022-01-27 |
| CN110072866A (zh) | 2019-07-30 |
| US10975093B2 (en) | 2021-04-13 |
| CA3036841A1 (en) | 2018-03-22 |
| ES2857743T3 (es) | 2021-09-29 |
| EP3512853B1 (en) | 2020-12-23 |
| WO2018052949A1 (en) | 2018-03-22 |
| AU2017326175A1 (en) | 2019-04-04 |
| EP3858837A1 (en) | 2021-08-04 |
| JP2019526616A (ja) | 2019-09-19 |
| US20190263827A1 (en) | 2019-08-29 |
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