JPWO2020094104A5 - - Google Patents
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- JPWO2020094104A5 JPWO2020094104A5 JP2021524993A JP2021524993A JPWO2020094104A5 JP WO2020094104 A5 JPWO2020094104 A5 JP WO2020094104A5 JP 2021524993 A JP2021524993 A JP 2021524993A JP 2021524993 A JP2021524993 A JP 2021524993A JP WO2020094104 A5 JPWO2020094104 A5 JP WO2020094104A5
- Authority
- JP
- Japan
- Prior art keywords
- group
- membered
- ring
- alkyl
- heterocycloalkyl
- 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.)
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- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 101
- 125000000217 alkyl group Chemical group 0.000 claims 78
- 125000000753 cycloalkyl group Chemical group 0.000 claims 71
- 125000004435 hydrogen atoms Chemical class [H]* 0.000 claims 66
- 125000003118 aryl group Chemical group 0.000 claims 62
- 125000002950 monocyclic group Chemical group 0.000 claims 59
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 56
- 229910052736 halogen Inorganic materials 0.000 claims 54
- 150000002367 halogens Chemical class 0.000 claims 54
- 125000003277 amino group Chemical group 0.000 claims 47
- 125000001424 substituent group Chemical group 0.000 claims 36
- 125000003545 alkoxy group Chemical group 0.000 claims 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 35
- 229910052739 hydrogen Inorganic materials 0.000 claims 33
- 239000001257 hydrogen Substances 0.000 claims 33
- 125000001072 heteroaryl group Chemical group 0.000 claims 31
- 125000004429 atoms Chemical group 0.000 claims 28
- 125000003367 polycyclic group Chemical group 0.000 claims 23
- 150000001875 compounds Chemical class 0.000 claims 22
- 125000003003 spiro group Chemical group 0.000 claims 21
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 20
- 125000005842 heteroatoms Chemical group 0.000 claims 19
- 150000002391 heterocyclic compounds Chemical class 0.000 claims 19
- 229910052757 nitrogen Inorganic materials 0.000 claims 18
- 125000004432 carbon atoms Chemical group C* 0.000 claims 16
- 229910052760 oxygen Inorganic materials 0.000 claims 15
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 14
- 125000004122 cyclic group Chemical group 0.000 claims 14
- 150000003839 salts Chemical class 0.000 claims 13
- 239000011780 sodium chloride Substances 0.000 claims 13
- 239000012453 solvate Substances 0.000 claims 13
- 239000000651 prodrug Substances 0.000 claims 12
- 229940002612 prodrugs Drugs 0.000 claims 12
- 229910052717 sulfur Inorganic materials 0.000 claims 12
- 125000003342 alkenyl group Chemical group 0.000 claims 11
- 125000000304 alkynyl group Chemical group 0.000 claims 11
- 229910052698 phosphorus Inorganic materials 0.000 claims 11
- YZCKVEUIGOORGS-OUBTZVSYSA-N deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 10
- 229910052805 deuterium Inorganic materials 0.000 claims 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 8
- 229910052731 fluorine Inorganic materials 0.000 claims 8
- 201000005202 lung cancer Diseases 0.000 claims 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 8
- 125000003282 alkyl amino group Chemical group 0.000 claims 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims 7
- 125000000623 heterocyclic group Chemical group 0.000 claims 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 6
- -1 hydroxy, amino Chemical group 0.000 claims 6
- 229910052794 bromium Inorganic materials 0.000 claims 5
- 229910052801 chlorine Inorganic materials 0.000 claims 5
- 229910052740 iodine Inorganic materials 0.000 claims 5
- 125000002252 acyl group Chemical group 0.000 claims 4
- 125000003368 amide group Chemical group 0.000 claims 4
- 239000004202 carbamide Substances 0.000 claims 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 125000004433 nitrogen atoms Chemical group N* 0.000 claims 4
- 238000006467 substitution reaction Methods 0.000 claims 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 4
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 3
- 206010017758 Gastric cancer Diseases 0.000 claims 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 3
- 125000005256 alkoxyacyl group Chemical group 0.000 claims 3
- 125000000033 alkoxyamino group Chemical group 0.000 claims 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 3
- 125000005418 aryl aryl group Chemical group 0.000 claims 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 3
- 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 claims 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 3
- ZEJHEROGFWIRLO-UHFFFAOYSA-N nitrosulfonylformonitrile Chemical compound [O-][N+](=O)S(=O)(=O)C#N ZEJHEROGFWIRLO-UHFFFAOYSA-N 0.000 claims 3
- 239000001301 oxygen Substances 0.000 claims 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 201000011549 stomach cancer Diseases 0.000 claims 3
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 3
- 125000003375 sulfoxide group Chemical group 0.000 claims 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 102100007290 CD274 Human genes 0.000 claims 2
- 101710012053 CD274 Proteins 0.000 claims 2
- 206010024324 Leukaemias Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 2
- 239000012270 PD-1 inhibitor Substances 0.000 claims 2
- 229940121655 PD-1 inhibitors Drugs 0.000 claims 2
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 201000011231 colorectal cancer Diseases 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229940079593 drugs Drugs 0.000 claims 2
- 201000004101 esophageal cancer Diseases 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000000565 sulfonamide group Chemical group 0.000 claims 2
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims 2
- 125000004434 sulfur atoms Chemical group 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- 102100019764 PDCD1 Human genes 0.000 claims 1
- 102100017818 PTPN11 Human genes 0.000 claims 1
- 101710018405 PTPN11 Proteins 0.000 claims 1
- 108060007796 SPATA2 Proteins 0.000 claims 1
- 229940090121 Sulfonylureas for blood glucose lowering Drugs 0.000 claims 1
- 101700028234 agl5 Proteins 0.000 claims 1
- 102000004965 antibodies Human genes 0.000 claims 1
- 108090001123 antibodies Proteins 0.000 claims 1
- 125000006165 cyclic alkyl group Chemical group 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 230000004952 protein activity Effects 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 230000019491 signal transduction Effects 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811317588 | 2018-11-07 | ||
| CN201811317588.8 | 2018-11-07 | ||
| CN201811594644 | 2018-12-26 | ||
| CN201811594644.2 | 2018-12-26 | ||
| CN201910131491.6 | 2019-02-22 | ||
| CN201910131491 | 2019-02-22 | ||
| PCT/CN2019/116386 WO2020094104A1 (zh) | 2018-11-07 | 2019-11-07 | 一类含氮稠杂环类shp2抑制剂化合物、制备方法和用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2022506887A JP2022506887A (ja) | 2022-01-17 |
| JPWO2020094104A5 true JPWO2020094104A5 (pt) | 2022-09-01 |
Family
ID=70556058
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021524993A Pending JP2022506887A (ja) | 2018-11-07 | 2019-11-07 | 窒素含有縮合複素環系ｓｈｐ２阻害剤化合物、製造方法及び使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20220127271A1 (pt) |
| EP (1) | EP3878853A4 (pt) |
| JP (1) | JP2022506887A (pt) |
| KR (1) | KR20210089716A (pt) |
| CN (2) | CN111153901B (pt) |
| WO (1) | WO2020094104A1 (pt) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018057884A1 (en) | 2016-09-22 | 2018-03-29 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
| TW201819386A (zh) | 2016-10-24 | 2018-06-01 | 美商傳達治療有限公司 | Shp2磷酸酶抑制劑及其使用方法 |
| IL296456A (en) | 2017-01-23 | 2022-11-01 | Revolution Medicines Inc | Bicyclics as allosteric shp2 inhibitors |
| BR112019014527A2 (pt) | 2017-01-23 | 2020-02-27 | Revolution Medicines, Inc. | Compostos de piridina como inibidores de shp2 alostéricos |
| EP3630770A1 (en) | 2017-05-26 | 2020-04-08 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors |
| AU2018328273A1 (en) | 2017-09-07 | 2020-03-12 | Revolution Medicines, Inc. | SHP2 inhibitor compositions and methods for treating cancer |
| US11701354B2 (en) | 2017-09-29 | 2023-07-18 | D. E. Shaw Research, Llc | Pyrazolo[3,4-b]pyrazine derivatives as SHP2 phosphatase inhibitors |
| AU2018347516A1 (en) | 2017-10-12 | 2020-05-07 | Revolution Medicines, Inc. | Pyridine, pyrazine, and triazine compounds as allosteric SHP2 inhibitors |
| SG11202004090YA (en) * | 2017-12-15 | 2020-05-28 | Revolution Medicines Inc | Polycyclic compounds as allosteric shp2 inhibitors |
| TW202003471A (zh) | 2018-03-21 | 2020-01-16 | 美商傳達治療有限公司 | Shp2磷酸酶抑制劑及其使用方法 |
| WO2020072656A1 (en) | 2018-10-03 | 2020-04-09 | Gilead Sciences, Inc. | Imidozopyrimidine derivatives |
| CN117143079A (zh) | 2018-11-06 | 2023-12-01 | 上海奕拓医药科技有限责任公司 | 一种螺芳环化合物及其应用 |
| US20220380385A1 (en) * | 2019-06-28 | 2022-12-01 | Tuojie Biotech(Shanghai) Co., Ltd. | Pyrimidine five-membered nitrogen heterocyclic derivative, preparation method thereof and pharmaceutical use thereof |
| CN111704611B (zh) * | 2019-07-25 | 2022-01-14 | 上海凌达生物医药有限公司 | 一类芳基螺环类shp2抑制剂化合物、制备方法和用途 |
| CN112300160A (zh) * | 2019-08-01 | 2021-02-02 | 上海奕拓医药科技有限责任公司 | 一种螺芳环化合物、其制备及应用 |
| EP3772513A1 (en) | 2019-08-09 | 2021-02-10 | C.N.C.C.S. S.c.a.r.l. Collezione Nazionale Dei Composti Chimici e Centro Screening | Shp2 inhibitors |
| US11890281B2 (en) | 2019-09-24 | 2024-02-06 | Relay Therapeutics, Inc. | SHP2 phosphatase inhibitors and methods of making and using the same |
| EP4056563A4 (en) * | 2019-11-08 | 2024-02-21 | Nanjing Sanhome Pharmaceutical Co Ltd | COMPOUND USED AS SHP2 INHIBITOR AND ITS USE |
| CN113754683A (zh) * | 2020-06-05 | 2021-12-07 | 上海奕拓医药科技有限责任公司 | 同位素取代的螺芳环化合物及其应用 |
| KR20230026458A (ko) * | 2020-06-18 | 2023-02-24 | 이턴 바이오파마 (상하이) 코., 엘티디. | Shp2 억제제의 결정형 및 이의 조성물, 제조 방법과 용도 |
| WO2021257736A1 (en) | 2020-06-18 | 2021-12-23 | Revolution Medicines, Inc. | Methods for delaying, preventing, and treating acquired resistance to ras inhibitors |
| IL301062A (en) | 2020-09-03 | 2023-05-01 | Revolution Medicines Inc | Use of SOS1 inhibitors to treat malignancies with SHP2 mutations |
| PE20231207A1 (es) | 2020-09-15 | 2023-08-17 | Revolution Medicines Inc | Derivados indolicos como inhibidores de ras en el tratamiento del cancer |
| CN114437116A (zh) * | 2020-10-30 | 2022-05-06 | 赣江新区博瑞创新医药有限公司 | 杂环化合物及其制备方法、药物组合物和应用 |
| WO2022135568A1 (zh) * | 2020-12-25 | 2022-06-30 | 江苏恒瑞医药股份有限公司 | 一种嘧啶并五元氮杂环类衍生物的晶型及其制备方法 |
| MX2023009190A (es) * | 2021-02-05 | 2023-08-21 | Hutchmed Ltd | Compuestos triciclicos y usos de los mismos. |
| CN117500811A (zh) | 2021-05-05 | 2024-02-02 | 锐新医药公司 | 共价ras抑制剂及其用途 |
| WO2022235864A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2022235870A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Ras inhibitors for the treatment of cancer |
| TW202313041A (zh) | 2021-06-09 | 2023-04-01 | 瑞士商諾華公司 | 包含達拉菲尼、曲美替尼和shp2抑制劑之三重藥物組合 |
| TW202317100A (zh) | 2021-06-23 | 2023-05-01 | 瑞士商諾華公司 | 包含ｋｒａｓ ｇ１２ｃ抑制劑的藥物組合及其用於治療癌症之用途 |
| WO2023025290A1 (zh) * | 2021-08-27 | 2023-03-02 | 江苏恒瑞医药股份有限公司 | Shp2抑制剂治疗含有ras通路基因突变的肿瘤的用途 |
| WO2023031781A1 (en) | 2021-09-01 | 2023-03-09 | Novartis Ag | Pharmaceutical combinations comprising a tead inhibitor and uses thereof for the treatment of cancers |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| EP4227307A1 (en) * | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
| WO2023220703A1 (en) * | 2022-05-12 | 2023-11-16 | Genentech, Inc. | Methods and compositions comprising a shp2 inhibitor and a pd-l1 binding antagonist |
| CN114920759A (zh) * | 2022-05-18 | 2022-08-19 | 江南大学 | 杂环-三氮唑并噻二唑杂环串联化合物、合成方法、药物组合物及用途 |
| WO2023230968A1 (zh) * | 2022-06-01 | 2023-12-07 | 上海凌达生物医药有限公司 | Shp2抑制剂、其晶型及其制备方法与用途 |
| WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201200518A (en) * | 2010-03-10 | 2012-01-01 | Kalypsys Inc | Heterocyclic inhibitors of histamine receptors for the treatment of disease |
| CN104640863B (zh) * | 2012-09-20 | 2016-06-08 | 山东亨利医药科技有限责任公司 | 嘧啶胺衍生物及其制备方法和应用 |
| US10093646B2 (en) * | 2014-01-17 | 2018-10-09 | Novartis Ag | 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2 |
| MX2017012699A (es) * | 2015-04-03 | 2018-02-09 | Incyte Corp | Compuestos heterociclicos como inhibidores de demetilasa 1 especifica de lisina (lsd1). |
| IL296456A (en) * | 2017-01-23 | 2022-11-01 | Revolution Medicines Inc | Bicyclics as allosteric shp2 inhibitors |
| JP6878615B2 (ja) | 2017-03-23 | 2021-05-26 | ジャコバイオ ファーマスーティカルズ カンパニー リミテッドＪａｃｏｂｉｏ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｃｏ．， Ｌｔｄ． | Ｓｈｐ２阻害剤として有用な新規な複素環式誘導体 |
| SG11202004090YA (en) * | 2017-12-15 | 2020-05-28 | Revolution Medicines Inc | Polycyclic compounds as allosteric shp2 inhibitors |
| CN110156786B (zh) * | 2018-02-13 | 2022-06-03 | 青煜医药研发(上海)有限公司 | 嘧啶并环化合物及其制备方法和应用 |
| SG11202007740TA (en) * | 2018-02-13 | 2020-09-29 | Shanghai Blueray Biopharma Co Ltd | Pyrimidine-fused cyclic compound, preparation method therefor and application thereof |
| CN110655520A (zh) * | 2018-06-29 | 2020-01-07 | 上海青煜医药科技有限公司 | 嘧啶并环化合物及其制备方法和应用 |
| US20210393623A1 (en) * | 2018-09-26 | 2021-12-23 | Jacobio Pharmaceuticals Co., Ltd. | Novel Heterocyclic Derivatives Useful as SHP2 Inhibitors |
| WO2020072656A1 (en) * | 2018-10-03 | 2020-04-09 | Gilead Sciences, Inc. | Imidozopyrimidine derivatives |
| CN117143079A (zh) * | 2018-11-06 | 2023-12-01 | 上海奕拓医药科技有限责任公司 | 一种螺芳环化合物及其应用 |
| BR112021009880A2 (pt) * | 2018-11-30 | 2021-08-17 | Tuojie Biotech (Shanghai) Co., Ltd. | pirimidina e derivado de heterociclo de nitrogênio de cinco membros, método de preparação para os mesmos e usos médicos dos mesmos |
-
2019
- 2019-11-07 US US17/292,027 patent/US20220127271A1/en active Pending
- 2019-11-07 EP EP19882124.1A patent/EP3878853A4/en active Pending
- 2019-11-07 KR KR1020217017327A patent/KR20210089716A/ko active Search and Examination
- 2019-11-07 JP JP2021524993A patent/JP2022506887A/ja active Pending
- 2019-11-07 CN CN201911083409.3A patent/CN111153901B/zh active Active
- 2019-11-07 WO PCT/CN2019/116386 patent/WO2020094104A1/zh unknown
- 2019-11-07 CN CN202210220952.9A patent/CN114751903B/zh active Active
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