ES2821877T3 - Espirolactamas como inhibidores de ROCK - Google Patents
Espirolactamas como inhibidores de ROCK Download PDFInfo
- Publication number
- ES2821877T3 ES2821877T3 ES17740241T ES17740241T ES2821877T3 ES 2821877 T3 ES2821877 T3 ES 2821877T3 ES 17740241 T ES17740241 T ES 17740241T ES 17740241 T ES17740241 T ES 17740241T ES 2821877 T3 ES2821877 T3 ES 2821877T3
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- Prior art keywords
- substituted
- independently selected
- alkyl
- pyrrolidin
- phenyl
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- 239000011435 rock Substances 0.000 title description 38
- 239000003112 inhibitor Substances 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 93
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 72
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 69
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 68
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 64
- 229910021481 rutherfordium Inorganic materials 0.000 claims abstract description 51
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 49
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 42
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 38
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 23
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- 229910052702 rhenium Inorganic materials 0.000 claims abstract description 21
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 21
- 101150105130 RORB gene Proteins 0.000 claims abstract description 20
- 125000003118 aryl group Chemical group 0.000 claims abstract description 17
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 3
- -1 4- (1H-pyrazol-4-yl) phenyl Chemical group 0.000 claims description 87
- 229910052799 carbon Inorganic materials 0.000 claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 22
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 18
- 230000000694 effects Effects 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- NZBBDMMHADSGAF-UHFFFAOYSA-N 1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(C2(CC1)NC1=CC=CC=C1C2)=O NZBBDMMHADSGAF-UHFFFAOYSA-N 0.000 claims description 14
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 12
- GDGXLYITRDZQAV-UHFFFAOYSA-N 5-fluoro-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound N1C2=C(CC31CCN(C3=O)C1=CC=C(C3=CNN=C3)C=C1)C=C(F)C=C2 GDGXLYITRDZQAV-UHFFFAOYSA-N 0.000 claims description 10
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- 108010041788 rho-Associated Kinases Proteins 0.000 claims description 9
- 102000000568 rho-Associated Kinases Human genes 0.000 claims description 9
- RMVQSTDAQPRZSX-UHFFFAOYSA-N 4-fluoro-6-methoxy-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound C1=2NC3(CC1=C(F)C=C(OC)C=2)CCN(C3=O)C1=CC=C(C=2C=NNC=2)C=C1 RMVQSTDAQPRZSX-UHFFFAOYSA-N 0.000 claims description 8
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- GFAUBMISBILPCV-UHFFFAOYSA-N 5-methoxy-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[3H-1-benzofuran-2,3'-pyrrolidine]-2'-one Chemical compound C1=2OC3(CC1=CC(OC)=CC=2)CCN(C3=O)C1=CC=C(C=2C=NNC=2)C=C1 GFAUBMISBILPCV-UHFFFAOYSA-N 0.000 claims description 7
- CZUKRUABVSLHGN-UHFFFAOYSA-N 5-methoxy-1'-[6-methoxy-5-(1H-pyrazol-4-yl)pyridin-2-yl]spiro[1,3-dihydroindene-2,3'-pyrrolidine]-2'-one Chemical compound COC=1C=C2CC3(C(N(CC3)C3=NC(=C(C=C3)C=3C=NNC=3)OC)=O)CC2=CC=1 CZUKRUABVSLHGN-UHFFFAOYSA-N 0.000 claims description 7
- UFIXUBXNBHETDF-UHFFFAOYSA-N 5-fluoro-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindene-2,3'-pyrrolidine]-2'-one Chemical compound C12(CCN(C1=O)C1=CC=C(C=3C=NNC=3)C=C1)CC1=CC=C(F)C=C1C2 UFIXUBXNBHETDF-UHFFFAOYSA-N 0.000 claims description 6
- PXBNCAPNSJKORP-UHFFFAOYSA-N 5-methoxy-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindene-2,3'-pyrrolidine]-2'-one Chemical compound C1=2CC3(CCN(C3=O)C3=CC=C(C=4C=NNC=4)C=C3)CC1=CC=C(OC)C=2 PXBNCAPNSJKORP-UHFFFAOYSA-N 0.000 claims description 5
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- VQFNTTVWRYLUML-UHFFFAOYSA-N 4'-(aminomethyl)-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(C2(C(C1)CN)NC1=CC=CC=C1C2)=O VQFNTTVWRYLUML-UHFFFAOYSA-N 0.000 claims description 4
- KUVFBDVJUBDKEF-UHFFFAOYSA-N 4'-(hydroxymethyl)-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound C(C1CN(C(=O)C21CC1=CC=CC=C1N2)C1=CC=C(C=C1)C=1C=NNC=1)O KUVFBDVJUBDKEF-UHFFFAOYSA-N 0.000 claims description 4
- VDUBYHAYWDQMSL-UHFFFAOYSA-N 4-methyl-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(C2(CC1)NC1=CC=CC(=C1C2)C)=O VDUBYHAYWDQMSL-UHFFFAOYSA-N 0.000 claims description 4
- XESYGOKEGVLFMK-UHFFFAOYSA-N 6-(2-hydroxy-2-methylpropoxy)-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound C(COC1=CC=C2C(NC3(C2)CCN(C3=O)C2=CC=C(C=3C=NNC=3)C=C2)=C1)(C)(O)C XESYGOKEGVLFMK-UHFFFAOYSA-N 0.000 claims description 4
- BVXVOSBBRKWXTM-UHFFFAOYSA-N 6-hydroxy-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound N1C2=C(CC31CCN(C3=O)C1=CC=C(C=C1)C=1C=NNC=1)C=CC(O)=C2 BVXVOSBBRKWXTM-UHFFFAOYSA-N 0.000 claims description 4
- USKLRJZVISLPLA-UHFFFAOYSA-N 6-methoxy-1-methyl-1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[3H-indole-2,3'-pyrrolidine]-2'-one Chemical compound N1(C2=C(CC31CCN(C3=O)C1=CC=C(C=C1)C=1C=NNC=1)C=CC(OC)=C2)C USKLRJZVISLPLA-UHFFFAOYSA-N 0.000 claims description 4
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- 239000003085 diluting agent Substances 0.000 claims description 4
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- MHRHCSNHLAHXPI-UHFFFAOYSA-N 1'-(4-pyridin-4-ylphenyl)spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound C1=2NC3(CC1=CC=CC=2)CCN(C3=O)C1=CC=C(C2=CC=NC=C2)C=C1 MHRHCSNHLAHXPI-UHFFFAOYSA-N 0.000 claims description 3
- KCYPZRNQRHBHRS-UHFFFAOYSA-N 1'-(4-pyridin-4-ylphenyl)spiro[3H-1-benzofuran-2,3'-pyrrolidine]-2'-one Chemical compound O1C2=C(CC31CCN(C3=O)C1=CC=C(C3=CC=NC=C3)C=C1)C=CC=C2 KCYPZRNQRHBHRS-UHFFFAOYSA-N 0.000 claims description 3
- BCKCDMOENWEOTR-UHFFFAOYSA-N 1'-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindene-2,3'-pyrrolidine]-2'-one Chemical compound C1=2CC3(CCN(C3=O)C3=CC=C(C(OC)=C3)C=3C=NNC=3)CC1=CC=CC=2 BCKCDMOENWEOTR-UHFFFAOYSA-N 0.000 claims description 3
- GVRNNYOHGGGEEX-UHFFFAOYSA-N 1'-[4-(1H-indazol-5-yl)phenyl]spiro[1,3-dihydroindole-2,3'-pyrrolidine]-2'-one Chemical compound C1=2NC3(CC1=CC=CC=2)CCN(C3=O)C1=CC=C(C=C1)C1=CC=2C=NNC=2C=C1 GVRNNYOHGGGEEX-UHFFFAOYSA-N 0.000 claims description 3
- YWXBSRRUYFCTFK-UHFFFAOYSA-N 1'-[4-(1H-pyrazol-4-yl)phenyl]spiro[1,3-dihydroindene-2,3'-pyrrolidine]-2'-one Chemical compound N1(CCC2(C1=O)CC1=CC=CC=C1C2)C1=CC=C(C2=CNN=C2)C=C1 YWXBSRRUYFCTFK-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- 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
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- 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
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- 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
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- 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
- C07D403/10—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 linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/20—Spiro-condensed systems
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- Engineering & Computer Science (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
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| US201662359354P | 2016-07-07 | 2016-07-07 | |
| PCT/US2017/040850 WO2018009625A1 (en) | 2016-07-07 | 2017-07-06 | Spirolactams as inhibitors of rock |
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| ES2821877T3 true ES2821877T3 (es) | 2021-04-28 |
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| JP7155102B2 (ja) | 2016-07-07 | 2022-10-18 | ブリストル－マイヤーズ スクイブ カンパニー | Ｒｏｃｋ阻害剤としてのスピロ縮合環尿素 |
| EP3481816B1 (en) | 2016-07-07 | 2020-06-24 | Bristol-Myers Squibb Company | Lactam, cyclic urea and carbamate, and triazolone derivatives as potent and selective rock inhibitors |
| EP3548468B1 (en) | 2016-11-30 | 2020-09-16 | Bristol-Myers Squibb Company | Tricyclic rho kinase inhibitors |
| WO2019014300A1 (en) | 2017-07-12 | 2019-01-17 | Bristol-Myers Squibb Company | PHENYLACETAMIDES AS ROCK INHIBITORS |
| US12060341B2 (en) | 2017-07-12 | 2024-08-13 | Bristol-Myers Squibb Company | Spiroheptanyl hydantoins as ROCK inhibitors |
| TW201908293A (zh) | 2017-07-12 | 2019-03-01 | 美商必治妥美雅史谷比公司 | 作為rock抑制劑之5員及雙環雜環醯胺 |
| CN110914257B (zh) | 2017-07-12 | 2023-05-26 | 百时美施贵宝公司 | 作为rock抑制剂的螺庚基乙内酰脲 |
| JP7234201B2 (ja) | 2017-07-12 | 2023-03-07 | ブリストル－マイヤーズ スクイブ カンパニー | 心不全の治療のためのｒｏｃｋの５員アミノヘテロ環および５，６－または６，６員二環式アミノヘテロ環の阻害剤 |
| ES2937039T3 (es) | 2017-11-03 | 2023-03-23 | Bristol Myers Squibb Co | Inhibidores diazaespiro de ROCK |
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| DK3877364T3 (da) | 2018-11-06 | 2024-09-23 | Cervello Therapeutics LLC | Rock-kinasehæmmere |
| US11248004B2 (en) | 2018-11-06 | 2022-02-15 | Cervello Therapeutics, Llc. | Substituted isoquinolines as rock kinase inhibitors |
| EP3902805A4 (en) | 2018-12-28 | 2023-03-01 | SPV Therapeutics Inc. | CYCLINE-DEPENDENT KINASE INHIBITORS |
| CA3238227A1 (en) | 2021-11-11 | 2023-05-19 | The Doshisha | Cryopreservation preparation for corneal endothelial cells and method for producing said cryopreservation preparation |
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| CN121889155A (zh) | 2023-08-07 | 2026-04-17 | 锐新医药公司 | 用于治疗ras蛋白相关疾病或病症的rmc-6291 |
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| US20250375445A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
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| AU1335897A (en) | 1995-12-21 | 1997-07-17 | Du Pont Merck Pharmaceutical Company, The | Isoxazoline, isothiazoline and pyrazoline factor xa inhibitors |
| ES2228267B1 (es) | 2003-07-30 | 2006-07-01 | Laboratorios Del Dr. Esteve, S.A. | Combinacion de sustancias activas conteniendo al menos un compuesto con afinidad por el receptor del neuropeptido y (npy) y al menos un compuesto con afinidad por el receptor 5-ht6. |
| ES2232292B1 (es) | 2003-07-30 | 2006-11-01 | Laboratorios Del Dr. Esteve, S.A. | Compuestos sulfonamidicos derivados de benzoxazinona, su preparacion y uso como medicamentos. |
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| WO2009133861A1 (ja) | 2008-04-28 | 2009-11-05 | 武田薬品工業株式会社 | 環状アミン化合物 |
| ES2684776T3 (es) | 2013-01-18 | 2018-10-04 | Bristol-Myers Squibb Company | Ftalazinonas e isoquinolinonas como inhibidores de ROCK |
| EP2961746B1 (en) | 2013-02-28 | 2018-01-03 | Bristol-Myers Squibb Company | Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors |
| AR094929A1 (es) * | 2013-02-28 | 2015-09-09 | Bristol Myers Squibb Co | Derivados de fenilpirazol como inhibidores potentes de rock1 y rock2 |
| WO2015002926A1 (en) | 2013-07-02 | 2015-01-08 | Bristol-Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as rock inhibitors |
| JP6434968B2 (ja) | 2013-07-02 | 2018-12-05 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｒｏｃｋ阻害剤としての三環式ピリド−カルボキサミド誘導体 |
| US9902702B2 (en) | 2014-07-15 | 2018-02-27 | Bristol-Myers Squibb Company | Spirocycloheptanes as inhibitors of rock |
| CN107108581B (zh) | 2014-08-21 | 2020-06-23 | 百时美施贵宝公司 | 作为强效rock抑制剂的回接苯甲酰胺衍生物 |
| WO2016065582A1 (en) | 2014-10-30 | 2016-05-06 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| JP6779214B2 (ja) | 2015-01-09 | 2020-11-04 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｒｏｃｋ阻害剤としての環状ウレア |
| ES2730112T3 (es) * | 2015-03-09 | 2019-11-08 | Bristol Myers Squibb Co | Lactamas como inhibidores de ROCK |
| TWI730032B (zh) | 2016-01-13 | 2021-06-11 | 美商必治妥美雅史谷比公司 | 作為ｒｏｃｋ抑制劑之螺庚烷水楊酸醯胺及相關化合物 |
| WO2017205709A1 (en) | 2016-05-27 | 2017-11-30 | Bristol-Myers Squibb Company | Triazolones and tetrazolones as inhibitors of rock |
| JP7155102B2 (ja) | 2016-07-07 | 2022-10-18 | ブリストル－マイヤーズ スクイブ カンパニー | Ｒｏｃｋ阻害剤としてのスピロ縮合環尿素 |
| EP3481816B1 (en) | 2016-07-07 | 2020-06-24 | Bristol-Myers Squibb Company | Lactam, cyclic urea and carbamate, and triazolone derivatives as potent and selective rock inhibitors |
| EP3548468B1 (en) | 2016-11-30 | 2020-09-16 | Bristol-Myers Squibb Company | Tricyclic rho kinase inhibitors |
| CN110914257B (zh) | 2017-07-12 | 2023-05-26 | 百时美施贵宝公司 | 作为rock抑制剂的螺庚基乙内酰脲 |
| TW201908293A (zh) | 2017-07-12 | 2019-03-01 | 美商必治妥美雅史谷比公司 | 作為rock抑制劑之5員及雙環雜環醯胺 |
| JP7234201B2 (ja) | 2017-07-12 | 2023-03-07 | ブリストル－マイヤーズ スクイブ カンパニー | 心不全の治療のためのｒｏｃｋの５員アミノヘテロ環および５，６－または６，６員二環式アミノヘテロ環の阻害剤 |
| WO2019014300A1 (en) | 2017-07-12 | 2019-01-17 | Bristol-Myers Squibb Company | PHENYLACETAMIDES AS ROCK INHIBITORS |
| ES2937039T3 (es) | 2017-11-03 | 2023-03-23 | Bristol Myers Squibb Co | Inhibidores diazaespiro de ROCK |
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| US20190322664A1 (en) | 2019-10-24 |
| US10696674B2 (en) | 2020-06-30 |
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| CN109689639B (zh) | 2022-02-18 |
| CN109689639A (zh) | 2019-04-26 |
| WO2018009625A1 (en) | 2018-01-11 |
| KR20190025682A (ko) | 2019-03-11 |
| JP7113810B2 (ja) | 2022-08-05 |
| KR102491994B1 (ko) | 2023-01-25 |
| EP3481817A1 (en) | 2019-05-15 |
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