ES2898835T3 - Azol amidas y aminas como inhibidores de la integrina alfav - Google Patents
Azol amidas y aminas como inhibidores de la integrina alfav Download PDFInfo
- Publication number
- ES2898835T3 ES2898835T3 ES17801235T ES17801235T ES2898835T3 ES 2898835 T3 ES2898835 T3 ES 2898835T3 ES 17801235 T ES17801235 T ES 17801235T ES 17801235 T ES17801235 T ES 17801235T ES 2898835 T3 ES2898835 T3 ES 2898835T3
- Authority
- ES
- Spain
- Prior art keywords
- carboxamido
- propanoic
- ethyl
- parazol
- tetrah
- 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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- -1 Azole amides Chemical class 0.000 title claims abstract description 136
- 239000003112 inhibitor Substances 0.000 title description 22
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 16
- 150000001412 amines Chemical class 0.000 title description 8
- 108010040765 Integrin alphaV Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 138
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 60
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 56
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 125000003118 aryl group Chemical group 0.000 claims abstract description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 40
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 35
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 32
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 31
- 229910003827 NRaRb Inorganic materials 0.000 claims abstract description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 26
- 239000001257 hydrogen Substances 0.000 claims abstract description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 24
- 125000004429 atom Chemical group 0.000 claims abstract description 22
- 125000005843 halogen group Chemical group 0.000 claims abstract description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 17
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 12
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 5
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims abstract description 3
- 229910052705 radium Inorganic materials 0.000 claims abstract description 3
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims description 91
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 32
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- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 18
- 235000019260 propionic acid Nutrition 0.000 claims description 18
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- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 208000027866 inflammatory disease Diseases 0.000 claims description 7
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
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- 206010042953 Systemic sclerosis Diseases 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
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- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 4
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- 230000002440 hepatic effect Effects 0.000 claims description 4
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 208000020832 chronic kidney disease Diseases 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
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- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 210000004696 endometrium Anatomy 0.000 claims description 2
- 210000003238 esophagus Anatomy 0.000 claims description 2
- 210000000232 gallbladder Anatomy 0.000 claims description 2
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- 210000002429 large intestine Anatomy 0.000 claims description 2
- 210000000867 larynx Anatomy 0.000 claims description 2
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- 210000002307 prostate Anatomy 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 210000000952 spleen Anatomy 0.000 claims description 2
- 210000001550 testis Anatomy 0.000 claims description 2
- 210000001685 thyroid gland Anatomy 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- DIIXDEPENTUOCY-QHCPKHFHSA-N (3S)-3-(3-bromo-5-tert-butylphenyl)-3-[[5-(hydroxymethyl)-1-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrazole-4-carbonyl]amino]propanoic acid Chemical compound BrC=1C=C(C=C(C=1)C(C)(C)C)[C@H](CC(=O)O)NC(=O)C=1C=NN(C=1CO)CCC1=NC=2NCCCC=2C=C1 DIIXDEPENTUOCY-QHCPKHFHSA-N 0.000 claims 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims 2
- SPVDEHMYFLSPNJ-NRFANRHFSA-N (2S)-2-(phenylmethoxycarbonylamino)-3-[[1-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrazole-4-carbonyl]amino]propanoic acid Chemical compound C1=CC=CC=C1COC(=O)N[C@@H](CNC(=O)C1=CN(CCC2=CC=C3CCCNC3=N2)N=C1)C(=O)O SPVDEHMYFLSPNJ-NRFANRHFSA-N 0.000 claims 1
- KVUCFABOFHNCFE-NRFANRHFSA-N (2S)-2-[(4-methoxyphenyl)sulfonylamino]-3-[[1-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrazole-4-carbonyl]amino]propanoic acid Chemical compound COC1=CC=C(C=C1)S(=O)(=O)N[C@H](C(=O)O)CNC(=O)C=1C=NN(C=1)CCC1=NC=2NCCCC=2C=C1 KVUCFABOFHNCFE-NRFANRHFSA-N 0.000 claims 1
- VJCXCNXQZBUOBV-FQEVSTJZSA-N (3S)-3-(3-fluoro-4-methoxyphenyl)-3-[[3-(hydroxymethyl)-1-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrazole-4-carbonyl]amino]propanoic acid Chemical compound FC=1C=C(C=CC=1OC)[C@H](CC(=O)O)NC(=O)C=1C(=NN(C=1)CCC1=NC=2NCCCC=2C=C1)CO VJCXCNXQZBUOBV-FQEVSTJZSA-N 0.000 claims 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 1
- YNTJKQDWYXUTLZ-UHFFFAOYSA-N 2-(3-chlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=CC(Cl)=C1 YNTJKQDWYXUTLZ-UHFFFAOYSA-N 0.000 claims 1
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 claims 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 claims 1
- 206010052779 Transplant rejections Diseases 0.000 claims 1
- NXXGJRZWYCYPCB-HBWRTXEVSA-N dihydroresveratrol-3-O-beta-D-glucuronide Chemical group O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC1=CC(O)=CC(CCC=2C=CC(O)=CC=2)=C1 NXXGJRZWYCYPCB-HBWRTXEVSA-N 0.000 claims 1
- 230000002500 effect on skin Effects 0.000 claims 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 227
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 226
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 95
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- 239000003039 volatile agent Substances 0.000 description 53
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- 235000019257 ammonium acetate Nutrition 0.000 description 52
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Classifications
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Landscapes
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- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
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Applications Claiming Priority (2)
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| US201662418838P | 2016-11-08 | 2016-11-08 | |
| PCT/US2017/060390 WO2018089358A1 (en) | 2016-11-08 | 2017-11-07 | Azole amides and amines as alpha v integrin inhibitors |
Publications (1)
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| ES2898835T3 true ES2898835T3 (es) | 2022-03-09 |
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| ES17801235T Active ES2898835T3 (es) | 2016-11-08 | 2017-11-07 | Azol amidas y aminas como inhibidores de la integrina alfav |
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| EP (1) | EP3538527B1 (enExample) |
| JP (1) | JP7128811B2 (enExample) |
| KR (1) | KR102510858B1 (enExample) |
| CN (1) | CN110167933B (enExample) |
| AU (1) | AU2017359028A1 (enExample) |
| BR (1) | BR112019009245A2 (enExample) |
| CA (1) | CA3042684A1 (enExample) |
| EA (1) | EA201991121A1 (enExample) |
| ES (1) | ES2898835T3 (enExample) |
| IL (1) | IL266465A (enExample) |
| MA (1) | MA46746A (enExample) |
| MX (1) | MX2019005234A (enExample) |
| WO (1) | WO2018089358A1 (enExample) |
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| CN109996541A (zh) | 2016-09-07 | 2019-07-09 | 普利安特治疗公司 | N-酰基氨基酸化合物及其使用方法 |
| CA3045491A1 (en) | 2016-12-29 | 2018-07-19 | Indalo Therapeutics, Inc. | Integrin antagonists |
| EP4159727B1 (en) | 2017-02-28 | 2026-04-08 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| US11046685B2 (en) | 2017-02-28 | 2021-06-29 | Morphic Therapeutic, Inc. | Inhibitors of (α-v)(β-6) integrin |
| AU2019327475B2 (en) | 2018-08-29 | 2025-06-05 | Morphic Therapeutic, Inc. | INHIBITING αV β6 INTEGRIN |
| PT3844162T (pt) | 2018-08-29 | 2025-03-28 | Morphic Therapeutic Inc | Inibidores da integrina alfa v beta6 |
| WO2020047208A1 (en) | 2018-08-29 | 2020-03-05 | Morphic Therapeutic, Inc. | Inhibitors of (alpha-v)(beta-6) integrin |
| ES2987796T3 (es) | 2018-10-30 | 2024-11-18 | Gilead Sciences Inc | Derivados de N-benzoil-fenilalanina como inhibidores de la integrina alfa4beta7 para el tratamiento de enfermedades inflamatorias |
| DK3873884T3 (da) | 2018-10-30 | 2025-02-17 | Gilead Sciences Inc | 3-(quinolin-8-yl)-1,4-dihydropyrido[3,4-d]pyrimidin-2,4-dion-derivater som alpha4beta7-integrinhæmmere til behandling af inflammatoriske sygdomme |
| WO2020092394A1 (en) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | Imidazopyridine derivatives as alpha4beta7 integrin inhibitors |
| WO2020092401A1 (en) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | COMPOUNDS FOR INHIBITION OF ALPHA 4β7 INTEGRIN |
| AU2020329207B2 (en) | 2019-08-14 | 2024-02-29 | Gilead Sciences, Inc. | Compounds for inhibition of alpha 4 beta 7 integrin |
| GB202010626D0 (en) | 2020-07-10 | 2020-08-26 | Univ Nottingham | Compound |
| US20240174603A1 (en) * | 2021-02-08 | 2024-05-30 | Rappta Therapeutics Oy | Modulators of protein phosphatase 2a (pp2a) and methods using same |
| IL305752A (en) * | 2021-03-10 | 2023-11-01 | Dice Molecules Sv Inc | INTEGRIN INHIBITORS OF ALPHA V BETA 6 AND ALPHA V BETA 1 AND THEIR USES |
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| US5849736A (en) * | 1993-11-24 | 1998-12-15 | The Dupont Merck Pharmaceutical Company | Isoxazoline and isoxazole fibrinogen receptor antagonists |
| ZA972195B (en) | 1996-03-15 | 1998-09-14 | Du Pont Merck Pharma | Spirocycle integrin inhibitors |
| JP2001524481A (ja) * | 1997-11-26 | 2001-12-04 | デュポン ファーマシューティカルズ カンパニー | αＶβ３アンタゴニストとしての１，３，４−チアジアゾール類および１，３，４−オキサジアゾール類 |
| EP1047425A4 (en) | 1997-12-17 | 2009-04-22 | Merck & Co Inc | INTEGRIN RECEPTOR ANTAGONISTS |
| AU748621B2 (en) | 1998-08-13 | 2002-06-06 | Merck & Co., Inc. | Integrin receptor antagonists |
| DE60035779T2 (de) * | 1999-06-02 | 2008-04-30 | Merck & Co., Inc. | Alpha v integrin-rezeptor antagonisten |
| JP2004511434A (ja) | 2000-06-15 | 2004-04-15 | ファルマシア・コーポレーション | インテグリン受容体アンタゴニストとしてのヘテロアリールアルカン酸 |
| WO2002060438A1 (en) | 2001-01-29 | 2002-08-08 | 3-Dimensional Pharmaceuticals, Inc. | Substituted indoles and their use as integrin antagonists |
| EP1539739B1 (en) | 2002-08-16 | 2010-11-24 | Janssen Pharmaceutica NV | Piperidinyl compounds that selectively bind integrins |
| ES2308227T3 (es) | 2003-10-01 | 2008-12-01 | Merck Patent Gmbh | Antagonistas de integrina alfavbeta3 y alfavbeta6 como agentes antifibroticos. |
| WO2006108040A1 (en) | 2005-04-05 | 2006-10-12 | Janssen Pharmaceutica, N.V. | Substituted indoles and their use as integrin antagonists |
| JP2009539815A (ja) | 2006-06-09 | 2009-11-19 | アストラゼネカ アクチボラグ | 固形腫瘍の治療用のａ５ｂ１アンタゴニストとしてのＮ−（ベンゾイル）−Ｏ−［２−（ピリジン−２−イルアミノ）エチル］−Ｌ−チロシン誘導体と関連化合物 |
| WO2008125811A1 (en) | 2007-04-11 | 2008-10-23 | Astrazeneca Ab | N-[HETEROARYLCARBONYL]-S-THIENYL-L-ALANINE DERIVATIVES AS α5β1 ANTAGONISTS |
| ITFI20100019A1 (it) * | 2010-02-12 | 2011-08-13 | Univ Firenze | Inibitori peptidomimetici di integrine basati sull'1,2,3-triazolo per la diagnosi e terapia dei tumori. |
| BR112015004427A2 (pt) | 2012-10-26 | 2017-07-04 | Hoffmann La Roche | compostos , métodos para o tratamento de um estado inflamatório , da artrite reumatóide , da asma , de um distúrbio imunológico e de um distúrbio imune e composição farmacêutica |
| EP3266782B1 (en) * | 2013-02-07 | 2019-10-30 | SciFluor Life Sciences, Inc. | Fluorinated integrin antagonists |
| GB201305668D0 (en) | 2013-03-28 | 2013-05-15 | Glaxosmithkline Ip Dev Ltd | Avs6 Integrin Antagonists |
| TWI667233B (zh) | 2013-12-19 | 2019-08-01 | 德商拜耳製藥公司 | 新穎吲唑羧醯胺，其製備方法、含彼等之醫藥製劑及其製造醫藥之用途 |
| GB201417002D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201417018D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417011D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417094D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| EP3925959A1 (en) | 2015-02-19 | 2021-12-22 | OcuTerra Therapeutics, Inc. | Fluorinated derivatives of 3-(2-oxo-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)imidazolidin-1-yl)propanoic acid and uses thereof |
| AU2016228852A1 (en) | 2015-03-10 | 2017-10-19 | The Regents Of The University Of California | Anti-alphavbeta1 integrin inhibitors and methods of use |
| PT3538525T (pt) * | 2016-11-08 | 2022-08-16 | Bristol Myers Squibb Co | Ácidos propiónicos 3-substituídos por inibidores de alfa v integrina |
-
2017
- 2017-11-07 AU AU2017359028A patent/AU2017359028A1/en not_active Abandoned
- 2017-11-07 CA CA3042684A patent/CA3042684A1/en not_active Abandoned
- 2017-11-07 MX MX2019005234A patent/MX2019005234A/es unknown
- 2017-11-07 EP EP17801235.7A patent/EP3538527B1/en active Active
- 2017-11-07 BR BR112019009245A patent/BR112019009245A2/pt not_active Application Discontinuation
- 2017-11-07 MA MA046746A patent/MA46746A/fr unknown
- 2017-11-07 CN CN201780082144.8A patent/CN110167933B/zh active Active
- 2017-11-07 ES ES17801235T patent/ES2898835T3/es active Active
- 2017-11-07 US US16/347,829 patent/US10851098B2/en active Active
- 2017-11-07 WO PCT/US2017/060390 patent/WO2018089358A1/en not_active Ceased
- 2017-11-07 KR KR1020197016076A patent/KR102510858B1/ko active Active
- 2017-11-07 JP JP2019523847A patent/JP7128811B2/ja active Active
- 2017-11-07 EA EA201991121A patent/EA201991121A1/ru unknown
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2019
- 2019-05-06 IL IL266465A patent/IL266465A/en unknown
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| US20190256513A1 (en) | 2019-08-22 |
| EP3538527B1 (en) | 2021-10-13 |
| KR20190076030A (ko) | 2019-07-01 |
| IL266465A (en) | 2019-07-31 |
| EP3538527A1 (en) | 2019-09-18 |
| WO2018089358A1 (en) | 2018-05-17 |
| CA3042684A1 (en) | 2018-05-17 |
| US10851098B2 (en) | 2020-12-01 |
| MX2019005234A (es) | 2019-08-12 |
| KR102510858B1 (ko) | 2023-03-15 |
| CN110167933B (zh) | 2022-06-21 |
| EA201991121A1 (ru) | 2019-11-29 |
| AU2017359028A1 (en) | 2019-06-20 |
| BR112019009245A2 (pt) | 2019-07-16 |
| CN110167933A (zh) | 2019-08-23 |
| JP2019537603A (ja) | 2019-12-26 |
| MA46746A (fr) | 2019-09-18 |
| JP7128811B2 (ja) | 2022-08-31 |
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