CN112250692B - 可用于合成软海绵素大环内酯的大环化反应以及中间体和其他片段 - Google Patents
可用于合成软海绵素大环内酯的大环化反应以及中间体和其他片段 Download PDFInfo
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- CN112250692B CN112250692B CN202011142074.0A CN202011142074A CN112250692B CN 112250692 B CN112250692 B CN 112250692B CN 202011142074 A CN202011142074 A CN 202011142074A CN 112250692 B CN112250692 B CN 112250692B
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- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000005834 sharpless asymmetric dihydroxylation reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
- FGGPAWQCCGEWTJ-UHFFFAOYSA-M sodium;2,3-bis(sulfanyl)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(S)CS FGGPAWQCCGEWTJ-UHFFFAOYSA-M 0.000 description 1
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000006169 tetracyclic group Chemical group 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical compound C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 1
- 229930004006 tropane Natural products 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Priority Applications (1)
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| CN202011142074.0A CN112250692B (zh) | 2015-05-07 | 2016-05-09 | 可用于合成软海绵素大环内酯的大环化反应以及中间体和其他片段 |
Applications Claiming Priority (7)
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| US201562158506P | 2015-05-07 | 2015-05-07 | |
| US62/158506 | 2015-05-07 | ||
| US201662291918P | 2016-02-05 | 2016-02-05 | |
| US62/291918 | 2016-02-05 | ||
| CN201680040015.8A CN107849057B (zh) | 2015-05-07 | 2016-05-09 | 用于合成软海绵素大环内酯的大环化反应及中间体和其他片段 |
| CN202011142074.0A CN112250692B (zh) | 2015-05-07 | 2016-05-09 | 可用于合成软海绵素大环内酯的大环化反应以及中间体和其他片段 |
| PCT/US2016/031546 WO2016179607A1 (en) | 2015-05-07 | 2016-05-09 | Macrocyclization reactions and intermediates and other fragments useful in the synthesis of halichondrin macrolides |
Related Parent Applications (1)
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| CN201680040015.8A Division CN107849057B (zh) | 2015-05-07 | 2016-05-09 | 用于合成软海绵素大环内酯的大环化反应及中间体和其他片段 |
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| CN112250692A CN112250692A (zh) | 2021-01-22 |
| CN112250692B true CN112250692B (zh) | 2023-08-29 |
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| CN202011142074.0A Active CN112250692B (zh) | 2015-05-07 | 2016-05-09 | 可用于合成软海绵素大环内酯的大环化反应以及中间体和其他片段 |
| CN202310983219.7A Pending CN117024469A (zh) | 2015-05-07 | 2016-05-09 | 可用于合成软海绵素大环内酯的大环化反应以及中间体和其他片段 |
| CN201680040015.8A Active CN107849057B (zh) | 2015-05-07 | 2016-05-09 | 用于合成软海绵素大环内酯的大环化反应及中间体和其他片段 |
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| CN201680040015.8A Active CN107849057B (zh) | 2015-05-07 | 2016-05-09 | 用于合成软海绵素大环内酯的大环化反应及中间体和其他片段 |
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| JP (1) | JP6840090B2 (https=) |
| KR (2) | KR102743950B1 (https=) |
| CN (3) | CN112250692B (https=) |
| IL (2) | IL255408B (https=) |
| MX (2) | MX392296B (https=) |
| RU (2) | RU2020141025A (https=) |
| WO (1) | WO2016179607A1 (https=) |
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| SI2522663T1 (sl) | 2004-06-03 | 2015-08-31 | Eisai R&D Management Co., Ltd. | Vmesne spojine za pripravo halihondrina B |
| BRPI0817909B1 (pt) | 2007-10-03 | 2022-06-21 | Eisai R&D Management Co., Ltd | Métodos de obtenção e de preparação de uma composição diastereomericamente pura, compostos, e método para produzir os referidos compostos |
| RU2579511C2 (ru) | 2010-01-26 | 2016-04-10 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Производные фуро[3,2-в]пирана, применимые в синтезе аналогов |
| BR112016009452B1 (pt) * | 2013-11-04 | 2022-06-07 | Eisai R&D Management Co., Ltd | Métodos de preparar intermediários na síntese de eribulina, métodos de preparar eribulina e mesilato de eribulina, e compostos intermediários |
| EP3077399B1 (en) | 2013-12-06 | 2019-02-20 | Eisai R&D Management Co., Ltd. | Methods useful in the synthesis of halichondrin b analogs |
| US10556910B2 (en) | 2014-06-30 | 2020-02-11 | President And Fellows Of Harvard College | Synthesis of halichondrin analogs and uses thereof |
| US10344038B2 (en) | 2015-04-30 | 2019-07-09 | President And Fellows Of Harvard College | Chromium-mediated coupling and application to the synthesis of halichondrins |
| MX392296B (es) | 2015-05-07 | 2025-03-24 | Eisai R&D Man Co Ltd | Reacciones de macrociclizacion e intermediarios y otros fragmentos utiles en la sintesis de macrolidos de halicondrina. |
| CN108601760A (zh) | 2016-02-12 | 2018-09-28 | 卫材R&D管理有限公司 | 艾日布林的合成中的中间体及相关的合成方法 |
| KR102404629B1 (ko) | 2016-06-30 | 2022-06-02 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 할리콘드린 마크롤리드 및 그의 유사체의 합성에 유용한 프린스 반응 및 중간체 |
| JP6978758B2 (ja) | 2016-11-11 | 2021-12-08 | プレジデント アンド フェローズ オブ ハーバード カレッジ | パラジウム媒介ケトール化 |
| US9938288B1 (en) | 2017-04-05 | 2018-04-10 | President And Fellows Of Harvard College | Macrocyclic compound and uses thereof |
| SMT202200455T1 (it) | 2017-04-05 | 2023-01-13 | Harvard College | Composto macrociclico e relativi usi |
| WO2019010363A1 (en) * | 2017-07-06 | 2019-01-10 | President And Fellows Of Harvard College | HALICHONDRINES SYNTHESIS |
| US11498892B2 (en) | 2017-07-06 | 2022-11-15 | President And Fellows Of Harvard College | Fe/Cu-mediated ketone synthesis |
| WO2019099646A1 (en) | 2017-11-15 | 2019-05-23 | President And Fellows Of Harvard College | Macrocyclic compounds and uses thereof |
| IL275729B2 (en) * | 2018-01-03 | 2023-09-01 | Eisai R&D Man Co Ltd | Prins reaction and compounds useful in the synthesis of helicondrin macrolides and their analogs |
| CN115583875B (zh) * | 2022-09-28 | 2023-12-01 | 联化科技（台州）有限公司 | 在连续流反应器中将烯丙型醇氧化为α,β-不饱和醛酮的方法 |
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| SU652180A1 (ru) | 1975-12-16 | 1979-03-15 | Краснодарский политехнический институт | 1(Фурил-2,)-2-(2-,, формилфурил-5,, ) этилен или его метильное производное как промежуточный продукт дл синтеза фуран-2,5-дикарбоновой кислоты и способ его получени |
| US5436238A (en) | 1992-03-12 | 1995-07-25 | President And Fellows Of Harvard College | Halichondrins and related compounds |
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| TW255880B (https=) | 1992-09-09 | 1995-09-01 | Hoechst Ag | |
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| MX392296B (es) | 2015-05-07 | 2025-03-24 | Eisai R&D Man Co Ltd | Reacciones de macrociclizacion e intermediarios y otros fragmentos utiles en la sintesis de macrolidos de halicondrina. |
| CN108601760A (zh) | 2016-02-12 | 2018-09-28 | 卫材R&D管理有限公司 | 艾日布林的合成中的中间体及相关的合成方法 |
| KR102404629B1 (ko) | 2016-06-30 | 2022-06-02 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 할리콘드린 마크롤리드 및 그의 유사체의 합성에 유용한 프린스 반응 및 중간체 |
| WO2018217894A1 (en) | 2017-05-24 | 2018-11-29 | Eisai R&D Management Co., Ltd. | Fluorine-labelled halichondrin derivatives and related methods of synthesis |
| IL275729B2 (en) | 2018-01-03 | 2023-09-01 | Eisai R&D Man Co Ltd | Prins reaction and compounds useful in the synthesis of helicondrin macrolides and their analogs |
-
2016
- 2016-05-09 MX MX2021002629A patent/MX392296B/es unknown
- 2016-05-09 KR KR1020177034639A patent/KR102743950B1/ko active Active
- 2016-05-09 RU RU2020141025A patent/RU2020141025A/ru unknown
- 2016-05-09 WO PCT/US2016/031546 patent/WO2016179607A1/en not_active Ceased
- 2016-05-09 US US15/571,921 patent/US10308661B2/en active Active
- 2016-05-09 MX MX2017014237A patent/MX380284B/es unknown
- 2016-05-09 RU RU2017142100A patent/RU2739034C2/ru active
- 2016-05-09 CN CN202011142074.0A patent/CN112250692B/zh active Active
- 2016-05-09 JP JP2017558008A patent/JP6840090B2/ja active Active
- 2016-05-09 CN CN202310983219.7A patent/CN117024469A/zh active Pending
- 2016-05-09 EP EP16790247.7A patent/EP3292130B1/en not_active Not-in-force
- 2016-05-09 CN CN201680040015.8A patent/CN107849057B/zh active Active
- 2016-05-09 KR KR1020247041347A patent/KR20250012090A/ko active Pending
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2017
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2019
- 2019-04-18 US US16/387,820 patent/US10913749B2/en active Active
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2020
- 2020-07-29 IL IL276376A patent/IL276376B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6214865B1 (en) * | 1998-06-17 | 2001-04-10 | Eisai Co., Ltd. | Macrocyclic analogs and methods of their use and preparation |
| WO2013142999A1 (en) * | 2012-03-30 | 2013-10-03 | Alphora Research Inc. | Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein |
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| IL255408B (en) | 2020-08-31 |
| MX2017014237A (es) | 2018-09-17 |
| IL276376B (en) | 2021-09-30 |
| MX392296B (es) | 2025-03-24 |
| RU2739034C2 (ru) | 2020-12-21 |
| US10913749B2 (en) | 2021-02-09 |
| CN112250692A (zh) | 2021-01-22 |
| IL276376A (en) | 2020-09-30 |
| MX380284B (es) | 2025-03-12 |
| RU2017142100A (ru) | 2019-06-07 |
| MX2021002629A (es) | 2022-05-13 |
| CN107849057A (zh) | 2018-03-27 |
| US20180118755A1 (en) | 2018-05-03 |
| EP3292130B1 (en) | 2020-09-30 |
| WO2016179607A1 (en) | 2016-11-10 |
| US10308661B2 (en) | 2019-06-04 |
| EP3292130A1 (en) | 2018-03-14 |
| CN117024469A (zh) | 2023-11-10 |
| JP2018516885A (ja) | 2018-06-28 |
| KR20180013943A (ko) | 2018-02-07 |
| RU2017142100A3 (https=) | 2019-12-26 |
| RU2020141025A (ru) | 2020-12-28 |
| IL255408A0 (en) | 2017-12-31 |
| KR20250012090A (ko) | 2025-01-23 |
| JP6840090B2 (ja) | 2021-03-10 |
| KR102743950B1 (ko) | 2024-12-18 |
| US20190308992A1 (en) | 2019-10-10 |
| CN107849057B (zh) | 2020-11-10 |
| EP3292130A4 (en) | 2018-12-05 |
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