BR112017002370B1 - Compostos indóis, composição farmacêutica que os compreende e seu uso na inibição da replicação do vírus da gripe - Google Patents
Compostos indóis, composição farmacêutica que os compreende e seu uso na inibição da replicação do vírus da gripe Download PDFInfo
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- BR112017002370B1 BR112017002370B1 BR112017002370-9A BR112017002370A BR112017002370B1 BR 112017002370 B1 BR112017002370 B1 BR 112017002370B1 BR 112017002370 A BR112017002370 A BR 112017002370A BR 112017002370 B1 BR112017002370 B1 BR 112017002370B1
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- Prior art keywords
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- methyl
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 11
- 241000700605 Viruses Species 0.000 title description 10
- 230000002401 inhibitory effect Effects 0.000 title description 3
- 230000010076 replication Effects 0.000 title description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- 206010022000 influenza Diseases 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 3
- 241000712461 unidentified influenza virus Species 0.000 abstract description 10
- 150000002475 indoles Chemical class 0.000 abstract 1
- 230000009385 viral infection Effects 0.000 abstract 1
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- 239000000203 mixture Substances 0.000 description 172
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 170
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- 238000002360 preparation method Methods 0.000 description 104
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 66
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- 235000019341 magnesium sulphate Nutrition 0.000 description 58
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
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- 238000003818 flash chromatography Methods 0.000 description 15
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
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- WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 7
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Classifications
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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
- C07D401/14—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 containing three or more hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/403—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 carbocyclic rings, e.g. carbazole
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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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
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- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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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
- C07D403/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Molecular Biology (AREA)
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- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14180331 | 2014-08-08 | ||
| EP14180331.2 | 2014-08-08 | ||
| PCT/EP2015/068257 WO2016020526A1 (en) | 2014-08-08 | 2015-08-07 | Indoles for use in influenza virus infection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112017002370A2 BR112017002370A2 (pt) | 2017-12-05 |
| BR112017002370B1 true BR112017002370B1 (pt) | 2022-11-22 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112017002370-9A BR112017002370B1 (pt) | 2014-08-08 | 2015-08-07 | Compostos indóis, composição farmacêutica que os compreende e seu uso na inibição da replicação do vírus da gripe |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US10597390B2 (https=) |
| EP (1) | EP3177609A1 (https=) |
| JP (1) | JP6577570B2 (https=) |
| KR (1) | KR102488479B1 (https=) |
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Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LT3141252T (lt) | 2009-06-17 | 2018-11-12 | Vertex Pharmaceuticals Inc. | Gripo virusų replikacijos inhibitoriai |
| UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| CN106573920B (zh) | 2014-08-08 | 2020-11-10 | 爱尔兰詹森科学公司 | 用于在流感病毒感染中使用的吲哚 |
| EP3294717B1 (en) | 2015-05-13 | 2020-07-29 | Vertex Pharmaceuticals Inc. | Methods of preparing inhibitors of influenza viruses replication |
| EP3294735B8 (en) | 2015-05-13 | 2022-01-05 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| SG11201804225PA (en) | 2015-12-09 | 2018-06-28 | Sunshine Lake Pharma Co Ltd | Inhibitors of influenza virus replication, application methods and uses thereof |
| DK3400225T3 (da) * | 2016-01-07 | 2022-01-03 | Janssen Sciences Ireland Unlimited Co | Pentansyrederivater substitueret med pyrrolo-[2,3-b]pyrimidinpyridiner til behandling af influenzavirusinfektioner |
| WO2017133670A1 (en) * | 2016-02-05 | 2017-08-10 | Savira Pharmaceuticals Gmbh | Pyridine and pyrimidine derivatives and their use in treatment, amelioration or prevention of influenza |
| WO2018033082A1 (en) * | 2016-08-16 | 2018-02-22 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication, application methods and uses thereof |
| WO2018041091A1 (en) * | 2016-08-30 | 2018-03-08 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication, application methods and uses thereof |
| RU2727772C1 (ru) | 2016-09-05 | 2020-07-23 | Гуандун Рэйновент Байотек Ко., Лтд. | Производные пиримидина против вируса гриппа |
| JP7034162B2 (ja) | 2016-12-15 | 2022-03-11 | サンシャイン・レイク・ファーマ・カンパニー・リミテッド | インフルエンザウイルス複製の阻害剤及びその使用 |
| CA3047404A1 (en) * | 2016-12-23 | 2018-06-28 | Aquinnah Pharmaceuticals, Inc. | Compounds, compositions and methods of use |
| CN108276401B (zh) | 2017-01-05 | 2020-12-22 | 广东东阳光药业有限公司 | 流感病毒复制抑制剂及其用途 |
| WO2018157830A1 (en) | 2017-03-02 | 2018-09-07 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication and uses thereof |
| CN108727369B (zh) * | 2017-04-25 | 2023-06-09 | 广东东阳光药业有限公司 | 流感病毒复制抑制剂及其用途 |
| JP7031002B2 (ja) | 2018-03-05 | 2022-03-07 | 広東衆生睿創生物科技有限公司 | ピリジノイミダゾール系化合物の結晶型、塩型及びその製造方法 |
| WO2021012864A1 (zh) * | 2019-07-22 | 2021-01-28 | 广东众生睿创生物科技有限公司 | 嘧啶衍生物的优势盐型及其晶型 |
| CN113045475A (zh) * | 2019-12-27 | 2021-06-29 | 上海泓博智源医药股份有限公司 | 一种5-溴-7-甲基吲哚的制备方法 |
| AU2021313150A1 (en) * | 2020-07-20 | 2023-03-16 | Nido Biosciences, Inc. | Indole compounds as androgen receptor modulators |
| EP4214201A4 (en) * | 2020-09-18 | 2024-10-09 | Sunshine Lake Pharma Co., Ltd. | PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRIMIDINE PIPERAZINE COMPOUNDS |
| CR20250176A (es) * | 2022-10-12 | 2025-06-25 | Maze Therapeutics Inc | Inhibidores del miembro 19 de la familia de portadores de solutos 6a (slc6a19) y métodos de uso de los mismos |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2364340T3 (es) | 2004-03-30 | 2011-08-31 | Vertex Pharmaceuticals Incorporated | Azaindoles útiles como inhibidores de jak y otras proteína quinasas. |
| UA95940C2 (uk) | 2006-01-17 | 2011-09-26 | Вертекс Фармасьютикалс Інкорпорейтед | Азаіндоли як інгібітори кіназ януса |
| LT3141252T (lt) * | 2009-06-17 | 2018-11-12 | Vertex Pharmaceuticals Inc. | Gripo virusų replikacijos inhibitoriai |
| US9326987B2 (en) * | 2010-09-08 | 2016-05-03 | Glaxo Group Limited | Indazole derivatives for use in the treatment of influenza virus infection |
| RU2013132681A (ru) * | 2010-12-16 | 2015-01-27 | Вертекс Фармасьютикалз Инкорпорейтед | Ингибиторы репликации вирусов гриппа |
| CN103562205A (zh) * | 2010-12-16 | 2014-02-05 | 沃泰克斯药物股份有限公司 | 流感病毒复制的抑制剂 |
| UA118010C2 (uk) * | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| JP6096778B2 (ja) | 2011-09-01 | 2017-03-15 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ピロロピラジンキナーゼ阻害剤 |
| EP2858984A1 (en) | 2012-06-08 | 2015-04-15 | Vertex Pharmaceuticals Inc. | Inhibitors of influenza viruses replication |
| LT3068776T (lt) | 2013-11-13 | 2019-08-12 | Vertex Pharmaceuticals Incorporated | Gripo virusų replikacijos inhibitoriai |
| AR101448A1 (es) | 2014-08-08 | 2016-12-21 | Bayer Cropscience Ag | Compuestos sustituidos por halógeno |
| CN106573920B (zh) | 2014-08-08 | 2020-11-10 | 爱尔兰詹森科学公司 | 用于在流感病毒感染中使用的吲哚 |
| AR101401A1 (es) | 2014-08-08 | 2016-12-14 | Bayer Cropscience Ag | Derivados de bipirazol, sustituidos con halógeno |
| CN104592038A (zh) | 2015-01-12 | 2015-05-06 | 烟台万润精细化工股份有限公司 | 一种5,5-二甲基-1,3-环己二胺的制备方法 |
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2015
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- 2015-08-07 WO PCT/EP2015/068257 patent/WO2016020526A1/en not_active Ceased
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2017
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| US10597390B2 (en) | 2020-03-24 |
| ZA201700952B (en) | 2018-12-19 |
| IL250408A0 (en) | 2017-03-30 |
| KR20170039275A (ko) | 2017-04-10 |
| JP2017523225A (ja) | 2017-08-17 |
| MX381488B (es) | 2025-03-12 |
| CA2954751C (en) | 2023-01-17 |
| SG11201700956VA (en) | 2017-03-30 |
| CA2954751A1 (en) | 2016-02-11 |
| AU2015298876B2 (en) | 2020-02-13 |
| EP3177609A1 (en) | 2017-06-14 |
| WO2016020526A1 (en) | 2016-02-11 |
| AU2015298876A1 (en) | 2017-02-02 |
| BR112017002370A2 (pt) | 2017-12-05 |
| MX2017001752A (es) | 2018-02-08 |
| US20170226102A1 (en) | 2017-08-10 |
| KR102488479B1 (ko) | 2023-01-12 |
| EA201790266A1 (ru) | 2017-06-30 |
| CN106573920A (zh) | 2017-04-19 |
| PH12017500207B1 (en) | 2017-07-10 |
| JP6577570B2 (ja) | 2019-09-18 |
| CN106573920B (zh) | 2020-11-10 |
| CL2017000309A1 (es) | 2017-08-18 |
| PH12017500207A1 (en) | 2017-07-10 |
| MA40547A (fr) | 2017-06-14 |
| UA124609C2 (uk) | 2021-10-20 |
| IL250408B (en) | 2020-08-31 |
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