IL301746B2 - Amine-modified heterocyclic compounds as EHMT2 inhibitors, their salts and a method for their synthesis - Google Patents
Amine-modified heterocyclic compounds as EHMT2 inhibitors, their salts and a method for their synthesisInfo
- Publication number
- IL301746B2 IL301746B2 IL301746A IL30174623A IL301746B2 IL 301746 B2 IL301746 B2 IL 301746B2 IL 301746 A IL301746 A IL 301746A IL 30174623 A IL30174623 A IL 30174623A IL 301746 B2 IL301746 B2 IL 301746B2
- Authority
- IL
- Israel
- Prior art keywords
- compound
- crystalline form
- xrpd pattern
- radiation
- peaks selected
- Prior art date
Links
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
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- 150000007530 organic bases Chemical class 0.000 description 1
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- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
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- 230000002035 prolonged effect Effects 0.000 description 1
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- 238000001953 recrystallisation Methods 0.000 description 1
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- 238000003571 reporter gene assay Methods 0.000 description 1
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- 230000002441 reversible effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 230000007727 signaling mechanism Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
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- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000002306 tributylsilyl group Chemical group C(CCC)[Si](CCCC)(CCCC)* 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
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Classifications
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762573917P | 2017-10-18 | 2017-10-18 | |
| PCT/US2018/056428 WO2019079540A1 (en) | 2017-10-18 | 2018-10-18 | AMINO-SUBSTITUTED HETEROCYCLIC COMPOUNDS AS INHIBITORS OF EHMT2, SALTS THEREOF, AND METHODS OF SYNTHESIS THEREOF |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IL301746A IL301746A (en) | 2023-05-01 |
| IL301746B1 IL301746B1 (en) | 2024-09-01 |
| IL301746B2 true IL301746B2 (en) | 2025-01-01 |
Family
ID=66173899
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL301746A IL301746B2 (en) | 2017-10-18 | 2018-10-18 | Amine-modified heterocyclic compounds as EHMT2 inhibitors, their salts and a method for their synthesis |
| IL273974A IL273974B2 (en) | 2017-10-18 | 2020-04-16 | Amine-disubstituted heterocyclic compounds as ehmt2 inhibitors, salts thereof and method for their synthesis |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL273974A IL273974B2 (en) | 2017-10-18 | 2020-04-16 | Amine-disubstituted heterocyclic compounds as ehmt2 inhibitors, salts thereof and method for their synthesis |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US20200247790A1 (https=) |
| EP (1) | EP3697762A4 (https=) |
| JP (2) | JP2021500334A (https=) |
| KR (1) | KR20200101330A (https=) |
| CN (1) | CN111417628A (https=) |
| AU (2) | AU2018353122B2 (https=) |
| BR (1) | BR112020007632A2 (https=) |
| CA (1) | CA3079273A1 (https=) |
| CL (1) | CL2020001009A1 (https=) |
| CO (1) | CO2020005944A2 (https=) |
| EA (1) | EA202090959A1 (https=) |
| IL (2) | IL301746B2 (https=) |
| MA (1) | MA50418A (https=) |
| MX (2) | MX2020007152A (https=) |
| SG (1) | SG11202003225YA (https=) |
| WO (1) | WO2019079540A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11225487B2 (en) | 2017-02-17 | 2022-01-18 | Trevena, Inc. | 7-membered aza-heterocyclic containing δ-opioid receptor modulating compounds, methods of using and making the same |
| CN110621316B (zh) | 2017-04-21 | 2024-01-26 | Epizyme股份有限公司 | 用ehmt2抑制剂进行的组合疗法 |
| KR20240152947A (ko) | 2017-10-18 | 2024-10-22 | 인사이트 코포레이션 | Pi3k-감마 저해제로서의 3차 하이드록시기로 치환된 축합된 이미다졸 유도체 |
| CR20250050A (es) | 2018-09-05 | 2025-03-19 | Incyte Corp | Formas cristalinas de un inhibidor de fosfoinositida 3–quinasa (pi3k) (divisional 2021-0165) |
| CN114249785B (zh) * | 2020-09-23 | 2024-04-05 | 常州方圆制药有限公司 | 一种2-腺苷n-吡唑的衍生物瑞加德松的制备方法 |
| JP2023546729A (ja) * | 2020-10-27 | 2023-11-07 | トレベナ・インコーポレイテッド | デルタオピオイドモジュレーターの結晶形及び非晶形 |
| WO2025240956A1 (en) * | 2024-05-17 | 2025-11-20 | Yale University | G9a/ehmt2 inhibitor use for prader-willi syndrome |
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| MXPA06003054A (es) * | 2003-09-18 | 2006-05-31 | Novartis Ag | 2,4-di-(fenil-amino)-pirimidinas utiles en el tratamiento de trastornos proliferativos. |
| US8604042B2 (en) * | 2005-11-01 | 2013-12-10 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
| CN103626742B (zh) * | 2005-11-01 | 2017-04-26 | 塔格根公司 | 激酶的联-芳基间-嘧啶抑制剂 |
| US9284272B2 (en) * | 2014-03-28 | 2016-03-15 | Abbvie Inc. | Inhibitors of histone methyltransferase G9a |
| DK3154957T3 (da) * | 2014-06-16 | 2020-02-17 | Fundacion Para La Investig Medica Aplicada | Hidtil ukendte forbindelser som dobbelte inhibitorer af histonmethyltransferaser og dna-methyltransferaser |
| EP3157524A4 (en) * | 2014-06-23 | 2017-12-06 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
| HUE064145T2 (hu) * | 2016-04-15 | 2024-03-28 | Epizyme Inc | Amin-szubsztituált aril- vagy heteroaril vegyületek, mint EHMT1 és EHMT2 inhibitorok |
| ES2955132T3 (es) * | 2016-12-19 | 2023-11-28 | Epizyme Inc | Compuestos heterocíclicos sustituidos con amina como inhibidores de EHMT2 y métodos de uso de los mismos |
| EP3600318A4 (en) * | 2017-03-31 | 2021-06-09 | Epizyme, Inc. | METHOD OF USING EHMT2 INHIBITORS |
| EP3697420A4 (en) * | 2017-10-18 | 2021-11-24 | Epizyme, Inc. | METHOD OF USING EHMT2 INHIBITORS IN IMMUNOTHERAPY |
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2018
- 2018-10-18 CA CA3079273A patent/CA3079273A1/en active Pending
- 2018-10-18 BR BR112020007632-5A patent/BR112020007632A2/pt unknown
- 2018-10-18 MA MA050418A patent/MA50418A/fr unknown
- 2018-10-18 WO PCT/US2018/056428 patent/WO2019079540A1/en not_active Ceased
- 2018-10-18 EP EP18869308.9A patent/EP3697762A4/en not_active Withdrawn
- 2018-10-18 AU AU2018353122A patent/AU2018353122B2/en active Active
- 2018-10-18 KR KR1020207013781A patent/KR20200101330A/ko not_active Ceased
- 2018-10-18 EA EA202090959A patent/EA202090959A1/ru unknown
- 2018-10-18 CN CN201880077022.4A patent/CN111417628A/zh active Pending
- 2018-10-18 US US16/756,565 patent/US20200247790A1/en not_active Abandoned
- 2018-10-18 SG SG11202003225YA patent/SG11202003225YA/en unknown
- 2018-10-18 JP JP2020521599A patent/JP2021500334A/ja not_active Withdrawn
- 2018-10-18 IL IL301746A patent/IL301746B2/en unknown
- 2018-10-18 MX MX2020007152A patent/MX2020007152A/es unknown
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2020
- 2020-04-15 CL CL2020001009A patent/CL2020001009A1/es unknown
- 2020-04-16 IL IL273974A patent/IL273974B2/en unknown
- 2020-05-15 CO CONC2020/0005944A patent/CO2020005944A2/es unknown
- 2020-07-13 MX MX2024012124A patent/MX2024012124A/es unknown
-
2022
- 2022-03-24 US US17/703,155 patent/US20220324851A1/en not_active Abandoned
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2023
- 2023-01-11 JP JP2023002371A patent/JP2023036991A/ja active Pending
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2024
- 2024-02-22 AU AU2024201165A patent/AU2024201165A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL301746A (en) | 2023-05-01 |
| CN111417628A (zh) | 2020-07-14 |
| CO2020005944A2 (es) | 2020-07-31 |
| BR112020007632A2 (pt) | 2020-09-29 |
| SG11202003225YA (en) | 2020-05-28 |
| EP3697762A4 (en) | 2021-04-07 |
| JP2023036991A (ja) | 2023-03-14 |
| CL2020001009A1 (es) | 2020-12-18 |
| MX2024012124A (es) | 2025-02-10 |
| IL301746B1 (en) | 2024-09-01 |
| MA50418A (fr) | 2021-04-07 |
| US20220324851A1 (en) | 2022-10-13 |
| AU2024201165A1 (en) | 2024-03-14 |
| EP3697762A1 (en) | 2020-08-26 |
| IL273974B1 (en) | 2023-04-01 |
| MX2020007152A (es) | 2020-12-10 |
| CA3079273A1 (en) | 2019-04-25 |
| AU2018353122B2 (en) | 2023-11-23 |
| IL273974B2 (en) | 2023-08-01 |
| IL273974A (en) | 2020-05-31 |
| WO2019079540A1 (en) | 2019-04-25 |
| KR20200101330A (ko) | 2020-08-27 |
| AU2018353122A1 (en) | 2020-06-04 |
| US20200247790A1 (en) | 2020-08-06 |
| JP2021500334A (ja) | 2021-01-07 |
| EA202090959A1 (ru) | 2020-07-13 |
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