AR109437A1 - Derivados de n-(piridin-2-il)piridina-sulfonamida y su uso en el tratamiento de enfermedades - Google Patents
Derivados de n-(piridin-2-il)piridina-sulfonamida y su uso en el tratamiento de enfermedadesInfo
- Publication number
- AR109437A1 AR109437A1 ARP170102384A ARP170102384A AR109437A1 AR 109437 A1 AR109437 A1 AR 109437A1 AR P170102384 A ARP170102384 A AR P170102384A AR P170102384 A ARP170102384 A AR P170102384A AR 109437 A1 AR109437 A1 AR 109437A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- substituted
- alkoxy
- nhr11
- hydroxy
- Prior art date
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract 4
- 201000010099 disease Diseases 0.000 title abstract 2
- 229940124530 sulfonamide Drugs 0.000 title 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 18
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 9
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 abstract 9
- 125000000623 heterocyclic group Chemical group 0.000 abstract 9
- 229910052739 hydrogen Inorganic materials 0.000 abstract 9
- 239000001257 hydrogen Substances 0.000 abstract 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 8
- 125000000217 alkyl group Chemical group 0.000 abstract 8
- 125000001475 halogen functional group Chemical group 0.000 abstract 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 8
- 229910052736 halogen Inorganic materials 0.000 abstract 6
- 150000002367 halogens Chemical group 0.000 abstract 6
- 150000002825 nitriles Chemical group 0.000 abstract 5
- 125000001424 substituent group Chemical group 0.000 abstract 4
- 150000001875 compounds Chemical class 0.000 abstract 3
- 125000004043 oxo group Chemical group O=* 0.000 abstract 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 3
- 229920006395 saturated elastomer Polymers 0.000 abstract 3
- 208000035475 disorder Diseases 0.000 abstract 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 abstract 1
- 201000003883 Cystic fibrosis Diseases 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000004438 haloalkoxy group Chemical group 0.000 abstract 1
- 125000001188 haloalkyl group Chemical group 0.000 abstract 1
- 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- WCYWZMWISLQXQU-FIBGUPNXSA-N trideuteriomethane Chemical group [2H][C]([2H])[2H] WCYWZMWISLQXQU-FIBGUPNXSA-N 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- 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
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662380659P | 2016-08-29 | 2016-08-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR109437A1 true AR109437A1 (es) | 2018-11-28 |
Family
ID=59923496
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP170102384A AR109437A1 (es) | 2016-08-29 | 2017-08-29 | Derivados de n-(piridin-2-il)piridina-sulfonamida y su uso en el tratamiento de enfermedades |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US10450273B2 (enExample) |
| EP (1) | EP3504194B1 (enExample) |
| JP (1) | JP7035055B2 (enExample) |
| KR (1) | KR20190040319A (enExample) |
| CN (1) | CN109641873B (enExample) |
| AR (1) | AR109437A1 (enExample) |
| AU (1) | AU2017319430A1 (enExample) |
| BR (1) | BR112019003883A2 (enExample) |
| CA (1) | CA3031073A1 (enExample) |
| EA (1) | EA201990609A1 (enExample) |
| ES (1) | ES2898069T3 (enExample) |
| MX (1) | MX2019002439A (enExample) |
| TW (1) | TW201811766A (enExample) |
| UY (1) | UY37379A (enExample) |
| WO (1) | WO2018042316A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201811766A (zh) | 2016-08-29 | 2018-04-01 | 瑞士商諾華公司 | N-(吡啶-2-基)吡啶-磺醯胺衍生物及其用於疾病治療之用途 |
| KR102825974B1 (ko) | 2016-09-13 | 2025-06-30 | 삼성디스플레이 주식회사 | 표시 장치 |
| MA53488A (fr) * | 2018-08-31 | 2021-12-08 | Xenon Pharmaceuticals Inc | Composés de sulfonamide substitués par hétéroaryle et leur utilisation en tant qu'inhibiteurs de canaux sodiques |
| US20220033407A1 (en) * | 2018-12-18 | 2022-02-03 | Novartis Ag | N-(pyridin-2-ylsulfonyl)cyclopropanecarboxamide Derivatives and their Use in the Treatment of Disease |
| CA3119656A1 (en) * | 2018-12-21 | 2020-06-25 | Novartis Ag | Macrocyclic compounds and their use in the treatment of disease |
| JP2022519301A (ja) * | 2019-02-06 | 2022-03-22 | ノバルティス アーゲー | Ｎ－（ピリジン－２－イル）ピリジン－スルホンアミド誘導体及び疾患の処置におけるそれらの使用 |
| TWI848092B (zh) | 2019-04-03 | 2024-07-11 | 美商維泰克斯製藥公司 | 囊腫纖維化跨膜傳導調節蛋白調節劑 |
| TWI899097B (zh) | 2019-08-14 | 2025-10-01 | 美商維泰克斯製藥公司 | 製備cftr調節劑之方法 |
| CA3150162A1 (en) | 2019-08-14 | 2021-02-18 | Vertex Pharmaceuticals Incorporated | Crystalline forms of cftr modulators |
| TWI867024B (zh) * | 2019-08-14 | 2024-12-21 | 美商維泰克斯製藥公司 | 囊腫纖維化跨膜傳導調節蛋白之調節劑 |
| CN115003659B (zh) * | 2019-11-12 | 2026-04-21 | 健赞公司 | 用于治疗由cftr活性缺乏介导的疾患的5元杂芳基氨基磺酰胺 |
| EP4058434A1 (en) | 2019-11-12 | 2022-09-21 | Genzyme Corporation | 6-membered heteroarylaminosulfonamides for treating diseases and conditions mediated by deficient cftr activity |
| EP4073021A4 (en) * | 2019-12-13 | 2024-02-28 | Specialty Operations France | PRODUCTION OF BENZENE DERIVATIVES |
| IL300413A (en) | 2020-08-13 | 2023-04-01 | Vertex Pharma | Crystal forms of CFTR modulators |
| KR20230052954A (ko) | 2020-08-20 | 2023-04-20 | 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 | 점액 과다분비를 특징으로 하는 호흡기 질환의 치료 방법 |
| EP4225762A1 (en) | 2020-10-07 | 2023-08-16 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| AU2021397294A1 (en) | 2020-12-10 | 2023-07-06 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
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| WO1996009818A1 (en) | 1994-09-27 | 1996-04-04 | Merck & Co., Inc. | Endothelin receptor antagonists for the treatment of emesis |
| US5939431A (en) * | 1996-06-20 | 1999-08-17 | Schering Corporation | Naphthyridines which affect IL-4 and G-CSF |
| TW520362B (en) | 1996-12-05 | 2003-02-11 | Amgen Inc | Substituted pyrimidine compounds and pharmaceutical composition comprising same |
| SE0102439D0 (sv) | 2001-07-05 | 2001-07-05 | Astrazeneca Ab | New compounds |
| WO2003087044A2 (en) | 2002-04-09 | 2003-10-23 | 7Tm Pharma A/S | Novel carboxamide compounds for use in mch receptor related disorders |
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2017
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- 2017-08-28 US US15/688,089 patent/US10450273B2/en active Active
- 2017-08-28 BR BR112019003883A patent/BR112019003883A2/pt not_active Application Discontinuation
- 2017-08-28 WO PCT/IB2017/055162 patent/WO2018042316A1/en not_active Ceased
- 2017-08-28 ES ES17771589T patent/ES2898069T3/es active Active
- 2017-08-28 EA EA201990609A patent/EA201990609A1/ru unknown
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| US11066369B2 (en) | 2021-07-20 |
| TW201811766A (zh) | 2018-04-01 |
| KR20190040319A (ko) | 2019-04-17 |
| ES2898069T3 (es) | 2022-03-03 |
| BR112019003883A2 (pt) | 2019-06-18 |
| CN109641873B (zh) | 2022-03-18 |
| US10450273B2 (en) | 2019-10-22 |
| MX2019002439A (es) | 2019-07-08 |
| EP3504194A1 (en) | 2019-07-03 |
| UY37379A (es) | 2018-03-23 |
| CN109641873A (zh) | 2019-04-16 |
| EP3504194B1 (en) | 2021-08-18 |
| US20200002281A1 (en) | 2020-01-02 |
| WO2018042316A1 (en) | 2018-03-08 |
| US20180072673A1 (en) | 2018-03-15 |
| EA201990609A1 (ru) | 2019-07-31 |
| CA3031073A1 (en) | 2018-03-08 |
| JP7035055B2 (ja) | 2022-03-14 |
| JP2019530739A (ja) | 2019-10-24 |
| AU2017319430A1 (en) | 2019-02-14 |
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