EA038421B1 - Соединения, ингибирующие металлоферменты - Google Patents
Соединения, ингибирующие металлоферменты Download PDFInfo
- Publication number
- EA038421B1 EA038421B1 EA201891539A EA201891539A EA038421B1 EA 038421 B1 EA038421 B1 EA 038421B1 EA 201891539 A EA201891539 A EA 201891539A EA 201891539 A EA201891539 A EA 201891539A EA 038421 B1 EA038421 B1 EA 038421B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- phenyl
- pyridin
- difluoro
- piperazin
- hydroxy
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 357
- 229940125956 metalloenzyme inhibitor Drugs 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 136
- 238000000034 method Methods 0.000 claims abstract description 76
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- 208000035475 disorder Diseases 0.000 claims abstract description 65
- 230000000694 effects Effects 0.000 claims abstract description 32
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 278
- -1 1-tetrazolyl Chemical group 0.000 claims description 264
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 176
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 125
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 76
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- 238000011282 treatment Methods 0.000 claims description 41
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- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 239000004562 water dispersible granule Substances 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 235000015099 wheat brans Nutrition 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- A61K31/4439—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- 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
-
- 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
-
- 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
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562273167P | 2015-12-30 | 2015-12-30 | |
| PCT/US2016/069217 WO2017117393A1 (en) | 2015-12-30 | 2016-12-29 | Metalloenzyme inhibitor compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201891539A1 EA201891539A1 (ru) | 2018-12-28 |
| EA038421B1 true EA038421B1 (ru) | 2021-08-26 |
Family
ID=59225927
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201891539A EA038421B1 (ru) | 2015-12-30 | 2016-12-29 | Соединения, ингибирующие металлоферменты |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US10464922B2 (https=) |
| EP (1) | EP3397629B1 (https=) |
| JP (1) | JP6803923B2 (https=) |
| KR (1) | KR102240920B1 (https=) |
| CN (1) | CN108779094B (https=) |
| AU (1) | AU2016380349B2 (https=) |
| BR (1) | BR112018013522A2 (https=) |
| CA (1) | CA3006469C (https=) |
| EA (1) | EA038421B1 (https=) |
| MX (1) | MX376201B (https=) |
| TW (1) | TWI623528B (https=) |
| WO (1) | WO2017117393A1 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015143184A1 (en) | 2014-03-19 | 2015-09-24 | Viamet Pharmaceuticals, Inc. | Antifungal compound process |
| EP3119753B1 (en) | 2014-03-19 | 2020-11-04 | Dow AgroSciences LLC | 2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-substituted-pyridin-2-yl)-3-(1h-tetrazol-1-yl)propan-2-ols and processes for their preparation |
| JP6606508B2 (ja) | 2014-03-19 | 2019-11-13 | マイコヴィア ファーマシューティカルズ，インコーポレイテッド | 抗真菌化合物の調製方法 |
| KR102441243B1 (ko) | 2014-03-19 | 2022-09-07 | 브이피에스-3, 엘엘씨 | 2-(2,4-디플루오르페닐)-1,1-디플루오르-1-(5-치환된-피리딘-2-일)-3-(1h-테트라졸-1-일)프로판-2-올 및 이의 제조방법 |
| CN109970629B (zh) | 2014-03-19 | 2023-04-11 | 迈科维亚医药公司 | 抗真菌化合物的制备方法 |
| AU2015231275B2 (en) | 2014-03-19 | 2019-03-07 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| JP2017509646A (ja) | 2014-03-19 | 2017-04-06 | ヴィアメット ファーマスーティカルズ，インコーポレイテッド | 抗真菌化合物の調製方法 |
| AU2015231216B2 (en) | 2014-03-19 | 2019-04-04 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| CA2942936A1 (en) | 2014-03-19 | 2015-09-24 | Viamet Pharmaceuticals, Inc. | Antifungal compound process |
| CN108289457B (zh) | 2015-09-18 | 2021-08-06 | 迈科维亚医药公司 | 抗真菌化合物制备方法 |
| WO2019182743A1 (en) * | 2018-03-20 | 2019-09-26 | Innocrin Pharmaceuticals, Inc. | Compositions for the treatment of brain tumors |
| US12357615B2 (en) | 2018-10-11 | 2025-07-15 | Kembi Therapeutics Pty Ltd | Compositions for the treatment of brain tumors |
| WO2022216680A1 (en) | 2021-04-05 | 2022-10-13 | Halia Therapeutics, Inc. | Nek7 inhibitors |
| CN113444131B (zh) * | 2021-06-24 | 2022-10-21 | 鲁东大学 | N-乙酰氨基葡萄糖类化合物及其制备方法和应用 |
| US20250270193A1 (en) * | 2021-10-20 | 2025-08-28 | Ohio State Innovation Foundation | Arylimidamides for use in treatment of cancers |
| CN115466227B (zh) * | 2022-06-30 | 2024-07-19 | 杭州国瑞生物科技有限公司 | 一种3-(氯甲基)-1-甲基-1h-1,2,4-三唑盐酸盐的制备方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000064927A1 (en) * | 1999-04-27 | 2000-11-02 | Fujisawa Pharmaceutical Co., Ltd. | Cyclic hexapeptides having antibiotic activity |
| US20020049194A1 (en) * | 1994-06-15 | 2002-04-25 | Hidenori Ogawa | Benzoheterocyclic derivatives |
| US20110244004A1 (en) * | 2001-04-03 | 2011-10-06 | Schering-Plough Corporation | Antifungal composition with enhanced bioavailability |
| US20140155387A1 (en) * | 2011-04-21 | 2014-06-05 | Qurient, Co. Ltd. | Anti-Inflammation Compounds |
| WO2015143137A1 (en) * | 2014-03-19 | 2015-09-24 | Viamet Pharmaceuticals, Inc. | Antifungal compound process |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5087240A (en) | 1983-08-18 | 1992-02-11 | Drug Delivery Systems Inc. | Transdermal drug patch with conductive fibers |
| US4921475A (en) | 1983-08-18 | 1990-05-01 | Drug Delivery Systems Inc. | Transdermal drug patch with microtubes |
| US4738851A (en) | 1985-09-27 | 1988-04-19 | University Of Iowa Research Foundation, Inc. | Controlled release ophthalmic gel formulation |
| US5163899A (en) | 1987-03-20 | 1992-11-17 | Drug Delivery Systems Inc. | Transdermal drug delivery system |
| US5312325A (en) | 1987-05-28 | 1994-05-17 | Drug Delivery Systems Inc | Pulsating transdermal drug delivery system |
| GB8804164D0 (en) | 1988-02-23 | 1988-03-23 | Tucker J M | Bandage for administering physiologically active compound |
| US4882150A (en) | 1988-06-03 | 1989-11-21 | Kaufman Herbert E | Drug delivery system |
| US5008110A (en) | 1988-11-10 | 1991-04-16 | The Procter & Gamble Company | Storage-stable transdermal patch |
| US5088977A (en) | 1988-12-21 | 1992-02-18 | Drug Delivery Systems Inc. | Electrical transdermal drug applicator with counteractor and method of drug delivery |
| US5521222A (en) | 1989-09-28 | 1996-05-28 | Alcon Laboratories, Inc. | Topical ophthalmic pharmaceutical vehicles |
| DK0431519T3 (da) | 1989-12-04 | 1994-07-04 | Searle & Co | System til transdermal indgivelse af albuterol |
| US5077033A (en) | 1990-08-07 | 1991-12-31 | Mediventures Inc. | Ophthalmic drug delivery with thermo-irreversible gels of polxoxyalkylene polymer and ionic polysaccharide |
| JP2594486B2 (ja) | 1991-01-15 | 1997-03-26 | アルコン ラボラトリーズ インコーポレイテッド | 局所的眼薬組成物 |
| US5352456A (en) | 1991-10-10 | 1994-10-04 | Cygnus Therapeutic Systems | Device for administering drug transdermally which provides an initial pulse of drug |
| DE69228827T2 (de) | 1991-12-18 | 1999-10-21 | Minnesota Mining And Mfg. Co., Saint Paul | Mehrschichtige sperrstrukturen |
| ATE132381T1 (de) | 1992-01-29 | 1996-01-15 | Voelkl Franz Ski | Ballspielschläger, insbesondere tennisschläger |
| IL114193A (en) | 1994-06-20 | 2000-02-29 | Teva Pharma | Ophthalmic pharmaceutical compositions based on sodium alginate |
| ES2094688B1 (es) | 1994-08-08 | 1997-08-01 | Cusi Lab | Manoemulsion del tipo de aceite en agua, util como vehiculo oftalmico y procedimiento para su preparacion. |
| IT1283911B1 (it) | 1996-02-05 | 1998-05-07 | Farmigea Spa | Soluzioni oftalmiche viscosizzate con polisaccaridi della gomma di tamarindo |
| US5800807A (en) | 1997-01-29 | 1998-09-01 | Bausch & Lomb Incorporated | Ophthalmic compositions including glycerin and propylene glycol |
| US6261547B1 (en) | 1998-04-07 | 2001-07-17 | Alcon Manufacturing, Ltd. | Gelling ophthalmic compositions containing xanthan gum |
| US6197934B1 (en) | 1998-05-22 | 2001-03-06 | Collagenesis, Inc. | Compound delivery using rapidly dissolving collagen film |
| AU2011242562B2 (en) * | 2010-04-24 | 2016-10-13 | Mycovia Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| US9414596B2 (en) * | 2012-01-20 | 2016-08-16 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| WO2013109998A1 (en) | 2012-01-20 | 2013-07-25 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| AU2014278172B2 (en) * | 2013-06-12 | 2018-08-09 | Mycovia Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
-
2016
- 2016-12-29 EA EA201891539A patent/EA038421B1/ru unknown
- 2016-12-29 WO PCT/US2016/069217 patent/WO2017117393A1/en not_active Ceased
- 2016-12-29 MX MX2018008105A patent/MX376201B/es active IP Right Grant
- 2016-12-29 JP JP2018553846A patent/JP6803923B2/ja not_active Expired - Fee Related
- 2016-12-29 BR BR112018013522A patent/BR112018013522A2/pt not_active Application Discontinuation
- 2016-12-29 CA CA3006469A patent/CA3006469C/en active Active
- 2016-12-29 US US16/066,763 patent/US10464922B2/en not_active Expired - Fee Related
- 2016-12-29 AU AU2016380349A patent/AU2016380349B2/en not_active Ceased
- 2016-12-29 EP EP16882663.4A patent/EP3397629B1/en active Active
- 2016-12-29 KR KR1020187022077A patent/KR102240920B1/ko not_active Expired - Fee Related
- 2016-12-29 CN CN201680076973.0A patent/CN108779094B/zh not_active Expired - Fee Related
- 2016-12-30 TW TW105144241A patent/TWI623528B/zh not_active IP Right Cessation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020049194A1 (en) * | 1994-06-15 | 2002-04-25 | Hidenori Ogawa | Benzoheterocyclic derivatives |
| WO2000064927A1 (en) * | 1999-04-27 | 2000-11-02 | Fujisawa Pharmaceutical Co., Ltd. | Cyclic hexapeptides having antibiotic activity |
| US20110244004A1 (en) * | 2001-04-03 | 2011-10-06 | Schering-Plough Corporation | Antifungal composition with enhanced bioavailability |
| US20140155387A1 (en) * | 2011-04-21 | 2014-06-05 | Qurient, Co. Ltd. | Anti-Inflammation Compounds |
| WO2015143137A1 (en) * | 2014-03-19 | 2015-09-24 | Viamet Pharmaceuticals, Inc. | Antifungal compound process |
Non-Patent Citations (1)
| Title |
|---|
| PEQUEUX, C. et al. Oxytocin Synthesis and Oxytocin Receptor Expression by Cell Lines of Human Small Cell Carcinoma of the Lung Stimulate Tumor Growth through Autocrine/Paracrine Signaling. Cancer Research, Vol. 62, 15 August 2002, p. 4623-4629; abstract * |
Also Published As
| Publication number | Publication date |
|---|---|
| CA3006469C (en) | 2023-01-10 |
| EP3397629B1 (en) | 2023-04-19 |
| TW201734000A (zh) | 2017-10-01 |
| MX2018008105A (es) | 2018-11-12 |
| CN108779094B (zh) | 2021-11-16 |
| JP6803923B2 (ja) | 2020-12-23 |
| EA201891539A1 (ru) | 2018-12-28 |
| BR112018013522A2 (pt) | 2018-12-11 |
| KR20180099845A (ko) | 2018-09-05 |
| AU2016380349A1 (en) | 2018-06-14 |
| EP3397629A4 (en) | 2019-06-05 |
| MX376201B (es) | 2025-03-07 |
| CN108779094A (zh) | 2018-11-09 |
| JP2019502755A (ja) | 2019-01-31 |
| US20190016700A1 (en) | 2019-01-17 |
| WO2017117393A1 (en) | 2017-07-06 |
| EP3397629A1 (en) | 2018-11-07 |
| US10464922B2 (en) | 2019-11-05 |
| TWI623528B (zh) | 2018-05-11 |
| AU2016380349B2 (en) | 2020-10-29 |
| KR102240920B1 (ko) | 2021-04-16 |
| CA3006469A1 (en) | 2017-07-06 |
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