JP6748652B2 - 抗酸化性炎症調節剤としてのイミダゾリル三環式エノン - Google Patents
抗酸化性炎症調節剤としてのイミダゾリル三環式エノン Download PDFInfo
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- JP6748652B2 JP6748652B2 JP2017542001A JP2017542001A JP6748652B2 JP 6748652 B2 JP6748652 B2 JP 6748652B2 JP 2017542001 A JP2017542001 A JP 2017542001A JP 2017542001 A JP2017542001 A JP 2017542001A JP 6748652 B2 JP6748652 B2 JP 6748652B2
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- 0 CC(C(CC1)C(C)(C=C2C#N)c3c1[n](*)c(*)n3)C2=O Chemical compound CC(C(CC1)C(C)(C=C2C#N)c3c1[n](*)c(*)n3)C2=O 0.000 description 2
- HKKJRHKPSQDJCV-ZLUWISGCSA-N CC(NC1=C2CC[C@@H]([C@@H]3C)[C@]1(C)C=C(C(N)=O)C3=O)N2c1ccccc1 Chemical compound CC(NC1=C2CC[C@@H]([C@@H]3C)[C@]1(C)C=C(C(N)=O)C3=O)N2c1ccccc1 HKKJRHKPSQDJCV-ZLUWISGCSA-N 0.000 description 1
- ZVVBRNFAAXHDAL-FJQAWONWSA-N C[C@@H](C(CC1)[C@](C)(C=C2C#N)c(nc3C)c1[n]3-c1ccc(C3C=CC=CC3)cc1)C2O Chemical compound C[C@@H](C(CC1)[C@](C)(C=C2C#N)c(nc3C)c1[n]3-c1ccc(C3C=CC=CC3)cc1)C2O ZVVBRNFAAXHDAL-FJQAWONWSA-N 0.000 description 1
- RVTWWRICOMNHPX-WNYYYEPTSA-N C[C@@H]([C@H](CC1)C(C)(C=C2C#N)c(nc3/C(/C=C\C#C)=C/C)c1[n]3-c1n[n](C)nn1)C2=O Chemical compound C[C@@H]([C@H](CC1)C(C)(C=C2C#N)c(nc3/C(/C=C\C#C)=C/C)c1[n]3-c1n[n](C)nn1)C2=O RVTWWRICOMNHPX-WNYYYEPTSA-N 0.000 description 1
- FNXSTDTYCQYDNA-WDDWZANVSA-N C[C@@H]([C@H](CC1)[C@@H](CCC=C2C#N)c3c1[n](Cc1ccccc1)c(CCOCc1ccccc1)n3)C2=O Chemical compound C[C@@H]([C@H](CC1)[C@@H](CCC=C2C#N)c3c1[n](Cc1ccccc1)c(CCOCc1ccccc1)n3)C2=O FNXSTDTYCQYDNA-WDDWZANVSA-N 0.000 description 1
- MCHYPBDJVSZMBO-KFSOKAEPSA-N C[C@@H]([C@H](CC1)[C@](C)(C=C2C#N)c(nc3-c4c[n](C)nc4)c1[n]3-c1ccccc1)C2=O Chemical compound C[C@@H]([C@H](CC1)[C@](C)(C=C2C#N)c(nc3-c4c[n](C)nc4)c1[n]3-c1ccccc1)C2=O MCHYPBDJVSZMBO-KFSOKAEPSA-N 0.000 description 1
- GLLBIWLYPZJREM-AKUOWQNMSA-N C[C@@H]([C@H](CC1)[C@](C)(C=C2C#N)c(nc3-c4ccccc4)c1[n]3-c1cccc(CCC[O](C)C(C)=O)c1)C2=O Chemical compound C[C@@H]([C@H](CC1)[C@](C)(C=C2C#N)c(nc3-c4ccccc4)c1[n]3-c1cccc(CCC[O](C)C(C)=O)c1)C2=O GLLBIWLYPZJREM-AKUOWQNMSA-N 0.000 description 1
- CBMYUCMJPHXXTK-SOJACNMYSA-N C[C@@H]([C@H](CC1)[C@](C)(C=C2C#N)c(nc3C)c1[n]3-c1cccc(CCC(OC)=O)c1)C2=O Chemical compound C[C@@H]([C@H](CC1)[C@](C)(C=C2C#N)c(nc3C)c1[n]3-c1cccc(CCC(OC)=O)c1)C2=O CBMYUCMJPHXXTK-SOJACNMYSA-N 0.000 description 1
- OMZPGFZQTRBKMQ-PGXXELPDSA-N C[C@@H]([C@H](CCC(C1N=C2C)N2c2cccc(CCC(N(C)C)=O)c2)[C@]1(C)C=C1C#N)C1=O Chemical compound C[C@@H]([C@H](CCC(C1N=C2C)N2c2cccc(CCC(N(C)C)=O)c2)[C@]1(C)C=C1C#N)C1=O OMZPGFZQTRBKMQ-PGXXELPDSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/10—Radicals substituted by halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D403/04—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
-
- 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
- C07D403/10—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 carbon chain containing aromatic 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
- C07D403/14—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
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)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562115247P | 2015-02-12 | 2015-02-12 | |
| US62/115,247 | 2015-02-12 | ||
| PCT/US2016/017769 WO2016130927A1 (en) | 2015-02-12 | 2016-02-12 | Imidazolyl tricyclic enones as antioxidant iflammation modulators |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018505196A JP2018505196A (ja) | 2018-02-22 |
| JP2018505196A5 JP2018505196A5 (https=) | 2019-03-22 |
| JP6748652B2 true JP6748652B2 (ja) | 2020-09-02 |
Family
ID=55442884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017542001A Active JP6748652B2 (ja) | 2015-02-12 | 2016-02-12 | 抗酸化性炎症調節剤としてのイミダゾリル三環式エノン |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US11059792B2 (https=) |
| EP (1) | EP3256451B1 (https=) |
| JP (1) | JP6748652B2 (https=) |
| KR (2) | KR102686868B1 (https=) |
| CN (1) | CN107428698B (https=) |
| AU (1) | AU2016219109B2 (https=) |
| CA (1) | CA2974726C (https=) |
| EA (1) | EA038328B1 (https=) |
| IL (1) | IL253923B (https=) |
| MX (1) | MX370586B (https=) |
| NZ (1) | NZ734292A (https=) |
| WO (1) | WO2016130927A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009129546A1 (en) | 2008-04-18 | 2009-10-22 | Reata Pharmaceuticals, Inc. | Antioxidant inflammation modulators: oleanolic acid derivatives with amino and other modifications at c-17 |
| JP6410710B2 (ja) | 2012-04-27 | 2018-10-24 | リアタ ファーマシューティカルズ インコーポレイテッド | バルドキソロンメチルの２，２−ジフルオロプロピオンアミド誘導体、その多形体および使用方法 |
| US9512094B2 (en) | 2012-09-10 | 2016-12-06 | Reata Pharmaceuticals, Inc. | C17-heteroaryl derivatives of oleanolic acid and methods of use thereof |
| TWI649330B (zh) | 2013-04-24 | 2019-02-01 | 艾伯維有限公司 | 甲基巴多索龍之２，２－二氟丙醯胺衍生物、其多晶形及其使用方法 |
| TWI831738B (zh) | 2016-12-16 | 2024-02-11 | 美商瑞塔醫藥有限責任公司 | 用於抑制ＲＯＲγ及其他用途的嘧啶三環烯酮衍生物 |
| IL279348B2 (en) * | 2018-06-15 | 2026-01-01 | Reata Pharmaceuticals Inc | Decahydro-2h-naphth[1,2-d]imidazole compounds for inhibition of IL-17 and ROR-gamma |
| WO2019246461A1 (en) * | 2018-06-20 | 2019-12-26 | Reata Pharmaceuticals, Inc. | Cysteine-dependent inverse agonists of nuclear receptors ror-gamma/ror-gamma-t and methods of treating diseases or disorders therewith |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6326507B1 (en) | 1998-06-19 | 2001-12-04 | Trustees Of Dartmouth College | Therapeutic compounds and methods of use |
| US7435755B2 (en) | 2000-11-28 | 2008-10-14 | The Trustees Of Dartmouth College | CDDO-compounds and combination therapies thereof |
| CA2430454A1 (en) | 2000-11-28 | 2002-06-20 | Board Of Regents, The University Of Texas System | Cddo-compounds and combination therapies thereof |
| DK1465615T3 (da) | 2002-01-15 | 2012-11-12 | Dartmouth College | Tricykliske bisenonderivater og fremgangsmåder til anvendelse heraf |
| AU2003303128A1 (en) | 2002-05-13 | 2004-08-13 | Trustees Of Dartmouth College | Inhibitors and methods of use thereof |
| WO2006089406A1 (en) | 2005-02-22 | 2006-08-31 | Gemin X Biotechnologies Inc. | Diterpenoid compounds, compositions thereof and their use as anti-cancer or anti-fungal agents |
| US8921340B2 (en) | 2006-11-17 | 2014-12-30 | Trustees Of Dartmouth College | Methods for using synthetic triterpenoids in the treatment of bone or cartilage diseases or conditions |
| US7714012B2 (en) | 2006-11-17 | 2010-05-11 | Trustees Of Dartmouth University | Synthesis and biological activities of new tricyclic-bis-enones (TBEs) |
| US8299046B2 (en) | 2006-11-17 | 2012-10-30 | Trustees Of Dartmouth College | Synthetic triterpenoids and tricyclic-bis-enones for use in stimulating bone and cartilage growth |
| WO2008136838A1 (en) | 2007-05-04 | 2008-11-13 | Trustees Of Dartmouth College | Novel amide derivatives of cddo and methods of use thereof |
| US20090048205A1 (en) | 2007-08-15 | 2009-02-19 | Colin Meyer | Combination therapy with synthetic triterpenoids and gemcitabine |
| US8088824B2 (en) | 2007-08-15 | 2012-01-03 | Reata Pharmaceuticals Inc. | Forms of CDDO methyl ester |
| PL2252283T3 (pl) | 2008-01-11 | 2019-09-30 | Reata Pharmaceuticals, Inc. | Syntetyczne triterpenoidy i sposoby zastosowania w leczeniu choroby |
| CA2721665C (en) | 2008-04-18 | 2017-01-24 | Reata Pharmaceuticals, Inc. | Compounds including an anti-inflammatory pharmacore and methods of use |
| CN102164941B (zh) | 2008-04-18 | 2015-05-27 | 里亚塔医药公司 | 抗氧化剂炎症调节剂:具有饱和c环的齐墩果酸衍生物 |
| RS55631B1 (sr) | 2008-04-18 | 2017-06-30 | Reata Pharmaceuticals Inc | Antioksidansni modulatori upale: c-17 homologisani derivati oleanolinske kiseline |
| WO2009129546A1 (en) | 2008-04-18 | 2009-10-22 | Reata Pharmaceuticals, Inc. | Antioxidant inflammation modulators: oleanolic acid derivatives with amino and other modifications at c-17 |
| WO2009146216A2 (en) | 2008-04-18 | 2009-12-03 | Reata Pharmaceuticals. Inc. | Antioxidant inflammation modulators: novel derivatives of oleanolic acid |
| ES2449396T3 (es) | 2008-07-22 | 2014-03-19 | Trustees Of Dartmouth College | Cianoenonas monocíclicas y métodos de uso de las mismas |
| WO2010053817A1 (en) | 2008-11-04 | 2010-05-14 | Trustees Of Dartmouth College | Betulinic acid derivatives and methods of use thereof |
| SMT201900432T1 (it) | 2009-02-13 | 2019-09-09 | Reata Pharmaceuticals Inc | Composizioni di dosaggio orali, a rilascio ritardato contenenti cddo-me amorfo |
| MX357596B (es) | 2010-04-12 | 2018-07-16 | Reata Pharmaceuticals Inc | Método para tratar obesidad utilizando moduladores de inflamación con antioxidantes. |
| PL2651902T3 (pl) * | 2010-12-17 | 2018-04-30 | Reata Pharmaceuticals, Inc. | Pirazolilowe i pirymidynylowe tricykliczne enony jako modulatory zapalenia o działaniu przeciwutleniającym |
| SI2683731T1 (sl) | 2011-03-11 | 2019-07-31 | Reata Pharmaceuticals, Inc. | C4-monometil triterpenoidni derivati in postopki njihove uporabe |
| JP6410710B2 (ja) | 2012-04-27 | 2018-10-24 | リアタ ファーマシューティカルズ インコーポレイテッド | バルドキソロンメチルの２，２−ジフルオロプロピオンアミド誘導体、その多形体および使用方法 |
| WO2013188818A1 (en) | 2012-06-15 | 2013-12-19 | Reata Pharmaceuticals, Inc. | A-ring epoxidized triterpenoid-based anti-inflammation modulators and methods of use thereof |
| US9512094B2 (en) | 2012-09-10 | 2016-12-06 | Reata Pharmaceuticals, Inc. | C17-heteroaryl derivatives of oleanolic acid and methods of use thereof |
| WO2014040060A1 (en) | 2012-09-10 | 2014-03-13 | Reata Pharmaceuticals, Inc. | C17-alkanediyl and alkenediyl derivatives of oleanolic acid and methods of use thereof |
| US20140088163A1 (en) | 2012-09-10 | 2014-03-27 | Reata Pharmaceuticals, Inc. | C17-heteroaryl derivatives of oleanolic acid and methods of use thereof |
| US9278912B2 (en) | 2012-09-10 | 2016-03-08 | Reata Pharmaceuticals, Inc. | C13-hydroxy derivatives of oleanolic acid and methods of use thereof |
| BR112016003454B1 (pt) | 2013-08-23 | 2023-02-14 | Reata Pharmaceuticals, Inc. | Uso de composto de metil bardoxolona |
| JP6530758B2 (ja) | 2014-01-24 | 2019-06-12 | リアタ ファーマシューティカルズ，インク | 抗酸化性炎症調節剤としてのアリールおよびアリールアルキル置換されたピラゾリルおよびピリミジニル三環式エノン類 |
| TWI831738B (zh) * | 2016-12-16 | 2024-02-11 | 美商瑞塔醫藥有限責任公司 | 用於抑制ＲＯＲγ及其他用途的嘧啶三環烯酮衍生物 |
-
2016
- 2016-02-12 CN CN201680011160.3A patent/CN107428698B/zh active Active
- 2016-02-12 MX MX2017010422A patent/MX370586B/es active IP Right Grant
- 2016-02-12 AU AU2016219109A patent/AU2016219109B2/en active Active
- 2016-02-12 KR KR1020177023589A patent/KR102686868B1/ko active Active
- 2016-02-12 WO PCT/US2016/017769 patent/WO2016130927A1/en not_active Ceased
- 2016-02-12 KR KR1020247004058A patent/KR20240035818A/ko not_active Ceased
- 2016-02-12 JP JP2017542001A patent/JP6748652B2/ja active Active
- 2016-02-12 NZ NZ734292A patent/NZ734292A/en unknown
- 2016-02-12 EA EA201791814A patent/EA038328B1/ru unknown
- 2016-02-12 US US15/548,909 patent/US11059792B2/en active Active
- 2016-02-12 EP EP16706722.2A patent/EP3256451B1/en active Active
- 2016-02-12 CA CA2974726A patent/CA2974726C/en active Active
-
2017
- 2017-08-09 IL IL253923A patent/IL253923B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| KR20240035818A (ko) | 2024-03-18 |
| CN107428698B (zh) | 2021-10-26 |
| BR112017017133A2 (pt) | 2018-04-03 |
| US20180127380A1 (en) | 2018-05-10 |
| KR20170117092A (ko) | 2017-10-20 |
| CA2974726A1 (en) | 2016-08-18 |
| NZ734292A (en) | 2022-09-30 |
| IL253923B (en) | 2021-06-30 |
| MX370586B (es) | 2019-12-17 |
| MX2017010422A (es) | 2018-06-06 |
| EA201791814A1 (ru) | 2017-12-29 |
| US11059792B2 (en) | 2021-07-13 |
| EA038328B1 (ru) | 2021-08-10 |
| KR102686868B1 (ko) | 2024-07-19 |
| AU2016219109B2 (en) | 2020-05-14 |
| WO2016130927A1 (en) | 2016-08-18 |
| EP3256451B1 (en) | 2021-10-20 |
| CA2974726C (en) | 2023-09-19 |
| EP3256451A1 (en) | 2017-12-20 |
| JP2018505196A (ja) | 2018-02-22 |
| AU2016219109A1 (en) | 2017-08-24 |
| IL253923A0 (en) | 2017-10-31 |
| CN107428698A (zh) | 2017-12-01 |
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