AU2015208205B2 - Pyrazolo[1,5-a]pyrimidines as antiviral compounds - Google Patents
Pyrazolo[1,5-a]pyrimidines as antiviral compounds Download PDFInfo
- Publication number
- AU2015208205B2 AU2015208205B2 AU2015208205A AU2015208205A AU2015208205B2 AU 2015208205 B2 AU2015208205 B2 AU 2015208205B2 AU 2015208205 A AU2015208205 A AU 2015208205A AU 2015208205 A AU2015208205 A AU 2015208205A AU 2015208205 B2 AU2015208205 B2 AU 2015208205B2
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- AU
- Australia
- Prior art keywords
- pyrimidin
- dimethyl
- dimethoxyphenyl
- pyrazolo
- amine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 183
- 230000000840 anti-viral effect Effects 0.000 title description 5
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 238000011282 treatment Methods 0.000 claims abstract description 27
- 208000036142 Viral infection Diseases 0.000 claims abstract description 19
- 230000009385 viral infection Effects 0.000 claims abstract description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 91
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 84
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 59
- -1 4-dimethylaminophenyl Chemical group 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 39
- 150000002367 halogens Chemical class 0.000 claims description 39
- 125000004429 atom Chemical group 0.000 claims description 34
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- WPFZGADUIUVTCF-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound NC1=CC=NC2=CC=NN12 WPFZGADUIUVTCF-UHFFFAOYSA-N 0.000 claims description 18
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 14
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 14
- 125000002837 carbocyclic group Chemical group 0.000 claims description 13
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- TWCYMPJYRKTZKP-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-n-[(4-methoxyphenyl)methyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=CC(OC)=CC=C1CNC1=CC(C)=NC2=C(C=3C=C(OC)C(OC)=CC=3)C(C)=NN12 TWCYMPJYRKTZKP-UHFFFAOYSA-N 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- CHFHLLRPKVPRKX-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-n-[(4-fluorophenyl)methyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=CC(F)=CC=3)N2N=C1C CHFHLLRPKVPRKX-UHFFFAOYSA-N 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- PLNYJRAFJKJYPQ-UHFFFAOYSA-N 1-[4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]phenyl]ethanone Chemical compound COC=1C=C(C=CC1OC)C=1C(=NN2C1N=C(C=C2NCC2=CC=C(C=C2)C(C)=O)C)C PLNYJRAFJKJYPQ-UHFFFAOYSA-N 0.000 claims description 4
- SBUYZGHVERCOOC-UHFFFAOYSA-N 4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]benzenesulfonamide Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(C=C3)S(N)(=O)=O)N2N=C1C SBUYZGHVERCOOC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- HBVPEDQMSBLKBA-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=CC(Cl)=CC=3)N2N=C1C HBVPEDQMSBLKBA-UHFFFAOYSA-N 0.000 claims description 4
- DKLSLBVMZJPYMK-UHFFFAOYSA-N n-benzyl-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=CC=CC=3)N2N=C1C DKLSLBVMZJPYMK-UHFFFAOYSA-N 0.000 claims description 4
- TXNBLAIOWIQZOL-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[[4-(trifluoromethoxy)phenyl]methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(OC(F)(F)F)C=C3)N2N=C1C TXNBLAIOWIQZOL-UHFFFAOYSA-N 0.000 claims description 3
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 3
- SOXFTPBZGLOGOV-UHFFFAOYSA-N N-[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]-5-methyl-1,3-thiazol-2-amine Chemical compound COC=1C=C(C=CC1OC)C=1C(=NN2C1N=C(C=C2NC=2SC(=CN2)C)C)C SOXFTPBZGLOGOV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 3
- HHJZAOCYINMJSK-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[(2-methylpyrimidin-4-yl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC=1C=C(C=CC1OC)C=1C(=NN2C1N=C(C=C2NCC2=NC(=NC=C2)C)C)C HHJZAOCYINMJSK-UHFFFAOYSA-N 0.000 claims 3
- JBKQNEDBXTWVCM-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[(3-methylsulfonylphenyl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC(=CC=C3)S(C)(=O)=O)N2N=C1C JBKQNEDBXTWVCM-UHFFFAOYSA-N 0.000 claims 3
- IFJUQDKQZZQODR-UHFFFAOYSA-N 4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]phenol Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(O)C=C3)N2N=C1C IFJUQDKQZZQODR-UHFFFAOYSA-N 0.000 claims 3
- GVNJISSYDZPTMJ-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=C4OCOC4=CC=3)N2N=C1C GVNJISSYDZPTMJ-UHFFFAOYSA-N 0.000 claims 3
- XYZQGIPODNTXIL-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[(4-methylsulfonylphenyl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(C=C3)S(C)(=O)=O)N2N=C1C XYZQGIPODNTXIL-UHFFFAOYSA-N 0.000 claims 2
- YVAZHGJQDDGRFS-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[[4-(trifluoromethyl)phenyl]methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(C=C3)C(F)(F)F)N2N=C1C YVAZHGJQDDGRFS-UHFFFAOYSA-N 0.000 claims 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- NUXISAACSNJHDF-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(2-pyridin-2-ylethyl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCCC3=NC=CC=C3)N2N=C1C NUXISAACSNJHDF-UHFFFAOYSA-N 0.000 claims 1
- UYKJTCZRJQLMPM-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(2-pyridin-4-ylethyl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCCC3=CC=NC=C3)N2N=C1C UYKJTCZRJQLMPM-UHFFFAOYSA-N 0.000 claims 1
- IRJQXBJLKRQDLV-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[(1-oxidopyridin-1-ium-4-yl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=[N+]([O-])C=C3)N2N=C1C IRJQXBJLKRQDLV-UHFFFAOYSA-N 0.000 claims 1
- JPGIHFSUHQXYTM-UHFFFAOYSA-N N-(2,3-dihydro-1H-inden-2-yl)-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(C=C2NC1CC2=CC=CC=C2C1)C)C JPGIHFSUHQXYTM-UHFFFAOYSA-N 0.000 claims 1
- LOJCFSSIILNXRK-UHFFFAOYSA-N N-[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]-1,2-oxazol-3-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NC3=NOC=C3)N2N=C1C LOJCFSSIILNXRK-UHFFFAOYSA-N 0.000 claims 1
- FCLOWALYHPZNNC-UHFFFAOYSA-N N-[4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]phenyl]acetamide Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(NC(C)=O)C=C3)N2N=C1C FCLOWALYHPZNNC-UHFFFAOYSA-N 0.000 claims 1
- UNPTYLLVISAIOS-UHFFFAOYSA-N N-[4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]phenyl]methanesulfonamide Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(NS(C)(=O)=O)C=C3)N2N=C1C UNPTYLLVISAIOS-UHFFFAOYSA-N 0.000 claims 1
- 241001144416 Picornavirales Species 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
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Classifications
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- 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
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
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- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
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- Epidemiology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| EP14152202 | 2014-01-22 | ||
| EP14152202.9 | 2014-01-22 | ||
| PCT/EP2015/051177 WO2015110491A2 (en) | 2014-01-22 | 2015-01-21 | Pyrazolo[1,5-a]pyrimidin-7-amine derivatives useful in therapy |
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| AU2015208205A1 AU2015208205A1 (en) | 2016-08-18 |
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| CN110520424B (zh) * | 2017-04-05 | 2022-06-21 | 库洛维公司 | 用于疗法的杂芳族化合物 |
| TWI795510B (zh) * | 2018-01-17 | 2023-03-11 | 英商葛蘭素史密斯克藍智慧財產發展有限公司 | PI4KIIIβ抑制劑 |
| CN108727386A (zh) * | 2018-07-16 | 2018-11-02 | 广州医科大学 | 一种吡唑并嘧啶类化合物及其制备方法和用途 |
| CN118084937A (zh) | 2018-08-21 | 2024-05-28 | 杏林制药株式会社 | 双环杂芳族环衍生物 |
| WO2020074160A1 (en) | 2018-10-10 | 2020-04-16 | Curovir Ab | Condensed pyrimidine or pyridazine derivatives as antiviral agents |
| US12319696B2 (en) * | 2018-10-10 | 2025-06-03 | Curovir Ab | 2,6-dimethyl-n-((pyridin-4-yl)methyl)imidazo[1,2-b]pyridazin-8-amine and 2,5-dimethyl-n-[(pyridin-4-yl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine derivatives for treating viral infections |
| CN109988172B (zh) * | 2019-01-10 | 2020-09-29 | 石家庄学院 | 一种吡唑并[1,5-a]嘧啶类杂环化合物及衍生物的合成方法 |
| WO2021032611A1 (en) | 2019-08-20 | 2021-02-25 | Curovir Ab | Heteroaromatic compounds useful in therapy |
| WO2024184442A1 (en) | 2023-03-09 | 2024-09-12 | Curovir Ab | Compound and formulation for systemic therapy by oral transmucosal administration |
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| US8633198B1 (en) * | 2011-09-20 | 2014-01-21 | Nant Holdings Ip, Llc | Small molecule inhibitors of influenza A RNA-dependent RNA polymerase |
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| CA2107479C (en) * | 1991-04-22 | 1997-12-16 | Makoto Inoue | Pyrazolo[1,5-a]pyrimidine derivatives and anti-inflammatory agent containing the same |
| US6313124B1 (en) | 1997-07-23 | 2001-11-06 | Dupont Pharmaceuticals Company | Tetrazine bicyclic compounds |
| US6372743B1 (en) * | 1999-09-30 | 2002-04-16 | Neurogen Corporation | Certain alkylene diamine-substituted pyrazlo (1,5-a)-1,5-pyrimidines and pyrazolo (1,5-a) 1,3,5-triazines |
| WO2003095455A2 (en) * | 2002-05-10 | 2003-11-20 | Smithkline Beecham Corporation | Substituted pyrazolopyrimidines |
| MY145332A (en) * | 2002-09-04 | 2012-01-31 | Schering Corp | Trisubstituted 4-aminopyrazolopyrimidines as cyclin dependent kinase inhibitors |
| US7601724B2 (en) * | 2002-09-04 | 2009-10-13 | Schering Corporation | Substituted pyrazolo[1,5-a]pyrimidines as protein kinase inhibitors |
| GB0519957D0 (en) * | 2005-09-30 | 2005-11-09 | Sb Pharmco Inc | Chemical compound |
| WO2010086040A1 (en) | 2009-01-29 | 2010-08-05 | Biomarin Iga, Ltd. | Pyrazolo-pyrimidines for treatment of duchenne muscular dystrophy |
| CA2791166C (en) * | 2010-02-26 | 2014-12-30 | Mitsubishi Tanabe Pharma Corporation | Pyrazolopyrimidine compounds and their use as pde10 inhibitors |
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| US8633198B1 (en) * | 2011-09-20 | 2014-01-21 | Nant Holdings Ip, Llc | Small molecule inhibitors of influenza A RNA-dependent RNA polymerase |
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| AU2015208205A1 (en) | 2016-08-18 |
| EP3096762C0 (en) | 2023-06-28 |
| CA2935658A1 (en) | 2015-07-30 |
| WO2015110491A2 (en) | 2015-07-30 |
| US20160318937A1 (en) | 2016-11-03 |
| US9963455B2 (en) | 2018-05-08 |
| CN106061975A (zh) | 2016-10-26 |
| ES2954126T3 (es) | 2023-11-20 |
| EP3096762B1 (en) | 2023-06-28 |
| CA2935658C (en) | 2023-02-21 |
| NZ722290A (en) | 2021-08-27 |
| CN106061975B (zh) | 2019-09-24 |
| EP3096762A2 (en) | 2016-11-30 |
| RU2689788C2 (ru) | 2019-05-29 |
| BR112016016798B1 (pt) | 2022-06-28 |
| BR112016016798A2 (enExample) | 2017-08-08 |
| JP6509238B2 (ja) | 2019-05-08 |
| RU2016134130A (ru) | 2018-02-26 |
| ZA201605666B (en) | 2021-01-27 |
| WO2015110491A3 (en) | 2015-09-17 |
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