AR107512A1 - Triterpenoides modificados en c-3 y c-17 como inhibidores del vih-1 - Google Patents
Triterpenoides modificados en c-3 y c-17 como inhibidores del vih-1Info
- Publication number
- AR107512A1 AR107512A1 ARP170100255A ARP170100255A AR107512A1 AR 107512 A1 AR107512 A1 AR 107512A1 AR P170100255 A ARP170100255 A AR P170100255A AR P170100255 A ARP170100255 A AR P170100255A AR 107512 A1 AR107512 A1 AR 107512A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- substituted
- group
- heteroaryl
- cycloalkyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 title 1
- 150000003648 triterpenes Chemical class 0.000 title 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 24
- 125000000217 alkyl group Chemical group 0.000 abstract 14
- 125000001072 heteroaryl group Chemical group 0.000 abstract 11
- 125000003118 aryl group Chemical group 0.000 abstract 6
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 5
- 150000001875 compounds Chemical class 0.000 abstract 4
- -1 -fluoroalkyl C1−6 Chemical group 0.000 abstract 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 3
- 208000030507 AIDS Diseases 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 230000000840 anti-viral effect Effects 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 abstract 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 abstract 1
- 230000035800 maturation Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
Classifications
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- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
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- 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
-
- 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
- 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
- C07D417/02—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 two hetero rings
- C07D417/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/503—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses
- C12N9/506—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses derived from RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/52—Ortho- or ortho- and peri-condensed systems containing five condensed rings
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16211—Human Immunodeficiency Virus, HIV concerning HIV gagpol
- C12N2740/16222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Se exponen compuestos que tienen propiedades farmacológicas y que afectan a la bioactividad, sus composiciones farmacéuticas y procedimientos de uso. En particular, se proporcionan derivados de ácido botulínico que poseen actividad antivírica única como inhibidores de la maduración del VIH. Estos compuestos son útiles para el tratamiento del VIH y del sida. Reivindicación 1: Un compuesto de fórmula (1), incluyendo sales farmacéuticamente aceptables del mismo, en la que R¹ es isopropenilo o isopropilo; A es -alquil C₁₋₆-O-R⁰; en donde R⁰ es heteroaril-Q⁰; Q⁰ se selecciona del grupo de -H, -CN, -alquilo C₁₋₆, -COOH, -Ph, -O-alquilo C₁₋₆, -halo, -CF₃; Y se selecciona del grupo de -COOR², -C(O)NR²SO₂R³, -C(O)NHSO₂NR²R², -SO₂NR²C(O)R², -tetrazol y -CONHOH; en donde n = 1 - 6; R² es -H, -alquilo C₁₋₆, -alquilo C₁₋₆ sustituido con alquilo o -alquilo C₁₋₆ sustituido con arilo; W está ausente o es -CH₂- o -CO-; R³ es -H, -alquilo C₁₋₆ o -alquilo C₁₋₆ sustituido con alquilo; R⁴ se selecciona del grupo de -H, -alquilo C₁₋₆, -alquil C₁₋₆-cicloalquilo C₃₋₆, -alquilo C₁₋₆ sustituido con C₁₋₆, -alquil C₁₋₆-Q¹, -alquil C₁₋₆-cicloalquil C₃₋₆-Q¹, arilo, heteroarilo, heteroarilo sustituido, -COR⁶, -SO₂R⁷, -SO₂NR²R² y un compuesto de fórmula (2) ó (3), en las que G se selecciona del grupo de -O-, -SO₂- y -NR¹²-; en las que Q¹ se selecciona del grupo de -alquilo C₁₋₆, -fluoroalquilo C₁₋₆, heteroarilo, heteroarilo sustituido, halógeno, -CF₃, -OR², -COOR², -NR⁸R⁹, -CONR⁸R⁹ y -SO₂R⁷; R⁵ se selecciona del grupo de -H, -alquilo C₁₋₆, -cicloalquilo C₃₋₆, -alquilo C₁₋₆ sustituido con alquilo, -alquil C₁₋₆-NR⁸R⁹, -COR³, -SO₂R⁷ y -SO₂NR²R²; con la condición de que R⁴ o R⁵ no sean -COR⁶ cuando W sea -CO-; con la condición adicional de que únicamente uno de R⁴ o R⁵ se selecciona entre el grupo de -COR⁶, -COCOR⁶, -SO₂R⁷ y -SO₂NR²R²; R⁶ se selecciona del grupo de -H, -alquilo C₁₋₆, -alquilo C₁₋₆ sustituido con alquilo, -cicloalquilo C₃₋₆, -cicloalquil C₃₋₆ sustituido-Q², -alquil C₁₋₆-Q², -alquil C₁₋₆-sustituido con alquilo-Q², -cicloalquil C₃₋₆-Q², aril-Q², -NR¹³R¹⁴, y -OR¹⁵; en la que Q² se selecciona del grupo de arilo, heteroarilo, heteroarilo sustituido, -OR², -COOR², -NR⁸R⁹, SO₂R⁷, -CONHSO₂R³ y -CONHSO₂NR²R²; R⁷ se selecciona del grupo de -H, -alquilo C₁₋₆, -alquilo C₁₋₆ sustituido, -cicloalquilo C₃₋₆, -CF₃, arilo y heteroarilo; R⁸ y R⁹ se seleccionan independientemente entre el grupo de -H, -alquilo C₁₋₆, -alquilo C₁₋₆ sustituido, arilo, heteroarilo, arilo sustituido, heteroarilo sustituido, -alquil C₁₋₆-Q² y -COOR³, o R⁸ y R⁹ se toman junto con el N adyacente para formar un ciclo seleccionado del grupo de fórmulas (4); M se selecciona del grupo de -R¹⁵, -SO₂R², -SO₂NR²R², -OH y -NR²R¹²; V se selecciona del grupo de -CR¹⁰R¹¹-, -SO₂-, -O- y -NR¹²-; con la condición de que únicamente uno de R⁸ o R⁹ pueda ser -COOR³; R¹⁰ y R¹¹ se seleccionan independientemente entre el grupo de -H, -alquilo C₁₋₆, -alquilo C₁₋₆ sustituido y -cicloalquilo C₃₋₆; R¹² se selecciona del grupo de -H, -alquilo C₁₋₆, -alquilo C₁₋₆ sustituido con alquilo, -CONR²R², -SO₂R³ y -SO₂NR²R²; R¹³ y R¹⁴ se seleccionan independientemente entre el grupo de -H, -alquilo C₁₋₆, -cicloalquilo C₃₋₆, -alquilo C₁₋₆ sustituido, -alquil C₁₋₆-Q³, -alquil C₁₋₆-cicloalquil C₃₋₆-Q³ y alquil C₁₋₆ sustituido-Q³; Q³ se selecciona del grupo de heteroarilo, heteroarilo sustituido, -NR²R¹², -CONR²R², -COOR², -OR² y -SO₂R³; R¹⁵ se selecciona del grupo de -alquilo C₁₋₆, -cicloalquilo C₃₋₆, -alquilo C₁₋₆ sustituido, -alquil C₁₋₆-Q³, -alquil C₁₋₆-cicloalquil C₃₋₆-Q³ y -alquil C₁₋₆ sustituido-Q³; R¹⁶ se selecciona del grupo de -H, -alquilo C₁₋₆, -NR²R², y -COOR²; con la condición de que cuando V es -NR¹²-, R¹⁶ no sea -NR²R²; y R¹⁷ se selecciona del grupo de -H, -alquilo C₁₋₆, -COOR³ y arilo.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662291298P | 2016-02-04 | 2016-02-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
AR107512A1 true AR107512A1 (es) | 2018-05-09 |
Family
ID=57995251
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP170100255A AR107512A1 (es) | 2016-02-04 | 2017-02-01 | Triterpenoides modificados en c-3 y c-17 como inhibidores del vih-1 |
Country Status (38)
Country | Link |
---|---|
US (4) | US10421774B2 (es) |
EP (2) | EP3411381B1 (es) |
JP (1) | JP6735837B2 (es) |
KR (1) | KR20180105229A (es) |
CN (1) | CN109153700B (es) |
AR (1) | AR107512A1 (es) |
AU (1) | AU2017215529B2 (es) |
BR (1) | BR112018015629B1 (es) |
CA (1) | CA3013417C (es) |
CL (1) | CL2018002084A1 (es) |
CO (1) | CO2018008157A2 (es) |
CR (1) | CR20180387A (es) |
CY (1) | CY1124353T1 (es) |
DK (1) | DK3411381T3 (es) |
DO (1) | DOP2018000174A (es) |
EA (1) | EA036211B1 (es) |
ES (2) | ES2957767T3 (es) |
HK (1) | HK1256866A1 (es) |
HR (1) | HRP20210502T1 (es) |
HU (1) | HUE054337T2 (es) |
IL (1) | IL260741B (es) |
JO (1) | JOP20170029B1 (es) |
LT (1) | LT3411381T (es) |
MA (2) | MA53358A (es) |
MD (1) | MD3411381T2 (es) |
MX (1) | MX2018009514A (es) |
PE (1) | PE20181355A1 (es) |
PL (1) | PL3411381T3 (es) |
PT (1) | PT3411381T (es) |
RS (1) | RS61746B1 (es) |
RU (1) | RU2716502C2 (es) |
SG (1) | SG11201806388XA (es) |
SI (1) | SI3411381T1 (es) |
TW (1) | TWI719126B (es) |
UA (1) | UA123867C2 (es) |
UY (1) | UY37109A (es) |
WO (1) | WO2017134596A1 (es) |
ZA (1) | ZA201805044B (es) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR107512A1 (es) * | 2016-02-04 | 2018-05-09 | VIIV HEALTHCARE UK Nº 5 LTD | Triterpenoides modificados en c-3 y c-17 como inhibidores del vih-1 |
EP3784349B1 (en) | 2018-04-24 | 2023-12-27 | VIIV Healthcare UK (No.5) Limited | Compounds with hiv maturation inhibitory activity |
IL293566A (en) | 2019-12-09 | 2022-08-01 | Viiv Healthcare Co | Pharmaceutical preparations containing Cabotgravir |
WO2024089216A1 (en) | 2022-10-27 | 2024-05-02 | Syngenta Crop Protection Ag | Novel sulfur-containing heteroaryl carboxamide compounds |
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US5679828A (en) | 1995-06-05 | 1997-10-21 | Biotech Research Labs, Inc. | Betulinic acid and dihydrobetulinic acid derivatives and uses therefor |
US20040110785A1 (en) | 2001-02-02 | 2004-06-10 | Tao Wang | Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives |
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GB0301227D0 (en) | 2003-01-20 | 2003-02-19 | Keen Group Ltd | Seating apparatus |
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EP1730163A4 (en) | 2004-03-17 | 2009-12-30 | Panacos Pharmaceuticals Inc | Pharmaceutical salts of 3-O- (3,3-dimethylsuccinyl) betulinic acid |
TW200628161A (en) | 2004-11-12 | 2006-08-16 | Panacos Pharmaceuticals Inc | Novel betulin derivatives, preparation thereof and use thereof |
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CA2714049A1 (en) | 2008-02-14 | 2009-08-20 | Virochem Pharma Inc. | Novel 17.beta. lupane derivatives |
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DK2576586T3 (en) | 2010-06-04 | 2015-11-23 | Bristol Myers Squibb Co | C-28 AMINES OF MODIFIED C-3-BETULIN ACID DERIVATIVES AS ANTI-HUMIDITY INHIBITORS |
CN103038245B (zh) | 2010-06-04 | 2015-03-25 | 百时美施贵宝公司 | 作为hiv成熟抑制剂的c-3经修饰的桦木酸衍生物 |
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MY162186A (en) | 2011-01-31 | 2017-05-31 | Viiv Healthcare Uk (No 4) Ltd | C-17 and c-3 modified triterpenoids with hiv maturation inhibitory activity |
EP2670764B1 (en) | 2011-01-31 | 2015-09-02 | Bristol-Myers Squibb Company | C-28 amines of c-3 modified betulinic acid derivatives as hiv maturation inhibitors |
WO2013090683A1 (en) * | 2011-12-14 | 2013-06-20 | Glaxosmithkline Llc | Propenoate derivatives of betulin |
US8906889B2 (en) * | 2012-02-15 | 2014-12-09 | Bristol-Myers Squibb Company | C-3 cycloalkenyl triterpenoids with HIV maturation inhibitory activity |
US8889854B2 (en) | 2012-05-07 | 2014-11-18 | Bristol-Myers Squibb Company | C-17 bicyclic amines of triterpenoids with HIV maturation inhibitory activity |
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BR112015018491A2 (pt) * | 2013-02-06 | 2017-07-18 | Bristol Myers Squibb Co | triterpenoides c-19-modificados com atividade inibidora de maturação de hiv |
AU2014218754B2 (en) * | 2013-02-25 | 2017-04-20 | VIIV Healthcare UK (No.5) Limited | C-3 alkyl and alkenyl modified betulinic acid derivatives useful in the treatment of HIV |
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AR107512A1 (es) * | 2016-02-04 | 2018-05-09 | VIIV HEALTHCARE UK Nº 5 LTD | Triterpenoides modificados en c-3 y c-17 como inhibidores del vih-1 |
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2017
- 2017-02-01 AR ARP170100255A patent/AR107512A1/es active IP Right Grant
- 2017-02-02 RU RU2018130181A patent/RU2716502C2/ru active
- 2017-02-02 JP JP2018540806A patent/JP6735837B2/ja active Active
- 2017-02-02 KR KR1020187025343A patent/KR20180105229A/ko not_active Application Discontinuation
- 2017-02-02 DK DK17704093.8T patent/DK3411381T3/da active
- 2017-02-02 PL PL17704093T patent/PL3411381T3/pl unknown
- 2017-02-02 CA CA3013417A patent/CA3013417C/en active Active
- 2017-02-02 MA MA053358A patent/MA53358A/fr unknown
- 2017-02-02 EP EP17704093.8A patent/EP3411381B1/en active Active
- 2017-02-02 WO PCT/IB2017/050568 patent/WO2017134596A1/en active Application Filing
- 2017-02-02 MX MX2018009514A patent/MX2018009514A/es active IP Right Grant
- 2017-02-02 SG SG11201806388XA patent/SG11201806388XA/en unknown
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