AR105656A1 - Tratamiento de combinación que comprende la administración de 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas - Google Patents

Tratamiento de combinación que comprende la administración de 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas

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Publication number
AR105656A1
AR105656A1 ARP160102441A ARP160102441A AR105656A1 AR 105656 A1 AR105656 A1 AR 105656A1 AR P160102441 A ARP160102441 A AR P160102441A AR P160102441 A ARP160102441 A AR P160102441A AR 105656 A1 AR105656 A1 AR 105656A1
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Argentina
Prior art keywords
trifluoro
amino
dimethyl
tetrahydropyridin
fluorophenyl
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ARP160102441A
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English (en)
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H Lundbeck As
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
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    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4433Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • AHUMAN NECESSITIES
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • AHUMAN NECESSITIES
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/4965Non-condensed pyrazines
    • A61K31/497Non-condensed pyrazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
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    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
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    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Health & Medical Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
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  • Organic Chemistry (AREA)
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  • Psychiatry (AREA)
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  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

Composición farmacéutica, uso y compuestos. Reivindicación 1: Un método para el tratamiento de un trastorno neurodegenerativo o cognitivo, tal como enfermedad de Alzheimer, comprendiendo el método la administración, tal como la administración combinada, a un paciente que lo necesita, de una cantidad terapéuticamente efectiva de 1) un inhibidor de BACE1 de fórmula (1) en donde Ar se selecciona del grupo que consiste en fenilo, piridilo, pirimidilo, pirazinilo, imidazolilo, pirazolilo, 1,2,4-triazolilo, tiofenilo, tiazolilo, oxazolilo, isoxazolilo, 1,3,4-tiadiazolilo, isotiazolilo, 1,3,4-oxadiazolilo, 1,2,4-oxadiazolilo, furazanilo y 1,2,4-tiadiazolilo y en donde el Ar está opcionalmente sustituido con uno o más de entre halógeno, CN, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, fluoroalquilo C₁₋₆ o alcoxi C₁₋₆; R¹ es alquilo C₁₋₃ o fluoroalquilo C₁₋₃; R² es hidrógeno, halógeno, fluoroalquilo C₁₋₃ o alquilo C₁₋₃; R³ es alquilo C₁₋₃; o una sal farmacéuticamente aceptable del mismo; y 2) un compuesto útil en la inmunoterapia de Tau activa o pasiva, un compuesto útil en la inmunoterapia de péptido Ab activa o pasiva, un antagonista de receptor de NMDA, un inhibidor de acetilcolina esterasa, un antiepiléptico, un fármaco antiinflamatorio, un inhibidor de la agregación de proteína Tau o un SSRI. Reivindicación 2: El método de acuerdo con la reivindicación 1, en donde dicho inhibidor de BACE1 se selecciona del grupo que consiste en N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-fluoropicolinamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-fluoropicolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-cloropicolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-cianopicolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-metoxipirazina-2-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-1-(difluorometil)-1H-pirazol-3-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-2-metiloxazol-4-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)tiazol-2-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-bromo-1-metil-1H-imidazol-2-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-metiltiazol-2-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-(trifluorometil)-picolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-metoxipirimidina-2-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-2-difluorometil)oxazol-4-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-fluorometil)oxazol-2-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-fluorometil)tiazol-2-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-(difluorometil)pirazina-2-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-metoxipicolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-ciano-3-metilpicolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-3-metil-1,2,4-oxadiazol-5-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-1-metil-1H-1,2,4-triazol-3-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-1-(difluorometil)-1H-pirazol-3-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-(difluorometil)pirazina-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-metoxipirazina-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-metoxipirimidina-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-metiltiazol-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-(trifluorometil)picolinamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-2-difluorometil)oxazol-4-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-fluorometil)oxazol-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-fluorometil)tiazol-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-cianopicolinamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-cloropicolinamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-2-metiloxazol-4-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-metil-1,2,4-oxadiazol-3-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)tiazol-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-bromo-1-metil-1H-imidazol-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-1,4-dimetil-1H-imidazol-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-3-metilisoxazol-5-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-metilfuran-2-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-2-metiloxazol-5-carboxamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-(metoxi-d₃)picolinamida; N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-4-clorobenzamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-(difluorometoxi)picolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-3-fluoro-5-metoxipicolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-2,5-dimetiloxazol-4-carboxamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-5-(metoxi-d₃)picolinamida; N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimetil-2,3,4,5-tetrahidropiridin-2-il)-4-fluorofenil)-5-fluoro-3-metilpicolinamida; o una sal farmacéuticamente aceptable del mismo.
ARP160102441A 2015-08-10 2016-08-09 Tratamiento de combinación que comprende la administración de 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahidropiridinas AR105656A1 (es)

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DKPA201500456 2015-08-10
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PE20180696A1 (es) 2018-04-23
CN107921138A (zh) 2018-04-17
PH12018500300A1 (en) 2018-08-29
US10004738B2 (en) 2018-06-26
AU2016305260A1 (en) 2018-02-15
TN2018000041A1 (en) 2019-07-08
ECSP18010534A (es) 2018-04-30
MA42611A (fr) 2018-06-20
MX2018001636A (es) 2018-05-07
CA2993623A1 (en) 2017-02-16
US20170042895A1 (en) 2017-02-16
EA201890257A1 (ru) 2018-07-31
RU2018104867A (ru) 2019-09-12
DOP2018000039A (es) 2018-04-30
CL2018000339A1 (es) 2018-07-06
EP3334461A1 (en) 2018-06-20
SV2018005628A (es) 2018-04-19
CO2018000711A2 (es) 2018-05-10
IL257072A (en) 2018-03-29
JP2018529647A (ja) 2018-10-11
TW201717948A (zh) 2017-06-01
BR112017007306A2 (pt) 2018-03-27

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