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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-1

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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
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AR
Argentina
Prior art keywords
alkyl
substituted
group
heteroaryl
cycloalkyl
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Application number
ARP170100255A
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English (en)
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VIIV HEALTHCARE UK Nº 5 LTD
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Publication of AR107512A1 publication Critical patent/AR107512A1/es

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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
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J53/00Steroids 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
    • C07J53/002Carbocyclic rings fused
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/18Antivirals for RNA viruses for HIV
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/06Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/06Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J63/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/008Expansion of ring D by one atom, e.g. D homo steroids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/503Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses
    • C12N9/506Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses derived from RNA viruses
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00Systems containing at least three condensed rings
    • C07C2603/02Ortho- or ortho- and peri-condensed systems
    • C07C2603/52Ortho- or ortho- and peri-condensed systems containing five condensed rings
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00Reverse transcribing RNA viruses
    • C12N2740/00011Details
    • C12N2740/10011Retroviridae
    • C12N2740/16011Human Immunodeficiency Virus, HIV
    • C12N2740/16211Human Immunodeficiency Virus, HIV concerning HIV gagpol
    • C12N2740/16222New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

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  • 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.
ARP170100255A 2016-02-04 2017-02-01 Triterpenoides modificados en c-3 y c-17 como inhibidores del vih-1 AR107512A1 (es)

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SG11201806388XA (en) 2018-08-30
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EA036211B1 (ru) 2020-10-14
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AU2017215529A8 (en) 2018-08-30
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JP2019504104A (ja) 2019-02-14
SI3411381T1 (sl) 2021-04-30
HRP20210502T1 (hr) 2021-05-14
PE20181355A1 (es) 2018-08-22
CO2018008157A2 (es) 2018-08-21
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HUE054337T2 (hu) 2021-08-30
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US20230295220A1 (en) 2023-09-21
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DOP2018000174A (es) 2018-10-31
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US20190359647A1 (en) 2019-11-28
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CN109153700B (zh) 2021-03-09
CR20180387A (es) 2018-09-20
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PT3411381T (pt) 2021-03-18
RS61746B1 (sr) 2021-05-31
UA123867C2 (uk) 2021-06-16
US10421774B2 (en) 2019-09-24
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US20210323997A1 (en) 2021-10-21
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