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AR102467A1 - Métodos para tratar infecciones por el virus filoviridae - Google Patents

Métodos para tratar infecciones por el virus filoviridae

Info

Publication number
AR102467A1
AR102467A1 ARP150103505A ARP150103505A AR102467A1 AR 102467 A1 AR102467 A1 AR 102467A1 AR P150103505 A ARP150103505 A AR P150103505A AR P150103505 A ARP150103505 A AR P150103505A AR 102467 A1 AR102467 A1 AR 102467A1
Authority
AR
Argentina
Prior art keywords
group
alkyl
independently
substituted
formula
Prior art date
Application number
ARP150103505A
Other languages
English (en)
Inventor
Siegel Dustin
S Ray Adrian
P Parrish Jay
L Mackman Richard
Jordan Robert
Chung Hui Hon
Doerffler Edward
Oneil Hanrahan Clarke Michael
Kwon Chun Byoung
Original Assignee
Gilead Sciences Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=54557474&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR102467(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of AR102467A1 publication Critical patent/AR102467A1/es

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    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
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  • Communicable Diseases (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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  • Plural Heterocyclic Compounds (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Se proporcionan compuestos, métodos, y composiciones farmacéuticas para tratar infecciones por el virus Filoviridae administrando ribósidos, fosfatos de ribósido, y profármacos del mismo. Los compuestos, composiciones, y métodos provistos son particularmente útiles para el tratamiento de infecciones por el virus de Marburg, virus de Ebola y virus Cueva. Reivindicación 1: Un método para tratar una infección por Filoviridae en un humano que necesita del mismo que comprende administrar una cantidad terapéuticamente efectiva de un compuesto de fórmula (1) o una sal, hidrato o éster farmacéuticamente estable, del mismo; en donde, R⁷ se selecciona del grupo que consiste en a) H, -C(=O)R¹¹, -C(=O)OR¹¹, -C(=O)NR¹¹R¹², -C(=O)SR¹¹, -S(O)R¹¹, -S(O)₂R¹¹, -S(O)(OR¹¹), -S(O)₂(OR¹¹), o -SO₂NR¹¹R¹², b) un resto del grupo de fórmulas (2), c) un resto del grupo de fórmulas (3), en donde: Rᶜ se selecciona del grupo de fenilo, 1-naftilo, 2-naftilo, un resto de fórmula (4) y un resto de fórmula (5); Rᵈ se selecciona del grupo de H o CH₃; Rᵉ¹ y Rᵉ² se seleccionan cada uno independientemente del grupo de H, alquilo C₁₋₆ o bencilo; Rᶠ se selecciona del grupo de H, alquilo C₁₋₈, bencilo, cicloalquilo C₃₋₆, y -CH₂-cicloalquilo C₃₋₆; Rᵍ se selecciona del grupo de alquilo C₁₋₈, -O-alquilo C₁₋₈, bencilo, -O-bencilo, -CH₂-cicloalquilo C₃₋₆, -O-CH₂-cicloalquilo C₃₋₆, y CF₃; y n es un entero seleccionado del grupo de 1, 2, 3, y 4; y d) un grupo de fórmula (6), en donde Q se selecciona del grupo de O, S, NR, ⁺N(O)(R), N(O), ⁺N(O)(O), o N-NR₂; Z¹ y Z², cuando se toman juntos, son -Q¹(C(Rʸ)₂)₃Q¹- en donde cada Q¹ se selecciona independientemente del grupo de O, S, o NR; y cada Rʸ se selecciona independientemente del grupo de H, F, Cl, Br, I, OH, R, -C(=Q²)R, -C(=Q²)O, -C(=Q²)N(R)₂, -N(R)₂, -⁺N(R)₃, -SR, -S(O)R, -S(O)₂R, -S(O)(O), -S(O)₂(O), -OC(=Q¹)R, -OC(=Q²)O, -OC(=Q²)(N(R)₂), -SC(=Q²)R, -SC(=Q²)O, -SC(=Q²)(N(R)₂), -N(R)C(=Q²)R, -N(R)C(=Q²)O, -N(R)C(=Q²)N(R)₂, -SO₂NR₂, -CN, -N₃, -NO₂, -O, o Z³; o cuando se toman juntos, dos Rʸ sobre el mismo átomo de carbono forman un anillo carbocíclico de 3 a 7 átomos de carbono; cada Q² es independientemente, O, S, NR, ⁺N(O)(R), N(O), ⁺N(O)(O), o N-NR₂; o Z¹ y Z² son cada, independientemente, un grupo de fórmula (7) en donde: cada Q³ se selecciona independientemente del grupo de un enlace, O, CR₂, NR, ⁺N(O)(R), N(O), ⁺N(O)(O), N-NR₂, S, S-S, S(O), o S(O)₂; M2 es un entero seleccionado del grupo de 0, 1 ó 2; cada Rˣ es independientemente Rʸ o la fórmula (8) en donde: cada M1a, M1c, y M1d es un entero independientemente seleccionado del grupo de 0 ó 1; M12c es un entero seleccionado del grupo de 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 ó 12; Z³ es Z⁴ o Z⁵; Z⁴ es R, -C(Q²)Rʸ, -C(Q²)Z⁵, -SO₂Rʸ, o -SO₂Z⁵; y Z⁵ es un carbociclo o un heterociclo en donde Z⁵ está sustituido independientemente con 0 a 3 grupos Rʸ; cada R¹¹ o R¹² es independientemente H, alquilo C₁₋₈, alquenilo C₂₋₈, alquinilo C₂₋₈, carbociclilalquilo C₄₋₈, arilo C₆₋₂₀ opcionalmente sustituido, heteroarilo opcionalmente sustituido, -C(=O)alquilo C₁₋₈, -S(O)ₙ-alquilo C₁₋₈ o arilo C₆₋₂₀alquilo C₁₋₈; o R¹¹ y R¹² tomados juntos con un nitrógeno al que están ambos unidos forman un anillo heterocíclico de 3 a 7 miembros en donde cualquier átomo de carbono de dicho anillo heterocíclico se puede reemplazar opcionalmente con -O-, -S- o -NRᵃ-; cada Rᵃ se selecciona independientemente del grupo de H, alquilo C₁₋₈, alquenilo C₂₋₈, alquinilo C₂₋₈, arilo C₆₋₂₀ alquilo C₁₋₈, carbociclilalquilo C₄₋₈, -C(=O)R, -C(=O)O, -C(=O)NR₂, -C(=O)SR, -S(O)R, -S(O)₂R, -S(O)(O), -S(O)₂(O), o -SO₂NR₂; en donde cada R se selecciona independientemente del grupo de H, alquilo C₁₋₈, alquilo C₁₋₈ sustituido, alquenilo C₂₋₈, alquenilo C₂₋₈ sustituido, alquinilo C₂₋₈, alquinilo C₂₋₈ sustituido, arilo C₆₋₂₀, arilo C₆₋₂₀ sustituido, heterociclilo C₂₋₂₀ heterociclilo C₂₋₂₀ sustituido, arilo C₆₋₂₀alquilo C₁₋₈ o arilo C₆₋₂₀alquilo C₁₋₈ sustituido; cada n es un entero independientemente seleccionado del grupo de 0, 1, ó 2; y en donde cada alquilo C₁₋₈, alquenilo C₂₋₈, alquinilo C₂₋₈, arilo C₆₋₂₀alquilo C₁₋₈ de cada R¹¹ o R¹² está, independientemente, opcionalmente sustituido con uno o más sustituyentes seleccionados del grupo de halo, hidroxi, CN, N₃, N(Rᵃ)₂ o ORᵃ; y en donde uno o más de los átomos no terminales de carbono de cada dicho alquilo C₁₋₈ se pueden reemplazar opcionalmente con -O-, -S- o -NRᵃ-.
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