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AR096052A1 - Compuestos y sus usos para la modulación de hemoglobina - Google Patents

Compuestos y sus usos para la modulación de hemoglobina

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Publication number
AR096052A1
AR096052A1 ARP140101658A ARP140101658A AR096052A1 AR 096052 A1 AR096052 A1 AR 096052A1 AR P140101658 A ARP140101658 A AR P140101658A AR P140101658 A ARP140101658 A AR P140101658A AR 096052 A1 AR096052 A1 AR 096052A1
Authority
AR
Argentina
Prior art keywords
optionally substituted
ring
alkyl
aryl
heteroatoms
Prior art date
Application number
ARP140101658A
Other languages
English (en)
Inventor
Li Zhe
W Metcalf Brian
L Gwaltney Stephen
W Yee Calvin
Xu Qing
R Harris Jason
Original Assignee
Global Blood Therapeutics 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
Application filed by Global Blood Therapeutics Inc filed Critical Global Blood Therapeutics Inc
Publication of AR096052A1 publication Critical patent/AR096052A1/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Se brindan compuestos y composiciones farmacéuticas convenientes como moduladores de la hemoglobina, métodos e intermediarios para su preparación, y métodos para usarlos en el tratamiento de trastornos mediados por la hemoglobina y trastornos que podrían mejorar por la oxigenación tisular y/o celular. Reivindicación 1: Un compuesto de fórmula (1) o uno de sus tautómeros o una sal farmacéuticamente aceptable de cada uno de ellos, donde L¹⁰ es metileno opcionalmente sustituido o, preferentemente, un enlace; el anillo A es un arilo C₆₋₁₀, un cicloalquilo C₃₋₈, un heteroarilo de 5 - 10 miembros o un heterociclo de 4 - 10 miembros que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, donde cada arilo, heteroarilo, cicloalquilo o heterociclo está opcionalmente sustituido, preferentemente, por 1 - 4: halo, alquilo C₁₋₆, alcoxi C₁₋₆, y/o cicloalquilo C₃₋₁₀, donde el alquilo C₁₋₆ está opcionalmente sustituido por 1 - 5 halo, alcoxi C₁₋₆ y/o cicloalquilo C₃₋₁₀; o el anillo A es arilo C₆₋₁₀, o un heteroarilo de 5 - 10 miembros, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, donde cada arilo o heteroarilo está opcionalmente sustituido, preferentemente, por 1 - 4 grupos alquilo C₁₋₆ y/o alcoxi C₁₋₆; el anillo B es un heteroarilo de 5 - 10 miembros o un heterociclo de 4 - 10 miembros que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, donde cada uno de los heteroarilo y heterociclo está opcionalmente sustituido, preferentemente, por 1 - 4: halo, alquilo C₁₋₆ y/o -CO-alquilo C₁₋₆, el anillo B es de fórmula (2) ó (3), en la cual el anillo B incluye la parte -N-CO- es un heterociclo de 5 - 6 miembros que comprende hasta 3 heteroátomos seleccionados entre nitrógeno, oxígeno y azufre y formas oxidadas de N y S, donde cada uno de los heteroarilo y heterociclo está opcionalmente sustituido, preferentemente, por 1 - 4 grupos alquilo C₁₋₆; ⁻ ⁻ ⁻ ⁻ ⁻ es un enlace simple o un enlace doble; cada X e Y es, independientemente, CR²⁰R²¹, O, S, SO, SO₂, o NR²⁰; e es 1 a 4, preferentemente, 1; cada R²⁰ y R²¹ es, independientemente, hidrógeno o alquilo C₁₋₃ opcionalmente sustituido por 1 - 3 halo, OH, o alcoxi C₁₋₆ o CR²⁰R²¹ es C=O, siempre y cuando, si uno de X e Y es O, S, SO, SO₂, entonces el otro no es CO, y X e Y ambos no son heteroátomos o formas oxidadas de ellos; el anillo C es arilo C₆₋₁₀ o un heteroarilo de 5 - 10 miembros que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, cada uno de los cuales está opcionalmente sustituido, preferentemente, por 1 - 4: halo, oxo, -OR¹, alquilo C₁₋₆, -COOR¹, y/o alcoxi C₁₋₆, donde el alquilo C₁₋₆ está opcionalmente sustituido por 1 - 5 halo, alcoxi C₁₋₆ y/o un heterociclo de 4 - 10 miembros que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S; o el anillo C es arilo C₆₋₁₀ o un heteroarilo de 5 - 10 miembros que contiene hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, cada uno de los cuales está opcionalmente sustituido, preferentemente, por 1 - 4: halo, oxo, -OR¹, alquilo C₁₋₆, COOR¹, y NR⁵R⁶; R¹ es un hidrógeno, alquilo C₁₋₆ o una parte del profármaco; donde el alquilo está opcionalmente sustituido por un heteroarilo de 5 - 10 miembros que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, que está opcionalmente sustituido por un heteroarilo de 5 - 10 miembros que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, donde el heteroarilo está opcionalmente sustituido por alquilo C₁₋₆; R⁵ y R⁶ son cada uno, independientemente, hidrógeno, alquilo C₁₋₆ opcionalmente sustituido, o -COOR³; R³ es hidrógeno o alquilo C₁₋₆ opcionalmente sustituido; siempre que cuando el anillo C es arilo C₁₋₆; V¹ y V² son, independientemente, alcoxi C₁₋₆; o V¹ y V² junto con el átomo de carbono al que están unidos forman un anillo de fórmula (4) en la cual cada V³ y V⁴ son, independientemente, O, S, o NH, siempre que cuando uno de V³ y V⁴ es S, el otro sea NH, y siempre que V³ y V⁴ ambos no sean NH; q es 1 ó 2; cada V⁵ es, independientemente, alquilo C₁₋₆ opcionalmente sustituido por 1 - 3 grupos OH, o V⁵ es CO₂R⁶⁰ donde cada R⁶⁰ es, independientemente, alquilo C₁₋₆ o hidrógeno; t es 0, 1, 2, ó 4; o CV¹V² es C=V, donde V es O, NOR⁸⁰, o NNR⁸¹R⁸²; R⁸⁰ es alquilo C₁₋₆ opcionalmente sustituido; R⁸¹ y R⁸² se seleccionan, independientemente, entre el grupo que comprende hidrógeno, alquilo C₁₋₆ opcionalmente sustituido, COR⁸³ o CO₂R⁸⁴; R⁸³ es hidrógeno o alquilo C₁₋₆ opcionalmente sustituido; y R⁸⁴ es alquilo C₁₋₆ opcionalmente sustituido; siempre que cuando el anillo C es arilo C₁₋₆; y el anillo B es heterociclilo de 4 - 10 miembros opcionalmente sustituido; entonces el anillo A excluye heteroarilo de 5 - 10 miembros opcionalmente sustituido; y siempre que cuando el anillo C es arilo C₆₋₁₀; y el anillo B es heteroarilo de 5 - 10 miembros opcionalmente sustituido; entonces el anillo A no es heterociclo de 4 - 10 miembros opcionalmente sustituido.
ARP140101658A 2013-11-18 2014-04-22 Compuestos y sus usos para la modulación de hemoglobina AR096052A1 (es)

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