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AR115993A2 - Composiciones de pirrolopirrol como activadores de piruvato quinasa (pkr) - Google Patents

Composiciones de pirrolopirrol como activadores de piruvato quinasa (pkr)

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Publication number
AR115993A2
AR115993A2 ARP190102376A ARP190102376A AR115993A2 AR 115993 A2 AR115993 A2 AR 115993A2 AR P190102376 A ARP190102376 A AR P190102376A AR P190102376 A ARP190102376 A AR P190102376A AR 115993 A2 AR115993 A2 AR 115993A2
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Argentina
Prior art keywords
cycloalkyl
optionally substituted
atoms
cycloalkenyl
alkynyl
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ARP190102376A
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English (en)
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Forma Therapeutics Inc
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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
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • 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
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicinal Preparation (AREA)
  • Pyridine Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La divulgación se refiere a la modulación de piruvato quinasa y proporciona compuestos químicos como activadores ele PKR, así como a los diversos usos de estos compuestos. Compuestos activadores de PKR útiles en el tratamiento de enfermedades y trastornos asociados con PKR y/o PKM2. Reivindicación 1: Un compuesto de fórmula (1), o una sal farmacéuticamente aceptable de este, donde: Y es un enlace, -(CR⁵R⁵’)ₜ-, -NR⁵(CR⁵R⁵’)ₜ- u -O-; cada R¹, R¹’, R² y R²’ es independientemente -H, alquilo C₁₋₆, -alquenilo C₂₋₆, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, -cicloalquenilo C₄₋₈, heterociclilo, arilo, heteroarilo, halógeno, -CN, -OR⁵, -SR⁵, -NO₂, -NR⁵R⁵’, -S(O)₂R⁵, -S(O)₂NR⁵R⁵’, -S(O)R⁵, -S(O)NR⁵R⁵’, -NR⁵S(O)₂R⁵’, -NR⁵S(O)R⁵’, -C(O)R⁵ o -C(O)OR⁵, donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, heterociclilo, arilo o heteroarilo se sustituye opcionalmente con uno o más sustituyentes que se seleccionan del grupo que consiste en oxo, halógeno, -CN, -R⁵, -OR⁵, -SR⁵, -NO₂, -NR⁵R⁵’, -S(O)₂R⁵, -S(O)₂NR⁵R⁵’, -S(O)R⁵, -S(O)NR⁵R⁵’, -NR⁵S(O)₂R⁵’, -NR⁵S(O)R⁵’, -C(O)R⁵ y C(O)OR⁵; o R¹ y R¹’, o R² y R²’, junto con el átomo al que se acoplan, pueden combinarse para formar un anillo -cicloalquilo C₃₋₈, heterociclo, espirociclo C₅₋₈ o espiroheterociclo de 5 a 8 miembros; o R¹ y R², junto con los átomos a los cuales se acoplan, pueden combinarse para formar un -cicloalquilo C₃₋₈ o un heterociclo de 3 a 8 miembros; R³ es independientemente -H, -alquilo C₁₋₆, -alquenilo C₂₋₆, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, -cicloalquenilo C₄₋₈, heterociclilo, arilo, heteroarilo, -S(O)₂R⁵, -S(O)₂NR⁵R⁵’, -S(O)R⁵, -S(O)NR⁵R⁵’, -C(O)R⁵ o -C(O)OR⁵, donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, heterociclilo, arilo o heteroarilo se sustituye opcionalmente con uno o más sustituyentes que se seleccionan del grupo que consiste en oxo, halógeno, -CN, -R⁵, -OR⁵, -SR⁵, -NO₂, -NR⁵R⁵’, -S(O)₂R⁵, -S(O)₂NR⁵R⁵’, -S(O)R⁵, -S(O)NR⁵R⁵’, -NR⁵S(O)₂R⁵’, -NR⁵S(O)R⁵’, -C(O)R⁵ y -C(O)OR⁵; o R² y R³, junto con los átomos a los que se unen, pueden combinarse para formar un anillo heterocíclico de 5 a 8 miembros; o R¹ y R³, junto con los átomos a los que se unen, pueden combinarse para formar un anillo heterocíclico de 5 a 8 miembros; R⁴ es -H, -alquilo C₁₋₆, -alquenilo C₂₋₆, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, cicloalquenilo C₄₋₈, heterociclilo, arilo, heteroarilo, halógeno, -CN, -OR⁵, -SR⁵, -NO₂, -NR⁵R⁵’, -S(O)₂R⁵, -S(O)₂NR⁵R⁵’, -S(O)R⁵, -S(O)NR⁵R⁵’, -NR⁵S(O)₂R⁵’, -NR⁵S(O)R⁵’, -C(O)R⁵ o -C(O)OR⁵, donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, heterociclilo, arilo o heteroarilo se sustituye opcionalmente con uno o más sustituyentes que se seleccionan del grupo que consiste en oxo, halógeno, -CN, -R⁵, -OR⁵, -SR⁵, -NO₂, -NR⁵R⁵’, -S(O)₂R⁵, -S(O)₂NR⁵R⁵’, -S(O)R⁵, -S(O)NR⁵R⁵’, -NR⁵S(O)₂R⁵’, -NR⁵S(O)R⁵’, -C(O)R⁵ y -CO(O)R⁵; en cada aparición, cada R⁵ y R⁵’ es independientemente -H, -alquilo C₁₋₆, -alquenilo C₂₋₆, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, cicloalquenilo C₄₋₈, heterociclilo, arilo, heteroarilo, halógeno, -CN, -OR⁶, -SR⁶, -NO₂, -NR⁶R⁶’, -S(O)₂R⁶, -S(O)₂NR⁶R⁶’, -S(O)R⁶, -S(O)NR⁶R⁶’, -NR⁶S(O)₂R⁶’, -NR⁶S(O)R⁶’, -C(O)R⁶ o -C(O)OR⁶, donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, heterociclilo, arilo o heteroarilo se sustituye opcionalmente con uno o más sustituyentes que se seleccionan del grupo que consiste en oxo, halógeno, -CN, -R⁶, -OR⁶, -SR⁶, -NO₂, -NR⁶R⁶’, -S(O)₂R⁶, -S(O)₂NR⁶R⁶’, -S(O)R⁶, -S(O)NR⁶R⁶’, -NR⁶S(O)₂R⁶’, -NR⁶S(O)R⁶’, -C(O)R⁶ y -C(O)OR⁶; o dos R⁵ en átomos adyacentes, junto con los átomos a los que se acoplan, forman un anillo arilo sustituido opcionalmente con uno o más R⁶; o dos R⁵en átomos adyacentes, junto con los átomos a los que se acoplan, forman un anillo heteroarilo sustituido opcionalmente con uno o más R⁶; o dos R⁵ en átomos adyacentes, junto con los átomos a los que se acoplan, forman un anillo cicloalquilo C₃₋₈ sustituido opcionalmente con uno o más R⁶; o dos R⁵ en átomos adyacentes, junto con los átomos a los que se acoplan, forman un anillo heterocicloalquilo sustituido opcionalmente con uno o más R⁶; o dos R⁵’ en átomos adyacentes, junto con los átomos a los que se acoplan, forman un anillo arilo sustituido opcionalmente con uno o más R⁶; o dos R⁵’ en átomos adyacentes, junto con los átomos a los que se acoplan, forman un anillo heteroarilo sustituido opcionalmente con uno o más R⁶; o dos R⁵’ en átomos adyacentes, junto con los átomos a los que se acoplan, forman un anillo cicloalquilo C₃₋₈ sustituido opcionalmente con uno o más R⁶; o dos R⁵’ en átomos adyacentes, junto con los átomos a los que se acoplan, forman un anillo heterocicloalquilo sustituido opcionalmente con una o más R⁶; en cada aparición, cada R⁶ y R⁶’ es independientemente -H, -alquilo C₁₋₆, -alquenilo C₂₋₆, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈, -cicloalquenilo C₄₋₈, heterociclilo, arilo, heteroarilo, halógeno, -CN, -OR⁷, -SR⁷, -NO₂, -NR⁷R⁷’, -S(O)₂R⁷, -S(O)₂NR⁷R⁷’, -S(O)R⁷, -S(O)NR⁷R⁷’, -NR⁷S(O)₂R⁷’, -NR⁷S(O)R⁷’, -C(O)R⁷ o -C(O)OR⁷, donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, heterociclilo, arilo o heteroarilo se sustituye opcionalmente con uno o más sustituyentes que se seleccionan del grupo que consiste en oxo, halógeno, -CN, -R⁷, -OR⁷, -SR⁷, -NO₂, -NR⁷R⁷’, -S(O)₂R⁷, -S(O)₂NR⁷R⁷’, -S(O)R⁷, -S(O)NR⁷R⁷’, -NR⁷S(O)₂R⁷’, -NR⁷S(O)R⁷’, -C(O)R⁷ y -C(O)OR⁷; en cada aparición, cada R⁷ y R⁷’ es independientemente H, -alquilo C₁₋₆, -alquenilo C₂₋₆, -alquinilo C₂₋₆, cicloalquilo C₃₋₈, -cicloalquenilo C₄₋₈, heterociclilo, arilo, heteroarilo, halógeno, -CN, -OH, -SH, -NO₂, -NH₂, -S(O)₂H, -S(O)₂NH₂, -S(O)H, -S(O)NH₂, -NHS(O)₂H, -NHS(O)H, -C(O)H o -C(O)OH, donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, heterociclilo, arilo o heterociclilo se sustituye opcionalmente con uno o más sustituyentes que se seleccionan del grupo que consiste en oxo, halógeno, -CN, -OH, -SH, -NO₂, -NH₂, -S(O)₂H, -S(O)₂NH₂, -S(O)H, -S(O)NH₂, -NHS(O)₂H, -NHS(O)H, -C(O)H y -C(O)OH; en cada aparición, cada R⁸, R⁸’, R⁹, R⁹’, R¹⁰, R¹⁰’, R¹¹ y R¹¹’ es independientemente -H, -alquilo C₁₋₆, -alquenilo C₂₋₆, -alquinilo C₂₋₆, -cicloalquilo C₃₋₈ o -cicloalquenilo C₄₋₈, donde cada alquilo, alquenilo, alquinilo, cicloalquilo y cicloalquenilo se sustituye opcionalmente con uno o más sustituyentes que se seleccionan del grupo que consiste en oxo, halógeno, -CN, -R⁷, -OR⁷, -SR⁷, -NO₂, -NR⁷R⁷’, -S(O)₂R⁷, -S(O)₂NR⁷R⁷’, -S(O)R⁷, -S(O)NR⁷R⁷’, -NR⁷S(O)₂R⁷’, -NR⁷S(O)R⁷’, -C(O)R⁷ y -C(O)OR⁷; y t es 0, 1, 2 ó 3.
ARP190102376A 2017-03-20 2019-08-21 Composiciones de pirrolopirrol como activadores de piruvato quinasa (pkr) AR115993A2 (es)

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AU (4) AU2018240172C1 (es)
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