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
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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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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/4353—Heterocyclic 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
    • A61K31/436—Heterocyclic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic 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
    • A61K31/407—Heterocyclic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic 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)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (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)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (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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EP (3) EP3448859B1 (es)
JP (2) JP6594570B2 (es)
KR (2) KR102007135B1 (es)
CN (2) CN109311897B (es)
AR (2) AR111295A1 (es)
AU (4) AU2018240172C1 (es)
CA (1) CA3024181C (es)
CY (2) CY1122393T1 (es)
DK (2) DK3448859T3 (es)
EA (1) EA201992215A1 (es)
ES (2) ES2747768T3 (es)
HR (2) HRP20191665T1 (es)
HU (2) HUE049979T2 (es)
IL (2) IL269447B (es)
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NZ (2) NZ748072A (es)
PL (2) PL3448859T3 (es)
PT (2) PT3448859T (es)
RS (2) RS59306B1 (es)
RU (3) RU2736217C2 (es)
SA (1) SA519410164B1 (es)
SG (1) SG11201908670SA (es)
SI (2) SI3483164T1 (es)
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