AR127500A1 - Inhibidores de la proteína que contiene el dominio de prolil hidroxilasa (phd) y usos de los mismos - Google Patents

Inhibidores de la proteína que contiene el dominio de prolil hidroxilasa (phd) y usos de los mismos

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AR127500A1
AR127500A1 ARP220102947A ARP220102947A AR127500A1 AR 127500 A1 AR127500 A1 AR 127500A1 AR P220102947 A ARP220102947 A AR P220102947A AR P220102947 A ARP220102947 A AR P220102947A AR 127500 A1 AR127500 A1 AR 127500A1
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alkyl
nrcrd
heterocycloalkyl
cycloalkyl
heteroalkyl
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Liena Qin
Xiao Ding
Feng Ren
Jianyu Xu
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Insilico Medicine Ip Ltd
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    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • 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
    • A61K31/4375Heterocyclic 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 nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P7/06Antianaemics
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    • 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
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom

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  • Chemical & Material Sciences (AREA)
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  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

En la presente se describen inhibidores de PHD y composiciones farmacéuticas que comprenden estos inhibidores. Los compuestos y composiciones de la presente son útiles para el tratamiento de la enfermedad intestinal inflamatoria. Reivindicación 1: Un compuesto de la fórmula (1), o una sal farmacéuticamente aceptable, o estereoisómero del mismo, en donde: R¹ es heterocicloalquilo monocíclico opcionalmente e independientemente sustituido con uno o más R¹ᵃ; cada R¹ᵃ es independientemente halógeno, -CN, -NO₂, -OH, -ORᵃ, -OC(=O)Rᵃ, -OC(=O)ORᵇ, -OC(=O)NRᶜRᵈ, -SH, -SRᵃ, -S(=O)Rᵃ, -S(=O)₂Rᵃ, -S(=O)₂NRᶜRᵈ, -NRᶜRᵈ, -NRᵇC(=O)NRᶜRᵈ, -NRᵇC(=O)Rᵃ, -NRᵇC(=O)ORᵇ, -NRᵇS(=O)₂Rᵃ, -C(=O)Rᵃ, -C(=O)ORᵇ, -C(=O)NRᶜRᵈ, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo, C₁-C₆ heteroalquilo, C₂-C₆ alquenilo, C₂-C₆ alquinilo, cicloalquilo, heterocicloalquilo, arilo o heteroarilo; o dos R¹ᵃ en el mismo átomo se toman conjuntamente para formar un oxo; X es N o CR²; R² es hidrógeno, fluoro, cloro, bromo, -CN, -NO₂, -OH, -ORᵃ, -C(=O)Rᵃ, -C(=O)ORᵇ, -C(=O)NRᶜRᵈ, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo o C₁-C₆ heteroalquilo; R³ es hidrógeno, halógeno, -CN, -NO₂, -OH, -ORᵃ, -C(=O)Rᵃ, -C(=O)ORᵇ, -C(=O)NRᶜRᵈ, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo o C₁-C₆ heteroalquilo; R⁴ es hidrógeno, halógeno, -CN, -NO₂, -OH, -ORᵃ, -C(=O)Rᵃ, -C(=O)ORᵇ, -C(=O)NRᶜRᵈ, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo o C₁-C₆ heteroalquilo; R⁵ es hidrógeno, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo o C₁-C₆ heteroalquilo; Y es -O-, -S- o -NR⁶-; R⁶ es hidrógeno, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo o C₁-C₆ heteroalquilo; L es -(CR⁷R⁸)ₚ-; cada R⁷ y R⁸ es independientemente hidrógeno, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo o C₁-C₆ heteroalquilo; o R⁷ y R⁸ en el mismo carbono se toman conjuntamente para formar un cicloalquilo o heterocicloalquilo; cada uno opcionalmente sustituido con uno o más R⁷ᵃ; cada R⁷ᵃ es independientemente halógeno, -CN, -NO₂, -OH, -ORᵃ, -NRᶜRᵈ, -C(=O)Rᵃ, -C(=O)ORᵇ, -C(=O)NRᶜRᵈ, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo o C₁-C₆ heteroalquilo; p es 0 - 4; El anillo A es cicloalquilo, heterocicloalquilo, arilo o heteroarilo; cada R⁹ es independientemente halógeno, -CN, -NO₂, -OH, -ORᵃ, -OC(=O)Rᵃ, -OC(=O)ORᵇ, -OC(=O)NRᶜRᵈ, -SH, -SRᵃ, -S(=O)Rᵃ, -S(=O)₂Rᵃ, -S(=O)₂NRᶜRᵈ, -NRᶜRᵈ, -NRᵇC(=O)NRᶜRᵈ, -NRᵇC(=O)Rᵃ, -NRᵇC(=O)ORᵇ, -NRᵇS(=O)₂Rᵃ, -C(=O)Rᵃ, -C(=O)ORᵇ, -C(=O)NRᶜRᵈ, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo, C₁-C₆ heteroalquilo, C₂-C₆ alquenilo, C₂-C₆ alquinilo, cicloalquilo, heterocicloalquilo, arilo o heteroarilo; en donde el alquilo, alquenilo, alquenilo, cicloalquilo, heterocicloalquilo, arilo y heteroarilo están opcionalmente e independientemente sustituidos con una o más R⁹ᵃ; o dos R⁹ en el mismo átomo se toman conjuntamente para formar un oxo; cada R⁹ᵃ es independientemente halógeno, -CN, -NO₂, -OH, -ORᵃ, -OC(=O)Rᵃ, -OC(=O)ORᵇ, -OC(=O)NRᶜRᵈ, -SH, -SRᵃ, -S(=O)Rᵃ, -S(=O)₂Rᵃ, -S(=O)₂NRᶜRᵈ, -NRᶜRᵈ, -NRᵇC(=O)NRᶜRᵈ, -NRᵇC(=O)Rᵃ, -NRᵇC(=O)ORᵇ, -NRᵇS(=O)₂Rᵃ, -C(=O)Rᵃ, -C(=O)ORᵇ, -C(=O)NRᶜRᵈ, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo, C₁-C₆ heteroalquilo, C₂-C₆ alquenilo, C₂-C₆ alquinilo, cicloalquilo, heterocicloalquilo, arilo o heteroarilo; o dos R⁹ᵃ en el mismo átomo se toman conjuntamente para formar un oxo; n es 0 - 4; cada Rᵃ es independientemente C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆aminoalquilo, C₁-C₆ heteroalquilo, C₂-C₆ alquenilo, C₂-C₆ alquinilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, C₁-C₆ alquilen(cicloalquilo), C₁-C₆ alquilen(heterocicloalquilo), C₁-C₆ alquilen(arilo) o C₁-C₆ alquilen(heteroarilo); en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, heterocicloalquilo, arilo y heteroarilo está independientemente opcionalmente sustituido con uno o más R; cada Rᵇ es independientemente hidrógeno, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo, C₁-C₆ heteroalquilo, C₂-C₆ alquenilo, C₂-C₆ alquinilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, C₁-C₆ alquilen(cicloalquilo), C₁-C₆ alquilen(heterocicloalquilo), C₁-C₆ alquilen(arilo) o C₁-C₆ alquilen(heteroarilo); en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, heterocicloalquilo, arilo y heteroarilo está independientemente, opcionalmente sustituido con uno o más R; cada Rᶜ y Rᵈ son independientemente hidrógeno, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo, C₁-C₆ heteroalquilo, C₂-C₆ alquenilo, C₂-C₆ alquinilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, C₁-C₆ alquilen(cicloalquilo), C₁-C₆ alquilen(heterocicloalquilo), C₁-C₆ alquilen(arilo) o C₁-C₆ alquilen(heteroarilo); en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, heterocicloalquilo, arilo y heteroarilo está independientemente, opcionalmente sustituido con uno o más R; o Rᶜ y Rᵈ se toman conjuntamente con el átomo al cual se unen para formar un heterocicloalquilo opcionalmente sustituido con uno o más R; y cada R es independientemente halógeno, -CN, -OH, -OC₁-C₆ alquilo, -S(=O)C₁-C₆alquilo, -S(=O)₂C₁-C₆ alquilo, - S(=O)₂NH₂, -S(=O)₂NHC₁-C₆ alquilo, -S(=O)₂N(C₁-C₆ alquilo)₂, -NH₂, -NHC₁-C₆ alquilo, -N(C₁-C₆ alquilo)₂, -NHC(=O)OC₁-C₆ alquilo, -C(=O)C₁-C₆ alquilo, -C(=O)OH, -C(=O)OC₁-C₆ alquilo, -C(=O)NH₂, -C(=O)N(C₁-C₆ alquilo)₂, -C(=O)NHC₁-C₆ alquilo, C₁-C₆ alquilo, C₁-C₆ haloalquilo, C₁-C₆ hidroxialquilo, C₁-C₆ aminoalquilo, o C₁-C₆ heteroalquilo; o dos R en el mismo átomo se toman conjuntamente para formar un oxo.
ARP220102947A 2021-10-28 2022-10-28 Inhibidores de la proteína que contiene el dominio de prolil hidroxilasa (phd) y usos de los mismos AR127500A1 (es)

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TW202332677A (zh) 2021-10-28 2023-08-16 香港商英科智能有限公司 含脯胺醯羥化酶結構域之蛋白質(phd)抑制劑及其用途

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