AR112264A1 - Derivados de oxoftalazina y oxocinolina como antagonistas de los receptores s1p, composición farmacéutica que los comprende y su uso para el tratamiento de enfermedades fibróticas, autoinmunes y proliferativas - Google Patents

Derivados de oxoftalazina y oxocinolina como antagonistas de los receptores s1p, composición farmacéutica que los comprende y su uso para el tratamiento de enfermedades fibróticas, autoinmunes y proliferativas

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AR112264A1
AR112264A1 ARP180101874A AR112264A1 AR 112264 A1 AR112264 A1 AR 112264A1 AR P180101874 A ARP180101874 A AR P180101874A AR 112264 A1 AR112264 A1 AR 112264A1
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alkyl
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Galapagos Nv
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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
    • A61K31/495—Heterocyclic 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
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
    • 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
    • C07D403/14—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 three or more hetero rings
    • 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
    • A61K31/437—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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D401/14—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 three or more hetero rings
    • 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
    • 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
    • C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Compuestos antagonistas de los receptores de esfingosina 1-fosfato (S1P), composiciones farmacéuticas que los comprenden, para la profilaxis y/o el tratamiento de enfermedades que comprenden enfermedades fibróticas, enfermedades inflamatorias, enfermedades respiratorias, enfermedades autoinmunes, enfermedades metabólicas, enfermedades cardiovasculares y/o enfermedades proliferativas. Reivindicación 1: Un compuesto, o una sal farmacéuticamente aceptable, o un solvato o la sal farmacéuticamente aceptable de un solvato del mismo, de acuerdo con la fórmula (1), en donde cada A¹, A² y A³ se selecciona de manera independiente entre C y N, con la condición de que A¹, A² y A³ no sean simultáneamente C o N; cada R¹ se selecciona de manera independiente entre: alquilo C₁₋₄, alcoxi C₁₋₄, cicloalquilo C₃₋₆, heteroarilo monocíclico de 4 - 7 miembros que comprende 1, 2 ó 3 heteroátomos seleccionados de manera independiente de N, O, o S, opcionalmente sustituido con uno o dos grupos =O, -S(O)₂alquilo C₁₋₄, -CN, -C(=O)NH₂, y halo; el subíndice n es 0, 1 ó 2; Cy es un heteroarilo bicíclico fusionado 5 - 6 de 9 miembros ligado a un anillo de 5 miembros, que comprende 1, 2 ó 3 átomos de N, donde el heteroarilo está sustituido con un grupo R³ y un grupo R⁴ᵃ, y opcionalmente sustituido además con un halo u OH; R³ es alcoxi C₁₋₆ opcionalmente sustituido con uno o varios, seleccionados de manera independiente, halo, alcoxi C₁₋₄, o cicloalquilo C₃₋₇ opcionalmente sustituido con un alquilo C₁₋₄, halo o -CN; R⁴ᵃ es alquilo C₁₋₄ opcionalmente sustituido con uno o varios halo, halo, o CN; L está ausente o es -CR⁵ᵃR⁵ᵇ-; R² es -C(=O)OH, -C(=O)NR⁶ᵃR⁶ᵇ, -C(O)NHS(O)₂-alquilo C₁₋₄, -C(O)NHS(O)₂-cicloalquilo C₃₋₇, -Cy¹, o -C(=O)Cy²; cada R⁵ᵃ y R⁵ᵇ se selecciona de manera independiente entre H, alquilo C₁₋₄ opcionalmente sustituido con uno, dos o tres halo o -NR⁸ᵃR⁸ᵇ, y alcoxi C₁₋₄; cada R⁶ᵃ y R⁶ᵇ se selecciona, de manera independiente, de H, alquilo C₁₋₆ opcionalmente sustituido de uno o varios, seleccionados de manera independiente, OH, -CN, halo, alcoxi C₁₋₄, heterocicloalquilo monocíclico de 4 - 6 miembros que comprende uno dos heteroátomos seleccionados de N, O y S, opcionalmente sustituido con un -CH₂-OH, -S(O)₂alquilo C₁₋₄, -S(O)₂NH₂, -C(O)NR⁹ᵃR⁹ᵇ, o cicloalquilo C₃₋₇ opcionalmente sustituido con OH o halo; alcoxi C₁₋₄, cicloalquilo C₃₋₇ opcionalmente sustituido con uno o varios OH, y heterocicloalquilo monocíclico de 4 - 6 miembros que comprende uno o dos heteroátomos seleccionados de N, O y S, opcionalmente sustituido con uno o dos oxo; Cy¹ es cicloalquilo C₃₋₇ monocíclico, opcionalmente sustituido con un -C(=O)OH, heterocicloalquilo monocíclico de 4 - 6 miembros que comprende uno o dos heteroátomos seleccionados de N, O y S, opcionalmente sustituido con uno o dos alquilo C₁₋₄ opcionalmente sustituido con un -C(=O)OH; Cy² es heterocicloalquilo monocíclico de 4 - 7 miembros ligado a N que comprende por lo menos un átomo de N, y opcionalmente uno o dos heteroátomos seleccionados de N, O y S, opcionalmente sustituido con uno o varios OH, oxo, -CN, halo, alcoxi C₁₋₄, alquilo C₁₋₄ opcionalmente sustituido con uno o varios, seleccionados de manera independiente, halo, OH, cicloalquilo C₃₋₇, -S(O)₂alquilo C₁₋₄, o -NR⁷ᵃR⁷ᵇ; o heterocicloalquilo espirocíclico de 7 - 9 miembros ligado a N que comprende por lo menos un átomo de N, y opcionalmente uno o dos heteroátomos seleccionados de N, O y S, opcionalmente sustituido con uno o varios halo; cada R⁷ᵃ, R⁷ᵇ, R⁸ᵃ, R⁸ᵇ, R⁹ᵃ y R⁹ᵇ se selecciona de manera independiente entre H y alquilo C₁₋₄; con la condición de que cuando L está ausente, A¹ y A² son C, A³ es N, y R² es COOH, R³ es alcoxi C₁₋₆ no sustituido o alcoxi C₁₋₆ sustituido con halógeno, entonces no COOH; y cuando A¹ y A² son N, A³ es C, y R⁴ᵃ es -CH₃, entonces R³ no es alcoxi C₁₋₄ no sustituido.
ARP180101874 2017-07-06 2018-07-05 Derivados de oxoftalazina y oxocinolina como antagonistas de los receptores s1p, composición farmacéutica que los comprende y su uso para el tratamiento de enfermedades fibróticas, autoinmunes y proliferativas AR112264A1 (es)

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GBGB1710851.5A GB201710851D0 (en) 2017-07-06 2017-07-06 Novel compounds and pharmaceutical compositions thereof for the treatment of fibrosis

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US (1) US20210315893A1 (es)
EP (1) EP3649119B1 (es)
JP (1) JP2020525508A (es)
KR (1) KR20200027543A (es)
CN (1) CN110869359A (es)
AR (1) AR112264A1 (es)
AU (1) AU2018296398A1 (es)
BR (1) BR112020000029A2 (es)
CA (1) CA3069038A1 (es)
CO (1) CO2020000056A2 (es)
GB (1) GB201710851D0 (es)
IL (1) IL271807A (es)
MA (1) MA52118A (es)
MX (1) MX2019015350A (es)
RU (1) RU2020105248A (es)
SG (1) SG11202000032PA (es)
TW (1) TW201920167A (es)
WO (1) WO2019007696A1 (es)

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KR20200027543A (ko) 2020-03-12
US20210315893A1 (en) 2021-10-14
WO2019007696A1 (en) 2019-01-10
MX2019015350A (es) 2020-02-20
CN110869359A (zh) 2020-03-06
JP2020525508A (ja) 2020-08-27
MA52118A (fr) 2021-05-19
CA3069038A1 (en) 2019-01-10
BR112020000029A2 (pt) 2020-07-14
EP3649119A1 (en) 2020-05-13
CO2020000056A2 (es) 2020-01-17
TW201920167A (zh) 2019-06-01
EP3649119B1 (en) 2021-11-03
SG11202000032PA (en) 2020-02-27
GB201710851D0 (en) 2017-08-23
IL271807A (en) 2020-02-27
RU2020105248A (ru) 2021-08-06

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