AR120684A1 - INHIBIDORES DE HIF-2a - Google Patents

INHIBIDORES DE HIF-2a

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Publication number
AR120684A1
AR120684A1 ARP200103396A ARP200103396A AR120684A1 AR 120684 A1 AR120684 A1 AR 120684A1 AR P200103396 A ARP200103396 A AR P200103396A AR P200103396 A ARP200103396 A AR P200103396A AR 120684 A1 AR120684 A1 AR 120684A1
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AR
Argentina
Prior art keywords
group
independently selected
alkyl
haloalkyl
alkoxy
Prior art date
Application number
ARP200103396A
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English (en)
Inventor
Jeremy Thomas Andre Fournier
Joel Worley Beatty
Samuel Lawrie Drew
Anh Thu Tran
Yongli Su
Brandon Reid Rosen
Debashis Mandal
Erick Allen Lindsey
Steven Donald Jacob
Tezcan Guney
Kenneth Victor Lawson
Manmohan Reddy Leleti
Guillaume Mata
Jay Patrick Powers
Xuelei Yan
Original Assignee
Arcus Biosciences Inc
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Application filed by Arcus Biosciences Inc filed Critical Arcus Biosciences Inc
Publication of AR120684A1 publication Critical patent/AR120684A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56Benzopyrazoles; Hydrogenated benzopyrazoles
    • 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
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • A61K31/4161,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • 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
    • A61K31/437Heterocyclic 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
    • 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/4709Non-condensed quinolines and containing further heterocyclic rings
    • 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
    • A61K31/4965Non-condensed pyrazines
    • A61K31/497Non-condensed pyrazines containing further heterocyclic rings
    • 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
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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 chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/12Heterocyclic 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 chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • 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

Abstract

En el presente documento se describen compuestos que inhiben HIF-2a y composiciones que contienen los compuestos y métodos para sintetizar los compuestos. También se describe el uso de tales compuestos y composiciones para el tratamiento de una diversidad de enfermedades, trastornos y afecciones, incluidos los trastornos relacionados con el cáncer y con el sistema inmunitario que están mediados, al menos en parte, por HIF-2a. Reivindicación 1: Un compuesto representado por la fórmula (1) o una sal farmacéuticamente aceptable de este, caracterizado por que, los enlaces discontinuos son enlaces simples y dobles concordantes con los grupos proporcionados para Y¹, Y² e Y³; X¹ es CR¹ o N; X² es CR² o N; X³ es CR³ o N; Y se selecciona del grupo que consiste en -O-, -C(Rᵃ)(Rᵇ)-, -N(Rᵃ)-, -C(Rᵃ)(Rᵇ)-N(Rᵃ)-, -S- y -S(O)₂-; Y¹, Y² y Y³ se seleccionan cada uno independientemente del grupo que consiste en CR⁵, NR⁶ y N, donde uno de Y¹, Y² y Y³ es N, y uno de Y¹, Y² y Y³ es NR⁶; R¹ y R² son cada uno miembros seleccionados independientemente del grupo que consiste en H, halógeno, CN, -NO₂, alquilo C₁₋₄, haloalquilo C₁₋₄ y haloalcoxi C₁₋₄; R³ es un miembro seleccionado del grupo que consiste en H, halógeno, CN, -NO₂, -S(O)₂Rᵃ, -C(O)NRᵃRᵇ, -P(O)RᵃRᵇ, alquilo C₁₋₈, alcoxi C₁₋₈, haloalquilo C₁₋₈, haloalcoxi C₁₋₄, arilo C₆₋₁₀ y heteroarilo de 5 a 10 miembros que tiene de 1 a 4 heteroátomos en los vértices del anillo seleccionados independientemente del grupo que consiste en N, O y S; cuando cada uno de R¹, R² y R³ están presentes, al menos uno es diferente de H; R⁴ es un miembro seleccionado del grupo que consiste en alquilo C₁₋₈, alcoxi C₁₋₈, cicloalquilo C₃₋₈, arilo C₆₋₁₀ y heteroarilo de 6 miembros que tiene de 1 a 4 heteroátomos en los vértices del anillo seleccionados independientemente del grupo que consiste en N, O y S; cada R⁵ es un miembro seleccionado del grupo que consiste en H, -NO₂, -S(O)₂Rᵃ, -S(O)₂NRᵃRᵇ, -S(O)(NH)Rᵃ, -C(O)Rᵃ, -C(O)NRᵃRᵇ, CN, halógeno, -P(O)RᵃRᵇ, alquilo C₁₋₈, alcoxi C₁₋₈, alcoximetilo C₁₋₈, haloalquilo C₁₋₈, hidroxialquilo C₁₋₈, -NRᵃRᵇ, arilo C₆₋₁₀ y heteroarilo de 5 a 10 miembros que tiene de 1 a 4 heteroátomos en los vértices del anillo seleccionados independientemente del grupo que consiste en N, O y S; cada R⁶ es un miembro seleccionado del grupo que consiste en H, alquilo C₁₋₈, arilo C₆₋₁₀ y heteroarilo de 5 a 10 miembros que tiene de 1 a 4 heteroátomos en los vértices del anillo seleccionados independientemente del grupo que consiste en N, O y S; donde cada Rᵃ y Rᵇ se seleccionan independientemente del grupo que consiste en H, alquilo C₁₋₈, alcoxi C₁₋₈, haloalquilo C₁₋₈ y haloalcoxi C₁₋₈ e hidroxialquilo C₁₋₈; y para cada R⁴, R⁵ y R⁶, cada cicloalquilo C₃₋₈, arilo C₆₋₁₀ y heteroarilo esté o no sustituido con uno a cinco Rᶜ; donde cada Rᶜ se selecciona independientemente del grupo que consiste en halógeno, CN, -NO₂, alquilo C₁₋₈, alcoxi C₁₋₈, haloalquilo C₁₋₈, -S(O)₂Rᵈ, -C(O)NRᵈRᵉ y -P(O)RᵈRᵉ; y Rᵈ y Rᵉ se seleccionan cada uno independientemente del grupo que consiste en H, alquilo C₁₋₈, alcoxi C₁₋₈, haloalquilo C₁₋₈ y haloalcoxi C₁₋₈.
ARP200103396A 2019-12-04 2020-12-04 INHIBIDORES DE HIF-2a AR120684A1 (es)

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US201962943632P 2019-12-04 2019-12-04

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AR120684A1 true AR120684A1 (es) 2022-03-09

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US (1) US20230024438A1 (es)
EP (1) EP4069212A4 (es)
JP (1) JP2023504623A (es)
KR (1) KR20220110524A (es)
CN (1) CN114760994A (es)
AR (1) AR120684A1 (es)
AU (1) AU2020395783A1 (es)
CA (1) CA3163338A1 (es)
TW (1) TW202134216A (es)
WO (1) WO2021113436A1 (es)

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CA3173831A1 (en) 2020-03-19 2021-09-23 Arcus Biosciences, Inc. Tetralin and tetrahydroquinoline compounds as inhibitors of hif-2alpha
TW202313603A (zh) 2021-05-21 2023-04-01 美商阿克思生物科學有限公司 Axl抑制劑化合物
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WO2024015251A1 (en) 2022-07-15 2024-01-18 Arcus Biosciences, Inc. Inhibitors of hpk1 and methods of use thereof
WO2024020034A1 (en) 2022-07-20 2024-01-25 Arcus Biosciences, Inc. Cbl-b inhibitors and methods of use thereof
WO2024059142A1 (en) 2022-09-14 2024-03-21 Arcus Biosciences, Inc. Dispersions of etrumadenant
CN117800944A (zh) * 2022-09-30 2024-04-02 苏州阿尔脉生物科技有限公司 吡啶酰胺类衍生物、包含其的药物组合物及其医药用途
WO2024081385A1 (en) 2022-10-14 2024-04-18 Arcus Biosciences, Inc. Hpk1 inhibitors and methods of use thereof

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CN114760994A (zh) 2022-07-15
TW202134216A (zh) 2021-09-16
EP4069212A4 (en) 2024-03-06
JP2023504623A (ja) 2023-02-06
US20230024438A1 (en) 2023-01-26
AU2020395783A1 (en) 2022-06-09
KR20220110524A (ko) 2022-08-08
WO2021113436A1 (en) 2021-06-10
EP4069212A1 (en) 2022-10-12
CA3163338A1 (en) 2021-06-10

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