AR100702A1 - Compuestos inhibidores de quinasa de unión tank - Google Patents

Compuestos inhibidores de quinasa de unión tank

Info

Publication number
AR100702A1
AR100702A1 ARP150101733A ARP150101733A AR100702A1 AR 100702 A1 AR100702 A1 AR 100702A1 AR P150101733 A ARP150101733 A AR P150101733A AR P150101733 A ARP150101733 A AR P150101733A AR 100702 A1 AR100702 A1 AR 100702A1
Authority
AR
Argentina
Prior art keywords
nrarb
nrac
cycloalkyl
ora
alkyl
Prior art date
Application number
ARP150101733A
Other languages
English (en)
Original Assignee
Gilead Sciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of AR100702A1 publication Critical patent/AR100702A1/es

Links

Classifications

    • 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
    • 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
    • A61K31/495—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
    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
    • A61K31/495—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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Obesity (AREA)
  • Immunology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Neurosurgery (AREA)
  • Emergency Medicine (AREA)
  • Dermatology (AREA)
  • Cardiology (AREA)
  • Pulmonology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Se divulgan compuestos, métodos para su uso y preparación, que pueden inhibir o modular la actividad de la quinasa de unión TANK (TBK1), la quinasa I-Kappa-B (IKKe, IKBKE) útiles en el tratamiento, por ejemplo, del cáncer. Reivindicación 1: Un compuesto de la fórmula (1), donde: A es un anillo arilo o heteroarilo de 6 miembros; X¹ es CR² o N; X² y X³ son, de manera independiente, CR³ o N, siempre que, como máximo, solo uno de X² y X³ sea N; R¹ se selecciona del grupo que consiste en H, C₁₋₆ alquilo, C₂₋₆ alquenilo, C₂₋₆ alquinilo, -ORᵃ, -C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃRᵇ, -CN, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᵃ, -S(O)₂NRᵃRᵇ, -NRᵃS(O)₂Rᵇ, donde cada C₁₋₆ alquilo, C₂₋₆ alquenilo y C₂₋₆ alquinilo está opcionalmente sustituido con de uno a cinco grupos R²⁰; o R¹ tiene la estructura de fórmula (2) donde B se selecciona del grupo que consiste en C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 12 miembros; R² se selecciona del grupo que consiste en H, C₁₋₆ alquilo, C₃₋₁₀ cicloalquilo, heterociclilo de 3 - 12 miembros, C₁₋₆ heteroalquilo, C₁₋₆ haloalquilo, C₂₋₆ alquenilo, C₂₋₆ alquinilo, -NRᵃRᵇ, halógeno, -CN, -NO₂, -ORᵃ, -C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᵃ, -S(O)₂NRᵃRᵇ y -NRᵃS(O)₂Rᵇ; cada R³ se selecciona de manera independiente del grupo que consiste en H, C₁₋₆ alquilo, C₃₋₁₀ cicloalquilo, heterociclilo de 3 - 12 miembros, C₁₋₆ heteroalquilo, C₁₋₆ haloalquilo, C₂₋₆ alquenilo, C₂₋₆ alquinilo, -NRᵃRᵇ, halógeno, -CN, -NO₂, -ORᵃ, -C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᵃ, -S(O)₂NRᵃRᵇ y -NRᵃS(O)₂Rᵇ; cada R⁴ se selecciona de manera independiente del grupo que consiste en H, C₁₋₆ alquilo, C₁₋₆ heteroalquilo, C₁₋₆ haloalquilo, C₂₋₆ alquenilo, C₂₋₆ alquinilo, -NRᵃRᵇ, halógeno, C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᵃ, -S(O)₂NRᵃRᵇ, -NRᵃS(O)₂Rᵇ, -N₃, -CN, -NO₂ y -ORᵃ; R⁵ se selecciona del grupo que consiste en H, C₁₋₆ alquilo, C₁₋₆ heteroalquilo, -NRᵃRᵇ, halógeno, C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᵃ, -S(O)₂NRᵃRᵇ, -NRᵃS(O)₂Rᵇ, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de 5 - 10 miembros, heterociclilo de 3 - 12 miembros y -O-R⁹, donde cada C₁₋₆ alquilo, C₁₋₆ heteroalquilo, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 12 miembros está opcionalmente sustituido con de uno a cinco grupos R²⁰; o R⁵ y un R⁴ se toman juntos para formar un arilo fusionado C₆, heteroarilo de 5 - 10 miembros, heterociclilo de 5 - 10 miembros o C₃₋₆ cicloalquilo cada uno, opcionalmente sustituido con uno a cinco grupos R²⁰; R⁶ es -CN ubicado en la posición meta (3) con respecto al punto de unión del anillo A; R⁷ se selecciona del grupo que consiste en H, C₁₋₆ alquilo, C₂₋₆ alquenilo, C₂₋₆ alquinilo, C₁₋₆ heteroalquilo, -NRᵃRᵇ, halógeno, C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᵃ, -S(O)₂NRᵃRᵇ, -NRᵃS(O)₂Rᵇ, -N₃, -CN, -NO₂, -ORᵃ, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 12 miembros, donde cada C₁₋₆ alquilo, C₂₋₆ alquenilo, C₂₋₆ alquinilo, C₁₋₆ heteroalquilo, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 12 miembros está opcionalmente sustituido con 1 - 5 grupos R²⁰; cada R⁸ se selecciona de manera independiente del grupo que consiste en H, C₁₋₆ alquilo, C₁₋₆ heteroalquilo, C₁₋₆ haloalquilo, C₁₋₆ hidroxialquilo, C₂₋₆ alquenilo, C₂₋₆ alquinilo, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 12 miembros, -NRᵃRᵇ, halógeno, -C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᶜ, -S(O)₂NRᵃRᵇ, -NRᵃS(O)₂Rᵇ, -N₃, -CN, -NO₂ y -ORᵃ, donde cada C₁₋₆ alquilo, C₁₋₆ heteroalquilo, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de 5 - 10 miembros y heterociclilo de 3 - 12 miembros está opcionalmente sustituido con de uno a cinco grupos R²⁰; o R⁷ y R⁸ se toman juntos para formar un C₃₋₁₀ cicloalquilo fusionado, espiro o puenteado o heterociclilo de 3 - 12 miembros, que están opcionalmente sustituidos con 1 - 5 grupos R²⁰; R⁹ es C₁₋₆ alquilo, heterociclilo de 3 - 12 miembros, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de 5 - 10 miembros o heterociclilo de 3 - 12 miembros, cada uno de los cuales esté opcionalmente sustituido con de uno a cinco grupos R²⁰; n es 0 - 2; m es 0 - 3; cada R²⁰ es, de manera independiente, C₁₋₆ alquilo, C₃₋₁₀ cicloalquilo, C₁₋₆ heteroalquilo, heterociclilo de 3 - 12 miembros, C₆₋₁₀ arilo, heteroarilo de 5 - 10 miembros, halógeno, oxo, -ORᵃ, -C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃRᵇ, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᵃ, -S(O)₂NRᵃRᵇ, -NRᵃS(O)₂Rᵇ, -N₃, -CN, o -NO₂, o dos grupos R²⁰ pueden unirse entre sí para formar un C₃₋₁₀ cicloalquilo fusionado, espiro o puenteado o anillo heterociclilo de 3 - 12 miembros, donde cada C₁₋₆ alquilo, C₃₋₁₀ cicloalquilo, C₁₋₆ heteroalquilo, heterociclilo de 3 - 12 miembros, C₆₋₁₀ arilo, heteroarilo de 5 - 10 miembros está opcionalmente sustituido con de uno a cinco halógeno, oxo, -ORᵃ, -C(O)Rᵃ, -C(O)ORᵃ, -C(O)NRᵃRᵇ, -OC(O)NRᵃRᵇ, -NRᵃRᵇ, -NRᵃC(O)Rᵇ, -NRᵃC(O)ORᵇ, -S(O)₀₋₂Rᵃ, -S(O)₂NRᵃRᵇ, -NRᵃS(O)₂Rᵇ, -N₃, -CN, o -NO₂; cada R²¹ es, de manera independiente, C₁₋₆ alquilo, C₃₋₁₀ cicloalquilo, C₁₋₆ heteroalquilo, heterociclilo de 3 - 12 miembros, C₆₋₁₀ arilo, heteroarilo de 5 - 10 miembros, hidroxilo, amino, C₁₋₆ alquilamino, -CN o halógeno; y cada Rᵃ y Rᵇ es, de manera independiente, H; o C₁₋₆ alquilo, C₃₋₁₀ cicloalquilo, C₁₋₆ heteroalquilo, heterociclilo de 3 - 12 miembros, C₆₋₁₀ arilo, heteroarilo de 5 - 10 miembros, cada uno de los cuales está opcionalmente sustituido con de uno a cinco grupos R²¹; o Rᵃ y Rᵇ junto con los átomos a los cuales están unidos forman un heterociclilo de 3 - 12 miembros opcionalmente sustituido con uno a cinco grupos R²¹; con la condición de que si R¹ es H, entonces todos los grupos R² y R³ son H; o una de sus sales farmacéuticamente aceptables.
ARP150101733A 2014-06-03 2015-06-01 Compuestos inhibidores de quinasa de unión tank AR100702A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201462007322P 2014-06-03 2014-06-03

Publications (1)

Publication Number Publication Date
AR100702A1 true AR100702A1 (es) 2016-10-26

Family

ID=53546688

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP150101733A AR100702A1 (es) 2014-06-03 2015-06-01 Compuestos inhibidores de quinasa de unión tank

Country Status (19)

Country Link
US (2) US10072001B2 (es)
EP (1) EP3152210B1 (es)
JP (2) JP6378785B2 (es)
KR (2) KR101926245B1 (es)
CN (1) CN106459044A (es)
AR (1) AR100702A1 (es)
AU (2) AU2015271837B2 (es)
BR (1) BR112016028288A2 (es)
CA (1) CA2951126A1 (es)
EA (1) EA031757B1 (es)
ES (1) ES2961577T3 (es)
HK (1) HK1231475A1 (es)
IL (1) IL248888A0 (es)
MA (1) MA40058A (es)
MX (1) MX2016015862A (es)
NZ (1) NZ726317A (es)
SG (1) SG11201609570SA (es)
TW (1) TW201613916A (es)
WO (1) WO2015187684A1 (es)

Families Citing this family (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104736569A (zh) 2012-01-12 2015-06-24 耶鲁大学 通过e3泛素连接酶增强靶蛋白质及其他多肽降解的化合物和方法
GB201311891D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compound
GB201311888D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compounds
TW201613916A (en) 2014-06-03 2016-04-16 Gilead Sciences Inc TANK-binding kinase inhibitor compounds
US10071164B2 (en) 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use
ES2881195T3 (es) 2014-09-26 2021-11-29 Gilead Sciences Inc Derivados de aminotriazina útiles como compuestos inhibidores de quinasas que se unen a TANK
WO2016077595A1 (en) 2014-11-12 2016-05-19 The General Hospital Corporation Methods for treating neurodegenerative diseases
US20170327469A1 (en) 2015-01-20 2017-11-16 Arvinas, Inc. Compounds and methods for the targeted degradation of androgen receptor
KR102564925B1 (ko) 2015-01-20 2023-08-07 아비나스 오퍼레이션스, 인코포레이티드 안드로겐 수용체의 표적화된 분해를 위한 화합물 및 방법
CA2979070A1 (en) 2015-03-18 2016-09-22 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
US20180147202A1 (en) 2015-06-05 2018-05-31 Arvinas, Inc. TANK-BINDING KINASE-1 PROTACs AND ASSOCIATED METHODS OF USE
US10772962B2 (en) 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
DK3362449T3 (da) * 2015-10-13 2021-07-19 Inst Nat Sante Rech Med Sibirilin-derivater til anvendelse til at forebygge og/eller behandle lidelser associeret med cellulær nekroptose
MA43373A (fr) 2015-12-04 2018-10-10 Global Blood Therapeutics Inc Régimes posologiques pour 2-hydroxy-6-((2- (1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)méthoxy)benzaldéhyde
US10316049B2 (en) 2015-12-17 2019-06-11 Gilead Sciences, Inc. Tank-binding kinase inhibitor compounds
US10894784B2 (en) 2015-12-18 2021-01-19 Bayer Pharma Aktiengesellschaft Heteroarylbenzimidazole compounds
WO2017173451A1 (en) * 2016-04-01 2017-10-05 The General Hospital Corporation Targeting innate immune signaling in neuroinflammation and neurodegeneration
AU2017250302B2 (en) 2016-04-15 2021-01-21 Blueprint Medicines Corporation Inhibitors of activin receptor-like kinase
WO2017207534A1 (en) 2016-06-03 2017-12-07 Bayer Pharma Aktiengesellschaft Substituted heteroarylbenzimidazole compounds
EP3512842B1 (en) 2016-09-15 2024-01-17 Arvinas, Inc. Indole derivatives as estrogen receptor degraders
AU2017341723B2 (en) 2016-10-11 2021-12-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
WO2018102067A2 (en) 2016-11-01 2018-06-07 Arvinas, Inc. Tau-protein targeting protacs and associated methods of use
SI3689868T1 (sl) 2016-12-01 2024-02-29 Arvinas Operations, Inc. Derivati tetrahidronaftalena in tetrahidroizokinolina kot razgrajevalci estrogenskih receptorjev
BR112019012878A2 (pt) 2016-12-23 2019-11-26 Arvinas Operations Inc compostos e métodos para a degradação alvo de polipeptídos de fibrossarcoma rapidamente acelerados
WO2018118598A1 (en) 2016-12-23 2018-06-28 Arvinas, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
BR112019012682A2 (pt) 2016-12-23 2019-12-17 Arvinas Operations Inc moléculas quiméricas visando a proteólise de egfr e métodos associados de uso
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
KR20230140606A (ko) 2017-01-26 2023-10-06 아비나스 오퍼레이션스, 인코포레이티드 에스트로겐 수용체 단백질 분해 조절제 및 관련 사용 방법
SG11201908240YA (en) 2017-03-31 2019-10-30 Dana Farber Cancer Inst Inc Methods for evaluating tumor cell spheroids using 3d microfluidic cell culture device
ES2931537T3 (es) 2017-10-18 2022-12-30 Blueprint Medicines Corp Pirrolopiridinas sustituidas como inhibidores de la quinasa similar al receptor de activina
KR20190043437A (ko) 2017-10-18 2019-04-26 씨제이헬스케어 주식회사 단백질 키나제 억제제로서의 헤테로고리 화합물
WO2019099926A1 (en) 2017-11-17 2019-05-23 Arvinas, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides
JP2021512153A (ja) 2018-01-26 2021-05-13 イエール ユニバーシティ タンパク質分解のイミド系モジュレーターおよび使用方法
MX2020010420A (es) 2018-04-04 2020-12-11 Arvinas Operations Inc Moduladores de la proteólisis y métodos asociados de uso.
WO2020041331A1 (en) 2018-08-20 2020-02-27 Arvinas Operations, Inc. Proteolysis targeting chimeric (protac) compound with e3 ubiquitin ligase binding activity and targeting alpha-synuclein protein for treating neurodegenerative diseases
JP2022540935A (ja) 2019-07-17 2022-09-20 アルビナス・オペレーションズ・インコーポレイテッド タウタンパク質標的化化合物および関連する使用方法
WO2021127443A1 (en) 2019-12-19 2021-06-24 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
CN113549065B (zh) * 2020-04-24 2022-05-10 成都先导药物开发股份有限公司 作为JAK抑制剂的吡咯并[2,3-b]吡啶衍生物
CN114622017A (zh) * 2020-12-14 2022-06-14 中山大学孙逸仙纪念医院 Isg15、isg15诱导的巨噬细胞及其分泌物在肿瘤治疗中的应用
IL305860A (en) 2021-04-16 2023-11-01 Arvinas Operations Inc BCL6 proteolysis modulators and related methods of use
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use
WO2024088377A1 (zh) * 2022-10-27 2024-05-02 香港科技大学 嘧啶并吡咯类似物

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3845770A (en) 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US4326525A (en) 1980-10-14 1982-04-27 Alza Corporation Osmotic device that improves delivery properties of agent in situ
US5364620A (en) 1983-12-22 1994-11-15 Elan Corporation, Plc Controlled absorption diltiazem formulation for once daily administration
US5023252A (en) 1985-12-04 1991-06-11 Conrex Pharmaceutical Corporation Transdermal and trans-membrane delivery of drugs
US4992445A (en) 1987-06-12 1991-02-12 American Cyanamid Co. Transdermal delivery of pharmaceuticals
US5001139A (en) 1987-06-12 1991-03-19 American Cyanamid Company Enchancers for the transdermal flux of nivadipine
US4902514A (en) 1988-07-21 1990-02-20 Alza Corporation Dosage form for administering nilvadipine for treating cardiovascular symptoms
GB0402809D0 (en) 2004-02-09 2004-03-10 Glaxo Group Ltd Chemical compounds
ES2605792T3 (es) 2004-05-13 2017-03-16 Icos Corporation Quinazolinona usada como inhibidor de la fosfatidilinositol 3-quinasa delta humana
BRPI0611863B1 (pt) * 2005-06-22 2021-11-23 Plexxikon, Inc Composto, bem como composição e kit compreendendo o mesmo, composto intermediário na preparação do mesmo, método para tratamento e uso do mesmo
CL2008000192A1 (es) * 2007-01-23 2008-07-25 Palau Pharma Sa Compuestos derivados de purina sustituidos; proceso de preparacion; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como rechazo a transplantes, leucemias, diabetes, entre otras.
MX2009009792A (es) 2007-03-12 2009-09-23 Cytopia Res Pty Ltd Compuestos de fenil amino pirimidina y usos de los mismos.
WO2009030890A1 (en) 2007-09-03 2009-03-12 University Court Of The University Of Dundee Pyrimidine compounds for the treatment of cancer, septic shock and/or primary open angle glaucoma
EP2231624A4 (en) 2007-12-21 2011-07-06 Progenics Pharm Inc TRIAZINE AND CORRESPONDING COMPOUNDS WITH ANTIVIRAL EFFECT, COMPOSITIONS AND METHOD THEREFOR
AR070127A1 (es) 2008-01-11 2010-03-17 Novartis Ag Pirrolo - pirimidinas y pirrolo -piridinas
GB0805477D0 (en) 2008-03-26 2008-04-30 Univ Nottingham Pyrimidines triazines and their use as pharmaceutical agents
WO2009122180A1 (en) 2008-04-02 2009-10-08 Medical Research Council Pyrimidine derivatives capable of inhibiting one or more kinases
US8450321B2 (en) 2008-12-08 2013-05-28 Gilead Connecticut, Inc. 6-(1H-indazol-6-yl)-N-[4-(morpholin-4-yl)phenyl]imidazo-[1,2-A]pyrazin-8-amine, or a pharmaceutically acceptable salt thereof, as a SYK inhibitor
GB0903759D0 (en) 2009-03-04 2009-04-15 Medical Res Council Compound
DE102009019962A1 (de) 2009-05-05 2010-11-11 Merck Patent Gmbh 3-([1,2,3]Triazol-4-yl)-pyrrolo[2,3-b]pyridinderivate
AU2010306927A1 (en) * 2009-10-12 2012-05-31 Myrexis, Inc. Amino - pyrimidine compounds as inhibitors of TBKL and/or IKK epsilon
CN102666545B (zh) 2009-10-20 2016-04-06 塞尔卓姆有限公司 作为jak抑制剂的杂环吡唑并嘧啶类似物
GB201012105D0 (en) 2010-07-19 2010-09-01 Domainex Ltd Novel pyrimidine compounds
DE102010049877A1 (de) 2010-11-01 2012-05-03 Merck Patent Gmbh 7-((1,2,3)Triazol-4-yl)-pyrrolo(2,3) pyrazinderivate
DE102011008352A1 (de) 2011-01-12 2012-07-12 Merck Patent Gmbh 5-([1,2,3]Triazol-4-yl)-7H-pyrrolo-[2,3-d]pyrimidinderivate
DE102011009961A1 (de) 2011-02-01 2012-08-02 Merck Patent Gmbh 7-Azaindolderivate
US20140288044A1 (en) 2011-04-12 2014-09-25 Alzheimer's Institute Of America, Inc. Compositions and therapeutic uses of ikk-related kinase epsilon and tankbinding kinase 1 inhibitors
SI2714677T1 (sl) 2011-05-23 2018-12-31 Merck Patent Gmbh Piridinski in pirazinski derivati
CA2831966C (en) 2011-05-23 2016-07-19 Merck Patent Gmbh Thiazole derivatives
CN102827073A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
GB201114051D0 (en) 2011-08-15 2011-09-28 Domainex Ltd Compounds and their uses
EP2562265A1 (en) 2011-08-22 2013-02-27 Lead Discovery Center GmbH Susceptibility to selective CDK9 inhibitors
DE102011111400A1 (de) 2011-08-23 2013-02-28 Merck Patent Gmbh Bicyclische heteroaromatische Verbindungen
DE102011112978A1 (de) 2011-09-09 2013-03-14 Merck Patent Gmbh Benzonitrilderivate
DE102011119127A1 (de) 2011-11-22 2013-05-23 Merck Patent Gmbh 3-Cyanaryl-1H-pyrrolo[2.3-b]pyridin-Derivate
EP2788000B1 (en) 2011-12-06 2018-05-30 Merck Sharp & Dohme Corp. Pyrrolopyrimidines as janus kinase inhibitors
WO2013091096A1 (en) 2011-12-20 2013-06-27 Boehringer Ingelheim International Gmbh Condensed triclyclic compounds as inhibitors of hiv replication
ES2606637T3 (es) * 2012-02-09 2017-03-24 Merck Patent Gmbh Derivados de furo [3,2- b]piridina como inhibidores de TBK1 e IKK
WO2014004863A2 (en) 2012-06-27 2014-01-03 Alzheimer's Institute Of America, Inc. Compounds, compositions, and therapeutic uses thereof
GB201303109D0 (en) 2013-02-21 2013-04-10 Domainex Ltd Novel pyrimidine compounds
WO2014139328A1 (en) * 2013-03-14 2014-09-18 Abbvie Inc. Pyrrolo[2,3-b]pyridine cdk9 kinase inhibitors
CN103251600B (zh) 2013-05-27 2015-05-20 中南大学 2-氨基-4-(3′-氰基-4′-吡咯烷基)苯基嘧啶化合物的抗肿瘤应用
US10370664B2 (en) 2013-11-07 2019-08-06 University Of Southern California Use of IKK epsilon inhibitors to activate NFAT and T cell response
US10280169B2 (en) 2013-12-11 2019-05-07 Biogen Ma Inc. Biaryl bruton's tyrosine kinase inhibitors
US9598424B2 (en) 2014-03-06 2017-03-21 Takeda Pharmaceutical Company Limited Heteroarylamide inhibitors of TBK1
TW201613916A (en) 2014-06-03 2016-04-16 Gilead Sciences Inc TANK-binding kinase inhibitor compounds
ES2881195T3 (es) 2014-09-26 2021-11-29 Gilead Sciences Inc Derivados de aminotriazina útiles como compuestos inhibidores de quinasas que se unen a TANK
US9994547B2 (en) 2014-10-06 2018-06-12 Takeda Pharmaceutical Company Limited Heteroarylamide inhibitors of TBK1
AU2016287335B2 (en) 2015-06-29 2020-01-23 Merck Patent Gmbh TBK/IKKepsilon inhibitor compounds and uses thereof
US10316049B2 (en) 2015-12-17 2019-06-11 Gilead Sciences, Inc. Tank-binding kinase inhibitor compounds
US10941178B2 (en) 2017-03-17 2021-03-09 Gilead Sciences, Inc. Method of purifying an antibody

Also Published As

Publication number Publication date
AU2015271837B2 (en) 2018-06-14
NZ726317A (en) 2018-05-25
US20190016717A1 (en) 2019-01-17
IL248888A0 (en) 2017-01-31
KR20180131640A (ko) 2018-12-10
AU2018208766A1 (en) 2018-08-16
ES2961577T3 (es) 2024-03-12
KR101926245B1 (ko) 2018-12-06
EA201692203A1 (ru) 2017-06-30
KR20170005876A (ko) 2017-01-16
TW201613916A (en) 2016-04-16
MX2016015862A (es) 2017-03-27
EP3152210C0 (en) 2023-07-05
JP6378785B2 (ja) 2018-08-22
EP3152210B1 (en) 2023-07-05
CN106459044A (zh) 2017-02-22
AU2015271837A1 (en) 2016-12-01
CA2951126A1 (en) 2015-12-10
JP2018150358A (ja) 2018-09-27
SG11201609570SA (en) 2016-12-29
EP3152210A1 (en) 2017-04-12
US10072001B2 (en) 2018-09-11
WO2015187684A1 (en) 2015-12-10
JP2017516814A (ja) 2017-06-22
MA40058A (fr) 2015-12-10
US10259811B2 (en) 2019-04-16
EA031757B1 (ru) 2019-02-28
BR112016028288A2 (pt) 2017-08-22
HK1231475A1 (zh) 2017-12-22
US20150344473A1 (en) 2015-12-03

Similar Documents

Publication Publication Date Title
AR100702A1 (es) Compuestos inhibidores de quinasa de unión tank
AR110405A1 (es) Compuestos
AR107912A1 (es) Inhibidores de ret
AR103252A1 (es) Compuestos de quinazolina
AR101189A1 (es) Heterociclos nitrogenados antiproliferativos y sus métodos de uso
AR099955A1 (es) Compuestos de heteroarilo o arilo bicíclicos fusionados
AR104176A1 (es) Inhibidores de ido (indolamina-2,3-dioxigenasa)
AR100058A1 (es) DERIVADOS DE PIRIMIDIN-PIRAZINAS FUSIONADAS MODULADORES DE RORg
AR111407A1 (es) Compuestos inhibidores de ask1 y usos de los mismos
AR101600A1 (es) COMPUESTOS DE SPIRO[3H-INDOL-3,2-PIRROLIDIN]-2(1H)-ONA Y DERIVADOS COMO INHIBIDORES DE MDM2-p53
AR094300A1 (es) Derivados de quinolonas
AR107061A1 (es) Heteroarilhidroxipirimidinonas como agonistas del receptor de apj
AR106301A1 (es) Composiciones de pirrolpirimidina como inhibidores de quinasas
AR092349A1 (es) Imidazotriazincarbonitrilos utiles como inhibidores de quinasa
AR097082A1 (es) Compuestos terapéuticamente activos y sus métodos de uso
AR103232A1 (es) ANTAGONISTAS DE TGFbR
AR107054A1 (es) DERIVADOS DE ISOINDOL Y COMPOSICIONES FARMACÉUTICAS QUE LOS COMPRENDEN PARA EL TRATAMIENTO DE ENFERMEDADES MEDIADAS POR RORg Y RORgt
AR107955A1 (es) Derivados de piridino- / pirimidino-piridina, con actividad herbicida
AR112086A1 (es) Compuestos heteroaromáticos como inhibidores de vanina
AR100448A1 (es) 5-(hetero)aril-piridazinonas y su uso como herbicida
AR107953A1 (es) Derivados de piridino- / pirimidino-piridina, con actividad herbicida
AR102773A1 (es) Derivados de pirido benzodiazepina sustituidos y su utilización
AR100706A1 (es) Derivados de naftiridinadiona
AR116392A1 (es) Compuestos de fenoxi-piridil-pirimidina y métodos de uso
AR099690A1 (es) Ureas asimétricas p-sustituidas como moduladoras de la actividad de ghrelina

Legal Events

Date Code Title Description
FB Suspension of granting procedure