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AR127505A1 - Degradadores irak-4 y síntesis de los mismos - Google Patents

Degradadores irak-4 y síntesis de los mismos

Info

Publication number
AR127505A1
AR127505A1 ARP220102952A ARP220102952A AR127505A1 AR 127505 A1 AR127505 A1 AR 127505A1 AR P220102952 A ARP220102952 A AR P220102952A AR P220102952 A ARP220102952 A AR P220102952A AR 127505 A1 AR127505 A1 AR 127505A1
Authority
AR
Argentina
Prior art keywords
nitrogen
membered
sulfur
oxygen
saturated
Prior art date
Application number
ARP220102952A
Other languages
English (en)
Inventor
William Leong
Dharyl Charles Wilson
Original Assignee
Kymera Therapeutics 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 Kymera Therapeutics Inc filed Critical Kymera Therapeutics Inc
Publication of AR127505A1 publication Critical patent/AR127505A1/es

Links

Classifications

    • 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
    • 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
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged 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
    • A61K31/535—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
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Saccharide Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

Reivindicación 1: Una composición que comprende compuesto (I-1) o una sal del mismo farmacéuticamente aceptable, y uno o más compuestos con impureza que se seleccionan del grupo integrado por: los compuestos (I-2) a (I-9), o una sal del mismo farmacéuticamente aceptable. Reivindicación 27: Un proceso para preparar un compuesto de fórmula (1) o una sal del mismo farmacéuticamente aceptable, donde: X es una porción bivalente que se selecciona de un enlace covalente, -CH₂-, -C(O)-, -C(S)-, o un resto de fórmula (4); R¹, R², R³, R⁴, y R⁵, independientemente, se seleccionan de hidrógeno, deuterio, RA, halógeno, -CN, -NO₂, -OR, -SR, -NR₂, -SO₂R, -SO₂NR₂, -S(O)R, -CFR₂, -CF₂R, -CF₃, -CR₂OR, -CR₂(NR₂), -C(O)R, -C(O)OR, -C(O)NR₂, -C(S)NR₂, -C(O)NROR, -OC(O)R, -OC(O)NR₂, -NRC(O)OR, -NRC(O)R, -NRC(O)NR₂, -NRSO₂R, -N⁺(O⁻)R₂, -OP(O)R₂, -OP(O)(OR)₂, -OP(O)(OR)NR₂, -OP(O)(NR₂)₂, -P(O)R₂, -SiR₃, -Si(OR)R₂, o un resto de fórmula (5); cada R, independientemente, es hidrógeno, o un grupo opcionalmente sustituido seleccionado de C₁₋₆ alifático, fenilo, un heterocíclico de 3 - 7 miembros saturado o parcialmente insaturado que tiene 1 - 2 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, y un anillo heteroarilo de 5 - 6 que tiene 1 - 4 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, o: dos grupos R en el mismo carbono o nitrógeno se toman opcionalmente juntos con sus átomos intervinientes para formar un anillo carbocíclico o heterocíclico de 4 - 11 miembros saturado o parcialmente insaturado monocíclico, bicíclico, bicíclico puenteado, o espirocíclico que tiene 1 - 3 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, o un anillo heteroarilo de 5 - 9 miembros que tiene 1 - 4 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre; cada RA, independientemente, es un grupo opcionalmente sustituido seleccionado de C₁₋₆ alifático, fenilo, un anillo heterocíclico saturado o parcialmente insaturado de 4 - 7 miembros que tiene 1 - 2 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, y un anillo heteroarilo de 5 - 6 que tiene 1 - 4 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre; a, b, c, d, y e, independientemente, se seleccionan de 0, 1, 2, 3, o 4; R⁶ es hidrógeno o C₁₋₆ alifático; Anillo A, Anillo B, y Anillo E, independientemente, se seleccionan de fenilo, naftilo, un anillo carbocíclico o heterocíclico de 4 - 11 miembros saturado o parcialmente insaturado monocíclico, bicíclico, bicíclico puenteado, o espirocíclico que tiene 1 - 3 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, o un anillo heteroarilo de 5 - 10 miembros monocíclico o bicíclico que tiene 1 - 4 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre; Anillo C es un anillo carbocíclico o heterocíclico de 4 - 6 miembros saturado o parcialmente insaturado que tiene 1 - 2 heteroátomos seleccionados de nitrógeno, oxígeno, y azufre; Anillo D es un anillo heterocíclico de 4 - 6 miembros saturado o parcialmente insaturado que tiene, además del nitrógeno presente, 0 - 2 heteroátomos seleccionados de nitrógeno, oxígeno, y azufre; L es un enlace covalente o uno bivalente, cadena de hidrocarburos C₁₋₁₀ saturada o insaturada, recta o ramificada, donde 0 - 6 unidades metileno de L se reemplazan independientemente por -CDH-, -CD₂-, -CRF-, -CF₂-, -Cy-, -O-, -NR-, -SiR₂-, -Si(OH)R-, -Si(OH)₂-, -P(O)OR-, -P(O)R-, -P(O)NR₂-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -SO₂-, -NRSO₂-, -SO₂NR-, -NRC(O)-, -C(O)NR-, -OC(O)NR-, -NRC(O)O-, o un resto del grupo de fórmulas (6); cada -Cy-, independientemente, es un anillo bivalente opcionalmente sustituido seleccionado de fenilenilo, un arilenilo bicíclico de 8 - 10 miembros, un carbociclilenilo de 4 - 7 miembros saturado o parcialmente insaturado, un espiro carbociclilenilo de 4 - 12 miembros saturado o parcialmente insaturado, un carbociclilenilo bicíclico de 8 - 10 miembros saturado o parcialmente insaturado, un heterociclilenilo de 4 - 7 miembros saturado o parcialmente insaturado que tiene 1 - 2 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, un espiro heterociclilenilo de 4 - 12 miembros saturado o parcialmente insaturado que tiene 1 - 2 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, un heterociclilenilo bicíclico de 8 - 10 miembros saturado o parcialmente insaturado que tiene 1 - 2 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, un heteroarilenilo de 5 - 6 miembros que tiene 1 - 4 heteroátomos independientemente seleccionados de nitrógeno, oxígeno, y azufre, o un heteroarilenilo bicíclico de 8 - 10 miembros que tiene 1 - 5 heteroátomos independientemente seleccionados entre nitrógeno, oxígeno, o azufre; y r es 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, o 10, que comprende tratar un compuesto de fórmula (2) o sal farmacéuticamente aceptable del mismo, donde: X¹ es un grupo saliente adecuado, con un compuesto de fórmula (3) bajo condiciones adecuadas para formar el compuesto de fórmula (1) o una sal del mismo farmacéuticamente aceptable.
ARP220102952A 2021-10-29 2022-10-28 Degradadores irak-4 y síntesis de los mismos AR127505A1 (es)

Applications Claiming Priority (1)

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US202163263274P 2021-10-29 2021-10-29

Publications (1)

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Country Status (12)

Country Link
US (2) US12187744B2 (es)
EP (1) EP4422635A4 (es)
JP (1) JP2024540080A (es)
KR (1) KR20240110592A (es)
CN (1) CN118302168A (es)
AR (1) AR127505A1 (es)
AU (1) AU2022378630A1 (es)
CA (1) CA3236265A1 (es)
IL (1) IL312397A (es)
MX (1) MX2024005138A (es)
TW (1) TW202334165A (es)
WO (1) WO2023076556A1 (es)

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IL315310A (en) 2017-12-26 2024-10-01 Kymera Therapeutics Inc Irak degraders and uses thereof
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CN116867758A (zh) 2020-12-30 2023-10-10 凯麦拉医疗公司 Irak降解剂和其用途
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