AR120481A1 - Compuestos útiles como inhibidores de la proteína helios - Google Patents

Compuestos útiles como inhibidores de la proteína helios

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Publication number
AR120481A1
AR120481A1 ARP200103178A ARP200103178A AR120481A1 AR 120481 A1 AR120481 A1 AR 120481A1 AR P200103178 A ARP200103178 A AR P200103178A AR P200103178 A ARP200103178 A AR P200103178A AR 120481 A1 AR120481 A1 AR 120481A1
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Argentina
Prior art keywords
alkyl
phenyl
fluoroalkyl
independently
alkoxy
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ARP200103178A
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English (en)
Inventor
Andrew P Degnan
Godwin Kwame Kumi
Audris Huang
James Aaron Balog
Ashok Vinayak Purandare
Weifang Shan
Li Guo
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Bristol Myers Squibb Co
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Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of AR120481A1 publication Critical patent/AR120481A1/es

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    • 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
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/4709—Non-condensed quinolines and 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
    • A61K31/435—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
    • A61K31/495—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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines 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
    • A61K31/495—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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and 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
    • 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
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 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
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • 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
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • 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
    • C07D498/12—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 three hetero rings
    • C07D498/18—Bridged systems

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

Abstract

Reivindicación 1: Un compuesto de la fórmula (1) o una sal del mismo, en donde: Z es CR⁶R⁶ o C=O; el anillo A es: un compuesto seleccionado del grupo de fórmulas (2); R¹ es -(CRᶻRᶻ)₁₋₂NR¹ᵃR¹ᵇ; R¹ᵃ es hidrógeno, alquilo C₁₋₆, fluoroalquilo C₁₋₄, cianoalquilo C₁₋₃, hidroxialquilo C₁₋₆, -(CH₂)₁₋₃O(alquilo C₁₋₃), -(CH₂)₁₋₃S(O)₂(alquilo C₁₋₃), -(CH₂)₁₋₃C₍O₎O₍ₐₗqᵘⁱₗₒ C₁₋₃), -(CH₂)₁₋₃NRˣRˣ, -(CH₂)₁₋₃C₍O₎NRˣRˣ, -(CH₂)₁₋₃NRˣC(O)(alquilo C₁₋₃), -C(O)(alquilo C₁₋₃), -CH(fenil)(hidroxialquilo C₁₋₂), -CRˣRˣCRˣ(fenil)₂, R¹ᶜ, -(CRˣRˣ)₁₋₃R¹ᶜ, -(CRˣRˣ)₁₋₃OR¹ᶜ, o -C(O)R¹ᶜ; R¹ᵇ es hidrógeno, alquilo C₁₋₃, o -CH₂(fenil); o R¹ᵃ y R¹ᵇ junto con el átomo de nitrógeno al que están unidos, se unen para formar un grupo cíclico seleccionado de azaspiro[2.5]octanilo, azepanilo, azetidinilo, azocanilo, diazepanilo, dioxidotiomorfolinilo, isoindolinilo, morfolinilo, octahidrociclopenta[b]pirrolilo, octahidropirrolo[3,4-c]pirrolilo, oxaazabiciclo[2.2.1]heptanilo, piperazinonilo, piperazinilo, piperidinonilo, piperidinilo, pirrolidinilo, pirrolidinonilo, y tetrahidroisoquinolinilo, cada uno sustituido por cero a 1 R¹ᵈ y cero a 2 R¹ᵉ; R¹ᶜ es cicloalquilo C₃₋₇, fenilo, oxetanilo, azetidinilo, furanilo, piranilo, pirrolilo, pirrolidinilo, pirrolidinonilo, pirazolilo, imidazolilo, indazolilo, tiazolilo, piperidinilo, piridinilo, tetrahidrofuranilo, tetrahidropiranilo, morfolinilo, dioxotetrahidrotiopiranilo, dioxidotetrahidrotiofenilo, benzo[d]tiazolilo, naftalenilo, quinolinilo, o quinoxalinilo, cada uno sustituido por cero a 2 sustituyentes independientemente seleccionados F, Cl, -CN, -OH, alquilo C₁₋₃, fluoroalquilo C₁₋₃, hidroxialquilo C₁₋₃, alcoxi C₁₋₃, fluoroalcoxi C₁₋₃, -C(O)O(alquilo C₁₋₃), -NRʸRʸ, -S(O)₂(alquilo C₁₋₃), -S(O)₂NRˣRˣ, -CH₂(fenilo), -NO₂, cicloalquilo C₃₋₆, imidazolilo, y fenilo; R¹ᵈ es alquilo C₁₋₄, fluoroalquilo C₁₋₂, alcoxi C₁₋₃, -NRʸRʸ, -NRˣC(O)(alquilo C₁₋₃), -C(O)(alquilo C₁₋₃), -C(O)NRʸRʸ, -CH₂(fenilo), -CH₂(metilpirrolidinilo), -CH₂(benzo[d][1,3]dioxolilo), -CH(fenilo)₂, -C(O)(tetrahidrofuranilo), -C(O)(furanilo), -S(O)₂(metilfenilo), fenilo, metilfenilo, aminofenilo, piperidinilo, pirazinilo, piridinilo, pirimidinilo, pirrolidinilo, o dihidrobenzo[d]imidazolonilo; R¹ᵉ es CH₃; cada R² es independientemente halógeno, -CN, alquilo C₁₋₃, fluoroalquilo C₁₋₃, alcoxi C₁₋₃, o fluoroalcoxi C₁₋₃; NR₂ (R = H, alquilo C₁₋₃), opcionalmente sustituido fenilo, opcionalmente sustituido heteroarilo; R³ es R¹ᵃ; cada R⁴ es independientemente halógeno, -CN, alquilo C₁₋₃, fluoroalquilo C₁₋₃, alcoxi C₁₋₃, o fluoroalcoxi C₁₋₃; cada R⁴ es independientemente halógeno, -CN, -OH, alquilo C₁₋₃, fluoroalquilo C₁₋₃, alcoxi C₁₋₃, fluoroalcoxi C₁₋₃, o -NRʸRʸ; R⁵ es hidrógeno, F, o alquilo C₁₋₃; cada R⁶ es independientemente hidrógeno o alquilo C₁₋₃; cada Rˣ es independientemente H o -CH₃; cada Rʸ es independientemente H o alquilo C₁₋₄; cada Rᶻ es independientemente H o -CH₃; o dos Rᶻ unido al mismo átomo de carbono, forman un anillo carbocíclico de 3 a 6 miembros o un anillo heterocíclico de 3 a 6 miembros; m es cero, 1, ó 2; y n es cero, 1, 2, ó 3.
ARP200103178A 2019-11-19 2020-11-18 Compuestos útiles como inhibidores de la proteína helios AR120481A1 (es)

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EP (1) EP4061812A1 (es)
JP (1) JP2023503052A (es)
KR (1) KR20220103753A (es)
CN (1) CN114728950B (es)
AR (1) AR120481A1 (es)
AU (1) AU2020387392A1 (es)
BR (1) BR112022009514A2 (es)
CA (1) CA3158976A1 (es)
IL (1) IL293027A (es)
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