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MX2020001531A - Nuevos compuestos hetorociclicos como inhibidores de cdk8/19. - Google Patents

Nuevos compuestos hetorociclicos como inhibidores de cdk8/19.

Info

Publication number
MX2020001531A
MX2020001531A MX2020001531A MX2020001531A MX2020001531A MX 2020001531 A MX2020001531 A MX 2020001531A MX 2020001531 A MX2020001531 A MX 2020001531A MX 2020001531 A MX2020001531 A MX 2020001531A MX 2020001531 A MX2020001531 A MX 2020001531A
Authority
MX
Mexico
Prior art keywords
compounds
hetorocyclic
cdk8
inhibitors
new
Prior art date
Application number
MX2020001531A
Other languages
English (en)
Inventor
Aleksandrovich Aleshunin Pavel
Vladimirovna Kozhemyakina Natalia
Valentinovich MOROZOV Dmitry
Andreevich IAKOVLEV Pavel
Leonidovich MINDICH Aleksei
Leonidovna Gorbunova Svetlana
Vladimirovna Popkova Aleksandra
Evgenievich Shekhautsou Artsiom
Ivanovich Alafinov Andrei
Aleksandrovich EVDOKIMOV Anton
Vadimovich Zavialov Kirill
Andreevna KASATKINA Mariia
Sergeevna Kushakova Anna
Aleksandrovna MAKSIMENKO Elena
Sergeevna Mishina Mariia
Vladimirovich Rekharsky Mikhail
Jur'evna CHESTNOVA Anna
Original Assignee
Biocad Joint Stock Co
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
Priority claimed from RU2017128123A external-priority patent/RU2017128123A/ru
Priority claimed from RU2018108178A external-priority patent/RU2739489C2/ru
Application filed by Biocad Joint Stock Co filed Critical Biocad Joint Stock Co
Publication of MX2020001531A publication Critical patent/MX2020001531A/es

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    • 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
    • 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
    • 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
    • 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
    • A61K31/41—Heterocyclic 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/4353—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
    • A61K31/4375—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 six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K31/535—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
    • 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
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D403/12—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 chain containing hetero atoms as chain links
    • 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
    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La presente invención hace referencia a los nuevos compuestos de la fórmula I: (ver Fórmula) o de su sal farmacéuticamente aceptada o su estereoisómero, Donde X1 representa N, C, CH; X2, X3, X4 cada uno independientemente representa C(H)m, NH, N, CR13, CHR13; L1, L2 cada uno independientemente representa el enlace químico, -C(R6b)2-, -O-, -C(O)-, -C(O)-O-, -NH-, -C(=NR19)-; n, k cada uno es seleccionado independientemente entre 0, 1; m representa 0, 1, 2; R1, R3, R13 cada uno independientemente representa H, Hal, ciano, alquilo C1-C6, NH2; R2, R4 se seleccionan cada uno independientemente del grupo que consiste de: (ver Fórmula) -NR11R12; alquilo C1-C6, sustituido o no sustituido con uno o más sustituyentes R14; X5, X6, X7 cada uno independientemente representa C, CH, N; L3, L4 cada uno independientemente representa el enlace químico, -C(O)-, -O-, -CH2-, -NH-, -C(O)-NR7a -, -C (=NH)-; p = 0, 1, 2, 3, 4; R5 representa H; Hal; ciano; alquilo C1-C6; alquiloxi C1-C6 alquiloxi C1-C6 alquilo C1-C6; NR15R16; arilo, sustituido o no sustituido con uno o varios sustituyentes seleccionados del grupo que consiste de Hal, alquilo C1-C6, alquiloxi C1-C6, NR15R16; heterociclilo de 5-6 componentes con 1-2 heteroátomos seleccionados entre N y/u O, sin sustituir o sustituido con uno o más sustituyentes seleccionados del grupo que consiste en Hal, alquilo C1-C6, alquiloxi C1-C6 6, NR15R16; R6, R6a, R6b cada uno independientemente representa H, Hal, hidroxi, alquilo C1-C6, alquiloxi C1-C6; R7, R7a cada uno independientemente representa H, alquilo C1-C6; R8, R9 cada uno independientemente representa H, alquilo C1-C6, -C(O)-NR21R22, -CN, -C(O)-OR20; o R8 y R9 junto con un átomo de carbono al cual están unidos, forman un anillo heterocíclico de 5-6 componentes con 1-2 heteroátomos, seleccionados de oxígeno y/o nitrógeno, donde el anillo heterocíclico formado con R8 y R9 puede ser sustituido o no sustituido con 1 o 2 sustituyentes seleccionado del grupo oxo, alquilo C1-C6; R10 cada uno es independientemente seleccionado del grupo constituido por H, Hal, alquilo C1-C6, hidroxi, ciano, alquiloxi C1-C6, alquiloxi C1-C6 alquilo C1-C6, -NR23R24; heterociclo de 5-6 componentes con 1-2 heteroátomos seleccionados entre N, O y/o S, sustituido o no sustituido por uno o varios alquilos C1-C6; heteroarilo de 5-6 componentes con 1-2 heteroátomos seleccionados entre N, O y/o S, sustituido o no sustituido con uno o varios alquilos C1-C6; alquilo -S(O)2-C1-C6; R11, R12 cada uno independientemente representa H; alquilo C1-C6, sustituido o no sustituido por hidroxi, cicloalquilo C3-C6, -NR23aR24a; alcoxi C1-C6 alquilo C1-C6; cicloalquilo C3-C6; R14 cada uno independientemente representa Hal, -C(O)NR17R18, alcoxi C1-C6; R15, R16, R19, R20, R21, R22, R23, R24, R23a, R24a cada uno independientemente representa H, alquilo C1-C6; R17, R18 cada uno independientemente representa H, alquilo C1-C6; arilo, sustituido o no sustituido por uno o varios sustituyentes seleccionados del grupo constituido por Hal, alquilo C1-C6, alcoxi C1-C6; (ver Símbolo) cada una representa independientemente un enlace sencillo o un enlace doble; Hal representa cloro, bromo, yodo, flúor; y que tienen las propiedades de un inhibidor de CDK8/19, características de una composición farmacéutica que contiene estos compuestos y su uso como fármacos para el tratamiento de enfermedades o trastornos.
MX2020001531A 2017-08-07 2018-07-30 Nuevos compuestos hetorociclicos como inhibidores de cdk8/19. MX2020001531A (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
RU2017128123A RU2017128123A (ru) 2017-08-07 2017-08-07 Новые гетероциклические соединения как ингибиторы CDK8/19
RU2018108178A RU2739489C2 (ru) 2018-03-06 2018-03-06 Новые гетероциклические соединения как ингибиторы CDK8/19
PCT/RU2018/050089 WO2019031990A1 (ru) 2017-08-07 2018-07-30 Новые гетероциклические соединения как ингибиторы cdk8/19

Publications (1)

Publication Number Publication Date
MX2020001531A true MX2020001531A (es) 2020-03-20

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MX2020001531A MX2020001531A (es) 2017-08-07 2018-07-30 Nuevos compuestos hetorociclicos como inhibidores de cdk8/19.

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EP (1) EP3666770A4 (es)
JP (1) JP7365332B2 (es)
KR (1) KR102700664B1 (es)
CN (2) CN120794975A (es)
AU (1) AU2018312836B2 (es)
BR (1) BR112020002674A2 (es)
CA (1) CA3075477A1 (es)
CO (1) CO2020001326A2 (es)
MX (1) MX2020001531A (es)
UY (1) UY37837A (es)
WO (1) WO2019031990A1 (es)

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Publication number Publication date
UY37837A (es) 2019-02-28
JP7365332B2 (ja) 2023-10-19
WO2019031990A1 (ru) 2019-02-14
KR20200051626A (ko) 2020-05-13
KR102700664B1 (ko) 2024-08-29
AU2018312836A1 (en) 2020-03-26
BR112020002674A2 (pt) 2020-07-28
JP2020530020A (ja) 2020-10-15
EP3666770A1 (en) 2020-06-17
CO2020001326A2 (es) 2020-04-01
CA3075477A1 (en) 2019-02-14
CN120794975A (zh) 2025-10-17
AU2018312836B2 (en) 2022-12-08
CN111670183A (zh) 2020-09-15
EP3666770A4 (en) 2021-04-07

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