AR097894A1 - Therapeutic inhibitors of cdk8 or use thereof - Google Patents

Therapeutic inhibitors of cdk8 or use thereof

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Publication number
AR097894A1
AR097894A1 ARP140103670A ARP140103670A AR097894A1 AR 097894 A1 AR097894 A1 AR 097894A1 AR P140103670 A ARP140103670 A AR P140103670A AR P140103670 A ARP140103670 A AR P140103670A AR 097894 A1 AR097894 A1 AR 097894A1
Authority
AR
Argentina
Prior art keywords
rv
ra
c2
c1
alkyl
Prior art date
Application number
ARP140103670A
Other languages
Spanish (es)
Original Assignee
F Hoffmann-La Roche Ag
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.)
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Publication date
Priority to US201361886547P priority Critical
Application filed by F Hoffmann-La Roche Ag filed Critical F Hoffmann-La Roche Ag
Publication of AR097894A1 publication Critical patent/AR097894A1/en

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Classifications

    • 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 C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • 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
    • C07D403/04Heterocyclic 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

Abstract

Los compuestos son útiles como inhibidores de CDK8. The compounds are useful as inhibitors of CDK8. También se incluyen composiciones farmacéuticamente aceptables que comprenden los compuestos de la presente y métodos para usar dichas composiciones en el tratamiento de varios trastornos. Pharmaceutically acceptable compositions comprising the compounds of the present and methods for using such compositions in the treatment of various disorders are also included. Reivindicación 1: Un compuesto de fórmula (1), o una sal del mismo, donde: R¹ se selecciona entre: los restos de fórmula (2) y (3); CLAIMS 1. A compound of formula (1) or a salt thereof, wherein: R¹ is selected from the moieties of formula (2) and (3); y donde R¹ está opcionalmente sustituido opcionalmente con 1, 2 ó 3 grupos Rˣ; and where R¹ is optionally optionally substituted with 1, 2 or 3 groups R; R² y R³ son independientemente H, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂; R² and R³ are independently H, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl; carbociclilo, arilo, heteroarilo, heterociclilo, halo, -ORᵃ, -SRᵃ, -N(Rᵃ)₂, -CN, -NO₂, -C(O)Rᵃ, -CO₂Rᵃ, -C(O)N(Rᵃ)₂, -C(O)SRᵃ, -C(O)C(O)Rᵃ, -C(O)CH₂C(O)Rᵃ, -C(S)N(Rᵃ)₂, -C(S)ORᵃ, -S(O)Rᵃ, -SO₂Rᵃ, -SO₂N(Rᵃ)₂, -N(Rᵃ)C(O)Rᵃ, -N(Rᵃ)C(O)N(Rᵃ)₂, -N(Rᵃ)SO₂Rᵃ, -N(Rᵃ)SO₂N(Rᵃ)₂, -N(Rᵃ)N(Rᵃ)₂, -N(Rᵃ)C(=N(Rᵃ))N(Rᵃ)₂, -C(=N)N(Rᵃ)₂, -C=NORᵃ, -C(=N(Rᵃ))N(Rᵃ)₂, -OC(O)Rᵃ, o -OC(O)N(Rᵃ)₂, donde cada alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂; carbocyclyl, aryl, heteroaryl, heterocyclyl, halo, -ORᵃ, -SRᵃ, -N (Rᵃ) ₂, -CN, -NO₂, -C (O) Rᵃ, -CO₂Rᵃ, -C (O) N (Rᵃ) ₂, -C (O) SRᵃ, -C (O) C (O) Rᵃ, -C (O) CH₂C (O) Rᵃ, -C (S) N (Rᵃ) ₂, -C (S) ORᵃ, -S ( O) Rᵃ, -SO₂Rᵃ, -SO₂N (Rᵃ) ₂, -N (Rᵃ) C (O) Rᵃ, -N (Rᵃ) C (O) N (Rᵃ) ₂, -N (Rᵃ) SO₂Rᵃ, -N ( Rᵃ) SO₂N (Rᵃ) ₂, -N (Rᵃ) N (Rᵃ) ₂, -N (Rᵃ) C (= N (Rᵃ)) N (Rᵃ) ₂, -C (= N) N (Rᵃ) ₂, -C = NORᵃ, -C (= N (Rᵃ)) N (Rᵃ) ₂, -OC (O) Rᵃ, or -OC (O) N (Rᵃ) ₂, where each alkyl C₁₋₁₂ alkenyl, C₂₋₁₂ alkynyl C₂₋₁₂; carbociclilo, arilo, heteroarilo, y heterociclilo de R² y R³ están independientemente sustituidos opcionalmente con uno o más grupos Rˣ; carbocyclyl, aryl, heteroaryl, and heterocyclyl R² and R³ are independently optionally substituted with one or more R groups; o R¹ y R² tomados junto con los átomos a los que están unidos forman un carbociclilo, heterociclilo, heteroarilo o arilo de 4, 5, 6, 7 u 8 miembros, donde dichos carbociclilo, heterociclilo, heteroarilo y arilo están opcionalmente sustituidos con uno o más grupos Rˣ; or R¹ and R² taken together with the atoms to which they are attached form a carbocyclyl, heterocyclyl, aryl or heteroaryl of 4, 5, 6, 7 or 8 members, wherein said carbocyclyl, heterocyclyl, heteroaryl and aryl are optionally substituted with one or more R groups; cada Rᵃ y Rᵇ son de independientemente H, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆; each Rᵃ and Rᵇ are independently H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl; carbociclilo, arilo, heteroarilo, o heterociclilo, donde cada alquilo C₁₋₆, alquenilo C₃₋₆, alquinilo C₃₋₆; carbocyclyl, aryl, heteroaryl, or heterocyclyl, where each alkyl C₁₋₆, alkenyl C₃₋₆ alkynyl C₃₋₆; carbociclilo, arilo, heteroarilo, y heterociclilo están independientemente sustituido opcionalmente con uno o más grupos Rˣ; carbocyclyl, aryl, heteroaryl, and heterocyclyl are optionally independently substituted with one or more groups R; o Rᵃ y Rᵇ se toman junto con el nitrógeno al que están unidos para formar un heterociclo de 3 - 6 miembros opcionalmente sustituido con oxo, halo, o alquilo C₁₋₆ opcionalmente sustituido con oxo o halo; or Rᵃ and Rᵇ are taken together with the nitrogen to which they are attached to form a heterocycle of 3 to 6 members optionally substituted by oxo, halo, or alkyl C₁₋₆ optionally substituted with oxo or halo; cada Rᵛ es independientemente hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆; Rᵛ each is independently hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl; carbociclilo, arilo, heteroarilo, o heterociclilo, donde cada alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆; carbocyclyl, aryl, heteroaryl, or heterocyclyl, where each alkyl C₁₋₆, alkenyl C₂₋₆ alkynyl C₂₋₆; carbociclilo, arilo, heteroarilo, y heterociclilo está opcionalmente sustituido con uno o más grupos seleccionados independientemente entre oxo, halo, amino, hidroxilo, y alquilo C₁₋₆ que está opcionalmente sustituido con uno o más grupos seleccionados independientemente entre oxo y halo; carbocyclyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or more groups independently selected from oxo, halo, amino, hydroxy, and C₁₋₆ alkyl which is optionally substituted with one or more groups independently selected from oxo and halo; o dos Rᵛ se toman junto con el nitrógeno a que están unidos para formar un heterociclilo de 3 - 6 miembros que está opcionalmente sustituido con uno o más grupos seleccionados entre oxo, halo y alquilo C₁₋₃ que está opcionalmente sustituido con uno o más grupos seleccionados independientemente entre oxo y halo; or two Rᵛ are taken together with the nitrogen to which they are attached to form a heterocyclyl 3 to 6 members which is optionally substituted with one or more groups selected from oxo, halo and C₁₋₃ alkyl is optionally substituted with one or more groups independently selected from oxo and halo; y cada Rˣ es independientemente oxo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆; and each R is independently oxo, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl; haloalquilo C₁₋₆, carbociclilo, arilo, heteroarilo, heterociclilo, -F, -Cl, -Br, -I, -NO₂, -N(Rᵛ)₂, -CN, -C(O)-N(Rᵛ)₂, -S(O)-N(Rᵛ)₂, -S(O)₂-N(Rᵛ)₂, -O-Rᵛ, -S-Rᵛ, -OC(O)-Rᵛ, -OC(O)-O-Rᵛ, -C(O)-Rᵛ, -C(O)-O-Rᵛ, -S(O)-Rᵛ, -S(O)₂-Rᵛ, -OC(O)-N(Rᵛ)₂, -N(Rᵛ)-C(O)-ORᵛ, -N(Rᵛ)-C(O)-N(Rᵛ)₂, -S(O)₂-N(Rᵛ)₂, -N(Rᵛ)-C(O)-Rᵛ, -N(Rᵛ)-S(O)-Rᵛ, -N(Rᵛ)-S(O)₂-Rᵛ, -N(Rᵛ)-S(O)-N(Rᵛ)₂, o -N(Rᵛ)-S(O)₂-N(Rᵛ)₂, donde cualquier alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆; C₁₋₆ haloalkyl, carbocyclyl, aryl, heteroaryl, heterocyclyl, -F, -Cl, -Br, -I, -NO₂, -N (Rᵛ) ₂, -CN, -C (O) -N (Rᵛ) ₂, -S (O) -N (Rᵛ) ₂, -S (O) ₂-N (Rᵛ) ₂, -O-Rᵛ, -S-Rᵛ, -OC (O) -Rᵛ, -OC (O) -O -Rᵛ, -C (O) -Rᵛ, -C (O) -O-Rᵛ, -S (O) -Rᵛ, -S (O) ₂-Rᵛ, -OC (O) -N (Rᵛ) ₂, -N (Rᵛ) -C (O) -ORᵛ, -N (Rᵛ) -C (O) -N (Rᵛ) ₂, -S (O) ₂-N (Rᵛ) ₂, -N (Rᵛ) -C (O) -Rᵛ, -N (Rᵛ) -S (O) -Rᵛ, -N (Rᵛ) -S (O) ₂-Rᵛ, -N (Rᵛ) -S (O) -N (Rᵛ) ₂, or -N (Rᵛ) -S (O) ₂-N (Rᵛ) ₂ where any C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl; haloalquilo C₁₋₆, carbociclilo, arilo, heteroarilo, y heterociclilo está opcionalmente sustituido independientemente con uno o más grupos seleccionados entre oxo, halo, -NO₂, -N(Rᵛ)₂, -CN, -C(O)-N(Rᵛ)₂, -S(O)-N(Rᵛ)₂, -S(O)₂-N(Rᵛ)₂, -O-Rᵛ, -S-Rᵛ, -OC(O)-Rᵛ, -C(O)-Rᵛ, -C(O)-O-Rᵛ, -S(O)-Rᵛ, -S(O)₂-Rᵛ, -C(O)-N(Rᵛ)₂, -S(O)₂-N(Rᵛ)₂, -N(Rᵛ)-C(O)-Rᵛ, -N(Rᵛ)-S(O)-Rᵛ -N(Rᵛ)-S(O)₂-Rᵛ y alquilo C₁₋₆ que está opcionalmente sustituido con uno o más grupos seleccionados independientemente entre oxo y halo; C₁₋₆ haloalkyl, carbocyclyl, aryl, heteroaryl, and heterocyclyl is optionally substituted independently with one or more groups selected from oxo, halo, -NO₂, -N (Rᵛ) ₂, -CN, -C (O) -N (Rᵛ ) ₂, -S (O) -N (Rᵛ) ₂, -S (O) ₂-N (Rᵛ) ₂, -O-Rᵛ, -S-Rᵛ, -OC (O) -Rᵛ, -C (O ) -Rᵛ, -C (O) -O-Rᵛ, -S (O) -Rᵛ, -S (O) ₂-Rᵛ, -C (O) -N (Rᵛ) ₂, -S (O) ₂- N (Rᵛ) ₂, -N (Rᵛ) -C (O) -Rᵛ, -N (Rᵛ) -S (O) -N -Rᵛ (Rᵛ) -S (O) ₂-C₁₋₆ alkyl Rᵛ and that It is optionally substituted with one or more groups independently selected from oxo and halo; y en el que cuando R² es F y R³ es hidrógeno, entonces Rˣ es distinto de metilo, etilo, trifluorometilo o 2-fluorofenilo. and wherein when R² is F and R³ is hydrogen, then R is other than methyl, ethyl, trifluoromethyl or 2-fluorophenyl.
ARP140103670A 2013-10-03 2014-10-02 Therapeutic inhibitors of cdk8 or use thereof AR097894A1 (en)

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US201361886547P true 2013-10-03 2013-10-03

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WO2019068613A1 (en) 2017-10-02 2019-04-11 Boehringer Ingelheim International Gmbh New [1,6]naphthyridine compounds and derivatives as cdk8/cdk19 inhibitors

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WO2015049325A1 (en) 2015-04-09

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