AR109650A1 - Compuestos de heteroarilcarboxamida como inhibidores de ripk2 - Google Patents

Compuestos de heteroarilcarboxamida como inhibidores de ripk2

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Publication number
AR109650A1
AR109650A1 ARP170102539A ARP170102539A AR109650A1 AR 109650 A1 AR109650 A1 AR 109650A1 AR P170102539 A ARP170102539 A AR P170102539A AR P170102539 A ARP170102539 A AR P170102539A AR 109650 A1 AR109650 A1 AR 109650A1
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Argentina
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3alkyl
6alkyl
optionally substituted
membered
compounds
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ARP170102539A
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English (en)
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Zhonghua Zhang
Maolin Yu
Craig Andrew Miller
Pingrong Liu
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Boehringer Ingelheim Int
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Publication of AR109650A1 publication Critical patent/AR109650A1/es

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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • 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
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    • 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
    • A61K31/425—Thiazoles
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    • 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
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    • 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
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    • 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
    • A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring 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
    • C07D401/02—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
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    • 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
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    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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

Abstract

También composiciones farmacéuticas que comprenden estos compuestos, métodos para usar estos compuestos en el tratamiento de varias enfermedades y trastornos, procesos para preparar estos compuestos e intermediarios útiles en estos procesos. Reivindicación 1: Un compuesto caracterizado por la fórmula (1), o sales de aquel aceptables desde el punto de vista farmacéutico, en donde X es N e Y es CH; o X es CH e Y es N; HET es un anillo de heteroarilo de 5 miembros que contiene de 1 a 3 heteroátomos seleccionados de nitrógeno y azufre, en donde cada anillo de heteroarilo se sustituye opcionalmente con 1 a 2 grupos de sustituyentes seleccionados independientemente de R³ y R⁴; o HET es un anillo de heteroarilo de 5 miembros que contiene de 1 a 3 heteroátomos seleccionados de nitrógeno y azufre, en donde cada anillo de heteroarilo se sustituye con 2 grupos de sustituyentes seleccionados de Rᵃ y Rᵇ, en donde Rᵃ y Rᵇ, junto con los átomos a los que están unidos, forman un anillo heterocíclico o de heteroarilo de 5 - 6 miembros que puede ser opcionalmente sustituido con 1 a 2 sustituyentes seleccionados de R³ y R⁴; R¹ es hidrógeno o F; R² es C₁₋₃alquilo o Cl; R³ y R⁴ se seleccionan cada uno independientemente de: (a) -H, (b) -OR⁵, (c) -O-C₁₋₆alquil-O-C₁₋₃alquilo (d) -O-C₃₋₆cicloalquilo, (e) -C(O)R⁵, (f) C₁₋₆alquilo opcionalmente sustituido con 1 a 3 -OH, flúor, heterociclilo opcionalmente sustituido con oxo, C₃₋₆cicloalquilo, -CO₂R⁵, -O-C₁₋₆alquilo, arilo, -N(R⁵)(R⁶) o -C(O)N(R⁵)(R⁶), (g) C₃₋₆cicloalquilo opcionalmente sustituido con 1 a 3 -OH, 1 a 3 flúor, C₁₋₆alquilo, -OC₁₋₆alquilo, C₁₋₆alquil-OC₁₋₆alquilo, C₁₋₆alquilo-OH, CF₃, -OC₃₋₆cicloalquilo, -CO₂H, -CO₂R⁵, C₃₋₆cicloalquilo, heteroarilo de 5 - 6 miembros, C₃₋₆heterociclilo, N(R⁵)(R⁶) o -C(O)N(R⁵)(R⁶), (h) -CO₂R⁵, (i) -C(O)N(R⁵)(R⁶), (j) -S(O)₂N(R⁵)(R⁶), (k) -S(O)ₙ-R⁵, (l) un grupo heteroarilo de 5 - 6 miembros opcionalmente sustituido con 1 a 3 grupos seleccionados de C₁₋₆alquilo, C₃₋₆cicloalquilo, halógeno, -CF₃, -OH, -(CH₂)ₙCO₂R⁵, -C(O)N(R⁵)(R⁶), -N(R⁵)(R⁶), -NH-SO₂C₁₋₆alquilo, C₁₋₆alcoxilo, C₁₋₆alquil-O-C₁₋₃alquilo, C₁₋₆alquilhidroxilo, C₁₋₃alquil-CN, oxo, fenilo opcionalmente sustituido con halógeno y -S(O)ₙC₁₋₆alquilo, (m) grupo heterociclilo monocíclico, bicíclico o espirocíclico de 4 - 10 miembros que contiene N, S u O, en donde cada heterociclo es opcionalmente sustituido con 1 - 3 sustituyentes seleccionados de anillo heterocíclico de 3 - 6 miembros, halógeno, -C₁₋₃alquilo, -C₁₋₃alquil-O-C₁₋₃alquilo y -C₁₋₃alquil-C(O)N(R⁵)(R⁶), (n) arilo, (o) -N(R⁵)(R⁶); R⁵ y R⁶ se seleccionan cada uno independientemente de -H, heterociclilo de 4 - 6 miembros, -C(O)-C₁₋₃alquil-C(O)-C₁₋₃cicloalquilo y -C₁₋₆alquilo, en donde cada R⁵ y R⁶ se sustituye independientemente, de manera opcional, con -OH, C₃₋₆cicloalquilo, -C₁₋₃alquilo, -O-C₁₋₃alquilo, -NH-C₁₋₃alquilo o -N-(C₁₋₃alquilo)₂; o R⁵ y R⁶, junto con el átomo de nitrógeno al que están unidos, forman un anillo heterocíclico de 4 - 6 miembros opcionalmente sustituido con metilo; y n es 0, 1 ó 2.
ARP170102539A 2016-09-15 2017-09-14 Compuestos de heteroarilcarboxamida como inhibidores de ripk2 AR109650A1 (es)

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