AR045761A1 - Derivados de 2-piridona como inhibidores de elastasa de neutrofilos - Google Patents

Derivados de 2-piridona como inhibidores de elastasa de neutrofilos

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Publication number
AR045761A1
AR045761A1 ARP040103355A ARP040103355A AR045761A1 AR 045761 A1 AR045761 A1 AR 045761A1 AR P040103355 A ARP040103355 A AR P040103355A AR P040103355 A ARP040103355 A AR P040103355A AR 045761 A1 AR045761 A1 AR 045761A1
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Argentina
Prior art keywords
alkyl
independently selected
alkoxy
optionally further
further substituted
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ARP040103355A
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Marjana Andersson
Peter Hansen
Hans Lonn
Petter Sjolin
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Astrazeneca Ab
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Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Publication of AR045761A1 publication Critical patent/AR045761A1/es

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Abstract

Procesos para su preparación, composiciones que los contienen y su uso en terapia. Reivindicación 1:Un compuesto caracterizado porque responde a la fórmula (1), en donde: Y representa CR3 o N; R1 representa H o (C1-6) alquilo; R2 representa fenilo o un anillo heteroaromático de cinco o seis miembros que contiene 1 a 4 heteroátomos seleccionados en forma independiente entre O, S y N; estando dicho anillo aromático opcionalmente sustituido por 1 a 3 sustituyente seleccionados en forma independiente entre OH, halógeno, (C1-6)alquilo, (C1-6)alcoxi, NR58COR50, COOR51, COR52, CONR53R54 y NR47R48; estando dicho alquilo opcionalmente sustituido adicionalmente por OH, (C1-6)alcoxi, CN o CO2R49; R47 y R48 en forma independiente representa, H, (C1-6)alquilo o (C2-6)alcanoilo; R3 representa H o F; G1 representa fenilo o un anillo heteroaromático de cinco o seis miembros que contiene entre 1 y 3 heteroátomos seleccionados en forma independiente entre O, S y N; R5 representa H, halógeno, (C1-6)alquilo, CN, (C1-6)alcoxi, NO2, NR14R15, (C1-3)alquilo sustituido por uno o más átomos de F o (C1-3)alcoxi sustituido por uno o más átomos de F; R14 y R15 en forma independiente representan H o (C1-3)alquilo; estando dicho alquilo opcionalmente sustituido adicionalmente por uno o más átomos de F; n representa un entero 1, 2 ó 3 y cuando n representa 2 ó 3, cada grupo R5 se selecciona en forma independiente; R4 representa H o (C1-6)alquilo; estando dicho alquilo opcionalmente sustituido adicionalmente por OH o (C1-6)alcoxi; o R4 y L están unidos de forma tal que el grupo -R4L representa un anillo azacíclico de 5 a 7 miembros que incorpora opcionalmente un heteroátomo adicional seleccionado entre O, S y NR16; L representa un enlace, O, S(O)p, NR29 o (C1-6)alquilo; donde dicho alquilo incorpora opcionalmente un heteroátomo seleccionado entre O, S y NR16; y estando dicho alquilo opcionalmente sustituido adicionalmente por OH o OMe; G2 representa un sistema de anillo monocíclico seleccionado entre: i) fenilo o fenoxi; ii) un anillo heteroaromático de 5 ó 6 miembros que contiene entre uno y tres heteroátomos seleccionados en forma independiente entre O, S y N; iii) un cicloalquilo (C3-6) saturado o parcialmente insaturado; o iv) un anillo heterocíclico (C4-7) saturado o parcialmente insaturado que contiene uno o dos heteroátomos seleccionados en forma independiente entre O, S(O)p y NR17 y que opcionalmente incorpora además un grupo carbonilo; o G2 representa un sistema de anillo bicíclico en donde cada uno de los dos anillos se selecciona en forma independiente entre: i) fenilo; ii) un anillo heteroaromático de 5 ó 6 miembros que contiene entre uno y tres heteroátomos seleccionados en forma independiente entre O, S y N; iii) un cicloalquilo (C3-6) saturado o parcialmente insaturado; o iv) un anillo heterocíclico (C4-7) saturado o parcialmente insaturado que contiene uno o dos heteroátomos seleccionados en forma independiente entre O, S(O)p y NR17 y que opcionalmente incorpora además un grupo carbonilo; y los dos anillos o bien están fusionados, o están unidos directamente juntos o están separados por un grupo ligante seleccionado entre O, S(O)q o CH2, estando dicho sistema de anillo monocíclico o bicíclico opcionalmente sustituido adicionalmente por entre uno y tres sustituyentes seleccionados en forma independiente entre CN, OH, (C1-6) alquilo, (C1-6)alcoxi, halógeno, NR18R19, NO2, OSO2R38, CO2R20, C(=NH)NH2, C(O)NR21R22, C(S)NR23R24, SC(=NH)NH2, NR31C(=NH)NH2, S(O)SR25, SO2NR26R27, (C1-3)alcoxi sustituido por uno o más átomos de F y (C1-3)alquilo sustituido por SO2R39, NR56R57 o por uno o más átomos de F; o cuando L no representa un enlace, G2 también puede representar H; en cada caso, p, q, s y t en forma independiente representan un entero 0, 1 ó 2; R18 y R19 en forma independiente representan H, (C1-6)alquilo, formilo, (C2-6)alcanoilo, S(O)tR32 o SO2NR33R34; estando dicho grupo alquilo opcionalmente sustituido adicionalmente por halógeno, CN, (C1-4)alcoxi o CONR41R42; R25 representa H, (C1-6)alquilo o (C3-6)cicloalquilo; estando dicho grupo alquilo opcionalmente sustituido adicionalmente por uno o más sustituyentes seleccionados en forma independiente entre OH, CN, CONR35R36, CO2R37, OCOR40, (C3-6)cicloalquilo, un anillo heterocíclico saturado de (C4-7) que contiene uno o dos heteroátomos seleccionados en forma independiente entre O, S(O)p y R43 y fenilo o un anillo heteroaromático de 5 ó 6 miembros que contiene entre uno y tres heteroátomos seleccionados en forma independiente entre O, S y N; estando dicho anillo aromático opcionalmente sustituido adicionalmente por uno o más sustituyentes seleccionados en forma independiente entre halógeno, CN, (C1-4)alquilo, (C1-4)alcoxi, OH, CONR44R45, CO2R46, S(O)sR55 y NHCOCH3; R32 representa H, (C1-6)alquilo o C(3-6)cicloalquilo; R16, R17, R20, R21, R22, R23, R24, R26, R27, R29, R31, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R49, R50, R51, R52, R53, R54, R55, R56, R57 y R58 en forma independientemente H o (C1-6)alquilo; y sus sales aceptables para uso farmacéutico.
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