AR041066A1 - 2,5-dioxoimidazolidin-4-il-acetamidas y analogos como inhibidores de la metaloproteinasa mmp12 - Google Patents

2,5-dioxoimidazolidin-4-il-acetamidas y analogos como inhibidores de la metaloproteinasa mmp12

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Publication number
AR041066A1
AR041066A1 ARP030103098A ARP030103098A AR041066A1 AR 041066 A1 AR041066 A1 AR 041066A1 AR P030103098 A ARP030103098 A AR P030103098A AR P030103098 A ARP030103098 A AR P030103098A AR 041066 A1 AR041066 A1 AR 041066A1
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Argentina
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alkyl
ring
halogen
hydroxyl
optionally substituted
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ARP030103098A
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English (en)
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Krister Henriksson
Magnus Munck Af Rosenschold
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Astra Ab
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Publication of AR041066A1 publication Critical patent/AR041066A1/es

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    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/72—Two oxygen atoms, e.g. hydantoin
    • C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
    • C07D233/78—Radicals substituted by oxygen atoms
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    • A61K31/4164—1,3-Diazoles
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    • C07D401/12—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 chain containing hetero atoms as chain links
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    • 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
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Abstract

2,5-Dioxoimidazolidin-4-il-acetamidas y análogos como inhibidores de la metaloproteinasa MMP12, procesos para su preparación, composiciones farmacéuticas que las comprenden; un proceso para preparar las composiciones farmacéuticas y su uso terapéutico. Reivindicación 1: Un compuesto caracterizado porque responde a la fórmula (1) o una sal o solvato aceptable para uso farmacéutico del mismo donde: X representa un átomo de O o un grupo NR4 o CH2; Y representa NH o N-metilo; Z1 y Z2 representan cada uno en forma independiente un átomo de O o S, con la condición de que al menos uno entre Z1 y Z2 represente un átomo de O; R1 representa H o un grupo seleccionado entre C1-6 alquilo y un sistema de anillos saturado o insaturado de 3 a 10 miembros que puede contener al menos un heteroátomo en el anillo seleccionado entre N; O y S, donde cada grupo está opcionalmente sustituido con al menos un sustituyente entre halógeno, hidroxilo, ciano, carboxilo, -NR5R6, -CONR7R8, C1-6alquilo, C1-6alcoxi, C1-6 alquilcarbonil(oxi), -S(O)mC1-6alquilo donde m es 0, 1, o 2, C1-6 alquilsulfonilamino, C1-6alcoxicarbonil(amino), benciloxi y un anillo saturado o insaturado de 5 a 6 miembros que puede contener al menos un heteroátomo en el anillo seleccionado entre H, O, y S, donde a su vez el anillo está sustituido con al menos un sustituyente seleccionado entre halógeno, hidroxilo, oxo, carboxilo, ciano, C1-6 alquilo, C1-6 alcoxicarbonilo y C1-6 hidroxialquilo; R2 representa H o C1-6 alquilo y R3 representa H o C1-6 alquilo, o R1 y R2 junto con los átomos de C a los cuales están unidos forman un anillo saturado de 5 a 6 miembros que contiene opcionalmente un heteroátomo en el anillo seleccionado entre H, O, y S, y R3 es como se define anteriormente, o R2 y R3 junto con el átomo de C al cual están unidos forman un anillo saturado de 5 a 6 miembros que contiene opcionalmente un heteroátomo en el anillo seleccionado entre N, O, y S, y R1 es como se define anteriormente; R4 representa H o C1-6 alquilo; R5, R6, R7 y R8 representan cada uno en forma independiente H o C1-6 alquilo sustituido opcionalmente con al menos un sustituyente seleccionado entre hidroxilo, halógeno y C1-6alcoxi; L representa -CH2C(O)- o -C(O)CH2-, o L representa un grupo C2-6 alquilo o C2-6 alquinilo opcionalmente interrumpido o terminado por al menos una porción seleccionada entre O, NH, S, SO, SO2 y C(O), o L representa un grupo C3-6cicloalquilo, metil C3-6cicloalquilo o C3-6cicloalquilmetilo, donde cada grupo enumerado está opcionalmente sustituido con al menos un sustituyente seleccionado entre hidroxilo, halógeno, C1-4 alquilo, C1-4 haloalquilo, C1-4 alcoxi y C1-4 haloalcoxi, o L representa una cadena C3-4 alquileno, cuyos extremos están unidos a átomos de C del anillo adyacentes en el sistema de anillos de 5 a 10 miembros de G2 para formar un anillo, G2 representa un sistema de anillos saturado o insaturado de 5 a 10 miembros que puede contener al menos un heteroátomo en el anillo seleccionado entre N, O y S, donde el sistema de anillos está opcionalmente sustituido con al menos un sustituyente seleccionado entre halógeno, hidroxilo, ciano, nitro, C1-6 alquilo (sustituido opcionalmente con uno o más de ciano, halógeno, hidroxilo y metoxi), C2-6 alquenilo, C1-6 alcoxi (sustituido opcionalmente con uno o más átomos de halógeno), -S(O)nC1-6alquilo donde n es 0, 1 o 2, C1-6 alquilcarbonil(amino), C1-6alquilcarboniloxi, fenilo, benciloxi, -NR9R10 y un grupo de la fórmula (2); R9 y R10 representan cada uno en forma independiente H o C1-6 alquilo sustituido opcionalmente con al menos un sustituyente seleccionado entre hidroxilo, halógeno y C1-6 alcoxi; M representa un enlace o -O-, -S-, -C=C-, -CH2O- o -OCH2-; G3 representa un sistema de anillos insaturado de 5 a 10 miembros que puede contener al menos un heteroátomo en el anillo seleccionado entre N, O y S, donde el sistema de anillos está opcionalmente sustituido con al menos un sustituyente seleccionado entre halógeno, hidroxilo, ciano, nitro, C1-6 alquilo (sustituido opcionalmente con uno o más de ciano, halógeno, hidroxilo y metoxi), C2-6 alquenilo, C1-6 alcoxi (sustituido opcionalmente con uno o más átomos de halógeno), -S(O)tC1-6 alquilo donde t es 0, 1 o 2, C1-6 alquilcarbonil(amino), C1-6 alquilcarboniloxi, fenilo, benciloxi y -NR11R12, y R11 y R12 representan cada uno en forma independiente H o C1-6 alquilo sustituido opcionalmente con al menos un sustituyente seleccionado entre hidroxilo, halógeno y C1-6 alcoxi.
ARP030103098A 2002-08-27 2003-08-27 2,5-dioxoimidazolidin-4-il-acetamidas y analogos como inhibidores de la metaloproteinasa mmp12 AR041066A1 (es)

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EP (1) EP1542977B1 (es)
JP (1) JP2006503019A (es)
KR (1) KR20050059093A (es)
CN (1) CN100398521C (es)
AR (1) AR041066A1 (es)
AT (1) ATE348816T1 (es)
AU (1) AU2003253557B2 (es)
BR (1) BR0313635A (es)
CA (1) CA2495853A1 (es)
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