AR046789A1 - Inhibidores de fosfodiesterasa 4, que incluyen analogos de diarilamina n-sustituidos - Google Patents

Inhibidores de fosfodiesterasa 4, que incluyen analogos de diarilamina n-sustituidos

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AR046789A1
AR046789A1 ARP040104598A ARP040104598A AR046789A1 AR 046789 A1 AR046789 A1 AR 046789A1 AR P040104598 A ARP040104598 A AR P040104598A AR P040104598 A ARP040104598 A AR P040104598A AR 046789 A1 AR046789 A1 AR 046789A1
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Argentina
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alkyl
halogen
substituted
combinations
cyano
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ARP040104598A
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Memory Pharm Corp
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Abstract

Se logra la inhibición de la PDE4 utilizando compuestos, por ejemplo, análogos de diarilamina N-sustituidos. Reivindicación 1: Un compuesto de fórmula (1), donde A, B y D son cada uno N o CR5 donde al menos uno de A, B y D es N; R1 es halógeno, alquilo C1-4, alquilo halogenado C1-4, OR6, COR6, CONR6, o NR6COR10; R2 es halógeno, alquilo C1-4, alquilo halogenado C1-4 (por ejemplo, CH2F; CHF2, CF3), OR7, COR6, CONR6, o NR6COR10; R3 es alquilo C1-8 que es de cadena lineal o ramificada y que es insustituido o sustituido una o más veces por halógeno, ciano, alcoxi C1-4, o combinaciones de los mismos, un grupo alquilo carbocíclico parcialmente insaturado donde la porción carbocíclica tiene entre 5 y 14 átomos de C y la porción alquilo que es de cadena lineal o ramificada tiene entre 1 y 5 átomos de C, y que está insustituida, sustituida en la porción carbocíclica una o más veces por halógeno, alquilo, alcoxi, nitro, ciano, oxo, o combinaciones de los mismos, y/o sustituida en la porción alquilo una o más veces por halógeno, alcoxi C1-4, ciano o combinaciones de los mismos, arilalquilo con entre 7 y 19 átomos de C, donde la porción arilo tiene entre 6 y 14 átomos de C y la porción alquilo, que es de cadena lineal o ramificada, tiene entre 1 y 5 átomos de C, donde el radical arilalquilo es insustituido o sustituido, en la porción arilo, una o más veces por halógeno, trifluorometilo, CF3O, nitro, amino, alquilo, alcoxi, amino, alquilamino, dialquilamino, o combinaciones de los mismos, y/o sustituido en la porción alquilo por halógeno, ciano, alquilo C1-4, o combinaciones de los mismos, donde en la porción alquilo uno o más grupos -CH2CH2- se reemplazan cada uno optativamente por -CH=CH- o -C/C-, y/o uno o más grupos -CH2- se reemplazan cada uno optativamente por -O- o -NH-, o grupo heteroarilalquilo, donde la porción heteroarilo puede ser parcial o totalmente saturada y tiene entre 5 y 10 átomos en el anillo en donde al menos 1 átomo del anillo es un N, N-O, O o S, la porción alquilo, que es de cadena lineal o ramificada, tiene entre 1 y 5 átomos de C, el grupo heteroarilalquilo es insustituido, sustituido una o más veces en la porción heteroarilo por halógeno, alquilo, alcoxi, ciano, trifluorometilo, CF3O, nitro, oxo, amino, alquilamino, dialquilamino, o combinaciones de los mismos, y/o sustituido en la porción alquilo una o más veces por halógeno, ciano, alquilo C1-4, o combinaciones de los mismos, R4 es cicloalquilo C3-10, que es insustituido o sustituido una o más veces por halógeno, hidroxi, oxo, ciano, alquilo C1-4, alcoxi C1-4, o combinaciones de los mismos, arilo C6-14 y que es insustituido o sustituido una o más veces por halógeno, alquilo, alquenilo, alquinilo, hidroxi, alcoxi, alcoxialcoxi, nitro, metilendioxi, etilendioxi, trifluorometilo, OCF3, amino, aminoalquilo, aminoalcoxi, dialquilamino, hidroxialquilo, ácido hidroxámico, pirrolilo, tetrazol-5-ilo, 2-(-heterociclo)tetrazol-5-ilo, hidroxialcoxi, carboxi, alcoxicarbonilo, ciano, acilo, alquiltio, alquilsulfinilo, alquilsulfonilo, fenoxi, trialquilsililoxi, R8-L-, o combinaciones de los mismos; heteroarilo C5-10 en el anillo en donde al menos 1 átomo del anillo es un heteroátomo, que es insustituido o sustituido una o más veces por halógeno, alquilo, hidroxi, alcoxi, alcoxialcoxi, nitro, metilendioxi, etilendioxi, trifluorometilo, amino, aminometilo, aminoalquilo, aminoalcoxi, dialquilamino, hidroxialquilo, ácido hidroxámico, tetrazol-5-ilo, hidroxialcoxi, carboxi, alcoxicarbonilo, ciano, acilo, alquiltio, alquilsulfinilo, alquilsulfonilo, fenoxi, trialquilsililoxi, R8-L-, o combinaciones de los mismos, un grupo heterocíclico, que es saturado o parcialmente saturado, con entre 5 y 10 átomos en el anillo en donde al menos 1 átomo del anillo es un átomo de N, O o S, que es insustituido o sustituido una o más veces por halógeno, alquilo, hidroxi, alcoxi, alcoxialcoxi, nitro, oxo, metilendioxi, etilendioxi, trifluorometilo, OCF3, amino, aminometilo, aminoalquilo, aminoalcoxi, dialquilamino, hidroxialquilo, ácido hidroxámico, tetrazol-5-ilo, hidroxialcoxi, carboxi, alcoxicarbonilo, ciano, acilo, alquiltio, alquilsulfinilo, alquilsulfonilo, fenilsulfonilo, fenoxi, cicloalquilo, arilo, heteroarilo o combinaciones de los mismos, un grupo alquilo heterocíclico, donde la porción heterocíclica es saturada, parcialmente saturada o insaturada, y tiene entre 5 y 10 átomos en el anillo en donde al menos 1 átomo del anillo es un átomo de N, O o S, y la porción alquilo es de cadena lineal o ramificada y tiene entre 1 y 5 átomos de C, el grupo alquilo heterocíclico es insustituido, sustituido una o más veces en la porción heterocíclica por halógeno, alquilo, hidroxi, alcoxi, alcoxialcoxi, nitro, oxo, metilendioxi, etilendioxi, trifluorometilo, OCF3, amino, aminometilo, aminoalquilo, aminoalcoxi, dialquilamino, hidroxialquilo, ácido hidroxámico, tetrazol-5-ilo, hidroxialcoxi, carboxi, alcoxicarbonilo, ciano, acilo, alquiltio, alquilsulfinilo, alquilsulfonilo, fenilsulfonilo, fenoxi, cicloalquilo, arilo, heteroarilo o combinaciones de los mismos, y/o sustituida en la porción alquilo una o más veces por halógeno, oxo, hidroxi, ciano, o combinaciones de los mismos, y donde en la porción alquilo uno o más grupos -CH2CH2- se reemplazan cada uno optativamente por -CH=CH- o -C/C-, y uno o más grupos -CH2- se reemplazan cada uno optativamente por -O- o -NH; R5 es H, halógeno, alquilo C1- 4, alcoxi C1-4, o alquilo halogenado C1-4, alcoxi C1-4 o aloxi halogenado C1-4 ; R6 es H o alquilo C1-4, que es de cadena lineal o ramificada y que es insustituido o sustituido una o más veces por halógeno; R7 es H o alquilo C1-12 que es de cadena lineal o ramificada y que es insustituido o sustituido una o más veces por halógeno, hidroxi, ciano, alcoxi C1-4, oxo o combinaciones de los mismos, y donde optativamente uno o más grupos -CH2CH2- se reemplaza en cada caso por -CH=CH- o -C/C-, cicloalquilo C3-10 que es insustituido o sustituido una o más veces por halógeno, hidroxi, oxo, ciano, alquilo C1-4, alcoxi C1-4, o combinaciones de los mismos, cicloalquilalquilo C4-16 que es insustituido o sustituido en la porción cicloalquilo y/o la porción alquilo una o más veces por halógeno, oxo, ciano, hidroxi, alquilo C1-4, alcoxi C1-4 o combinaciones de los mismos; arilo C6-14 y que es insustituido o sustituido una o más veces por halógeno, CF3, OCF3, alquilo, hidroxi, alcoxi, nitro, metilendioxi, etilendioxi, ciano, o combinaciones de los mismos(por ejemplo metilfenilo, metoxifenilo, clorofenilo, etc); arilalquilo en donde la porción arilo tiene entre 6 y 14 átomos de C y la porción alquilo, que es de cadena lineal o ramificada, tiene entre 1 y 5 átomos de C, donde el radical arilalquilo es insustituido, sustituido, en la porción arilo una o más veces por halógeno, CF3, OCF3, alquilo, hidroxi, alcoxi, nitro, ciano, metilendioxi, etilendioxi, o combinaciones de los mismos, y/o sustituida en la porción alquilo una o más veces por halógeno, oxo, hidroxi, ciano, o combinaciones de los mismos, y donde en la porción alquilo uno o más grupos -CH2CH2- se reemplazan cada uno optativamente por -CH=CH- o -C/C-, y uno o más grupos -CH2-se reemplazan cada uno optativamente por -O- o -NH- , un grupo carbocíclico parcialmente insaturado con entre 5 y 14 átomos de C, que es insustituido o sustituido una o más veces por halógeno, alquilo, alcoxi, hidroxi, nitro, ciano, oxo, o combinaciones de los mismos, un grupo heterocíclico, que es saturado, parcialmente saturado o insaturado, con entre 5 y 10 átomos en el anillo en donde al menos 1 átomo del anillo es un átomo de N, O o S, que es insustituido o sustituido una o más veces por halógeno, hidroxi, arilo, alquilo, alcoxi, ciano, trifluorometilo, nitro, oxo, o combinaciones de los mismos, o un grupo alquilo heterocíclico, donde la porción heterocíclica es saturada, parcialmente saturada o insaturada, y tiene entre 5 y 10 átomos en el anillo en donde al menos 1 átomo del anillo es un átomo de N, O o S, y la porción alquilo es de cadena lineal o ramificada y tiene entre 1 y 5 átomos de C, el grupo alquilo heterocíclico es insustituido, sustituido una o más veces en la porción heterocíclica por halógeno, OCF3, hidroxi, arilo, alquilo, alcoxi, ciano, trifluorometilo, nitro, oxo, o combinaciones de los mismos, y/o sustituida en la porción alquilo una o más veces por halógeno, oxo, hidroxi, ciano, o combinaciones de los mismos, y donde en la porción alquilo uno o más grupos -CH2CH2- se reemplazan cada uno optativamente por -CH=CH- o -C/C-, y uno o más grupos -CH2- se reemplazan cada uno optativamente por -O- o -NH-; R8 es H, alquilo C1-8 que es insustituido o sustituido una o más veces por halógeno, alquilo C1-4, alcoxi C1-4, oxo, o combinaciones de los mismos, alquilamino o dialquilamino donde cada porción alquilo tiene en forma independiente entre 1 y 8; un grupo alquilo carbocíclico parcialmente insaturado donde la porción carbocíclica tiene entre 5 y 14 átomos de C y la porción alquilo tiene entre 1 y 5 átomos de C, y que es insustituido o sustituido una o más veces por halógeno, alquilo, alcoxi, nitro, ciano, oxo, o combinaciones de los mismos, cicloalquilo C3-10 que es insustituido o sustituido una o más veces por halógeno, hidroxi, oxo, ciano, alcoxi, alquilo C1-4, o combinaciones de los mismos, cicloalquilalquilo C4-16 que es insustituido o sustituido en la porción cicloalquilo y/o la porción alquilo una o más veces por halógeno, oxo, ciano, hidroxi, alquilo, alcoxi o combinaciones de los mismos, arilo C6-14 que es insustituido o sustituido una o más veces por halógeno, alquilo, hidroxi, alcoxi, alcoxialcoxi, nitro, metilendioxi, etilendioxi, trifluorometilo, amino, aminometilo, aminoalquilo, aminoalcoxi, dialquilamino, hidroxialquilo, ácido hidroxámico, tetrazol-5-ilo, hidroxialcoxi, carboxi, alcoxicarbonilo, ciano, acilo, alquiltio, alquilsulfinilo, alquilsulfonilo, fenoxi, cicloalquilo, arilo, heteroarilo o combinaciones de los mismos; arilalquilo C7-19, donde la porci
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