AR064531A1 - Derivados de isoquinolina e isoquinolinona sustituidos con cicloalquilamina y su uso en la fabricacion de medicamentos para el tratamiento de enfermedades mediadas por la inhibicion de la rho-quinasa - Google Patents

Derivados de isoquinolina e isoquinolinona sustituidos con cicloalquilamina y su uso en la fabricacion de medicamentos para el tratamiento de enfermedades mediadas por la inhibicion de la rho-quinasa

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AR064531A1
AR064531A1 ARP070105898A ARP070105898A AR064531A1 AR 064531 A1 AR064531 A1 AR 064531A1 AR P070105898 A ARP070105898 A AR P070105898A AR P070105898 A ARP070105898 A AR P070105898A AR 064531 A1 AR064531 A1 AR 064531A1
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alkyl
alkylene
aryl
heterocyclyl
substituted
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Sanofi Aventis
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Abstract

Derivados de isoquinolina e isoquinolinona 6-sustituidos de la formula (1) utiles para el tratamiento y/o prevencion de enfermedades asociadas con la Rho-quinasa y/o la fosforilacion mediada por la Rho-quinasa de la fosfatasa de la cadena ligera de miosina, y a su uso en la preparacion de medicamentos que contienen tales compuestos. Reivindicacion 1: Un compuesto de la formula (1) en la que R1 es H, OH o NH2, R2 es R', alquilo C7-8, alquileno C1-6-R', alquenilo C2-6, alquinilo C2-6, alquileno C1-6-O-R', alquileno C1-6-CH[R']2, alquileno C1-6-C(O)-R', alquileno C1-6-C(O)NH2, alquileno C1-6-C(O)NH-R' alquileno C1-6-C(O)NH-alquilo C1-6, alquileno C1-6-C(O)N[alquilo C1-6]2, alquileno C1-6-C(O)N[R']2; alquileno C1-6-C(O)O-alquilo C1- 6, C(O)O-alquilo C1-6, C(O)OR', C(O)-alquilo C1-6, C(O)R', C(O)NH-alquenilo C2-6, C(O)-NH-alquinilo C2-6, C(O)-NH-alquinilo C1-6, C(O)NHR', C(O)-NH-alquileno C1-6-R', C(O)N[alquilo C1-6]R', C(O)N[alquilo C1-6]2, C(O)-alquileno C1-6-R', C(O)O- alquileno C1-6-R'; o R2 es alquilo C1-6, con la condicion de que en dicho resto alquilo al menos un H esta sustituido con OH, OCH3, COOH, COOCH3, NH2, NHCH3, N(CH3)2, CONH2, CONHCH3 o CON(CH3)2; o R2 es un alquileno C1-4 unido a la cicloalquilamina, donde el alquileno C1-4 forma un segundo enlace con un átomo de carbono diferente del anillo de cicloalquilamina y forma, junto con átomos de C de la cicloalquilamina, un segundo anillo de 4-8 miembros; R3 es H, halogeno, alquilo C1-6, alquileno C1- 6-R', OH, O-Rö, NH2, NHRö, NRöRö o NH-C(O)-Rö, R4 es H, halogeno, hidroxi, CN, alquilo C1-6, R', alquileno C1-6-R'; R5 es H, halogeno, CN, NO2, alquilo C1-6, alquenilo C2-6, R', alquileno C1-6-arilo C6-10, alquenileno C1-6-arilo C6-10, alquileno C1- 6-heterociclilo C5-10, CH(OH)-alquilo C1-6, NH2, NH-R', NH-SO2H, NH-SO2-alquiIo C1-6, NH-SO2-R', NH-C(O)-alquilo C1-6, NH-C(O)-R', C(O)N[alquilo C1-6]2, C(O)OH, o C(O)O-alquilo C1-6; R6 y R6' son independientemente entre sí H, R', alquilo C1-8, alquileno C1-6-R', alquileno C1-6-O-alquilo C1-6, alquileno C1-6-O-R', alquileno C1-6-CH[R']2, alquileno C1-6-C(O)-R', alquileno C1-6-C(O)NH2, alquileno C1-6-C(O)NH-R', alquileno C1-6-C(O)NH-alquilo C1-6, alquileno C1-6-C(O)N[alquilo C1-6]2, alquileno C1-6-C(O)N[R']2, alquileno C1-6-C(O)O-alquilo C1-6, C(O)O-alquilo C1-6, C(O)OR', C(O)-alquilo C1-6, C(O)R', C(O)NH-alquilo C1-6, C(O)NHR', C(O)N[alquil C1-6]R', C(O)N[alquilo C1-6]2, C(O)-alquileno C1-6-R', C(O)O-alquileno C1-6-R', o R6 y R6', junto con el átomo de N al que están unidos, forman un grupo heterociclilo C5-10; R7 es H, halogeno, CN, NO2, alquilo C1-6, O-alquilo C1-6, alquenilo C2-6, R', alquenileno C1-6-arilo C6-10, alquileno C1-6-R', CH(OH)-alquilo C1-6, NH2, NH-R', NH- SO2H, NH-SO2-alquilo C1-6, NH-SO2-R', SO2-NH2, SO2-NHR', NH-C(O)-alquilo C1-6, NH-C(O)-R', C(O)N[alquilo C1-6]2, C(O)OH, o C(O)O-alquilo C1-6; R8 es H, halogeno o alquilo C1-6; n es 1, 2, 3 o 4; m es 1, 2, 3, 4 o 5; r es 0, 1 o 2 y L es O(CH2)p, S(CH2)p, S(O)(CH2)p, S(O)2(CH2)p, NH(CH2)p, N-alquil C1-6-(CH2)p, N-cicloalquil C3-6-(CH2)p, N[CO-alquil C1-6]-(CH2)p o N[alquileno C1-3)-R']-(CH2)p; p es 0, 1, 2, 3 o 4; donde R' es cicloalquilo C3-8, heterociclilo C5-10, arilo C6-10; Rö es cicloalquilo C3-8, heterociclo C5-10, arilo C6-10, alquilo C1-6, alquileno C1-6-R', alquileno C1-6-O-alquilo C1-6, alquileno C1-6-O-R', o alquileno C1-6-NRxRy; y donde Rx, y Ry son independientemente entre sí alquilo C1-6, heterociclilo C5-10, arilo C6-10, alquileno C1-4-heterociclilo C5-10, alquileno C1-4-arilo C6-10, alquileno C1-4-NH-alquilo C1-6, alquileno C1-4-NH[alquilo C1-6]2, alquileno C1-4-N[arilo C6-10]2, o alquileno C1-4-N[heterociclilo C5-10]2; donde en los restos R2, R4, R5, R6, R6', R7 y R8, el grupo alquilo, alquileno o cicloalquilo pueden estar opcionalmente sustituidos una o más veces con OH, OCH3, COOH, COOCH3, NH2, NHCH3, N(CH3)2, CONH2, CONHCH3 o CON(CH3)2; donde en los restos R2 a R8, los grupos alquilo o alquileno pueden estar opcionalmente sustituidos una o más veces con halogeno; donde en los restos R2 a R8, los grupos arilo C6-10 y heterociclilo C5-10 están sin sustituir o sustituidos una o más veces con grupos adecuados seleccionados independientemente entre halogeno, OH, NO2, N3, CN, C(O)-alquilo C1-6, C(O)-arilo C1-6, COOH, COO-alquilo C1-6, CONH2, CONH-alquilo C1-6, CON[alquilo C1-6]2, cicloalquilo C3-8, alquilo C1-6, alquileno C1-6-OH, alquileno C1-6-NH2, alquileno C1-6-NH-alquilo C1-6, alquileno C1-6-N[alquilo C1-6]2, alquenilo C2-6, alquinilo C2-6, O-alquilo C1-6, O-C(O)-alquilo C1-6, PO3H2, SO3H, SO2-NH2, SO2NH-alquilo C1-6, SO2N[alquilo C1-6]2, S-alquilo C1-6; SO-alquilo C1-6, SO2-alquilo C1-6, SO2-N=CH-N[alquiIo C1-6]2, C(NH)(NH2), NH2, NH-alquilo C1-6, N[aIquiIo C1-6]2, NH-C(O)-alquilo C1-6), NH-C(O)O-alquilo C1-6, NH-SO2-alquilo C1-6, NH-SO2-arilo C6-10, NH-SO2-heterociclilo C5-10, N-alquil C1-6-C(O)-alquilo C1-6, N-alquil C1-6-C(O)O-alquilo C1-6, N-alquil C1-6- C(O)-NH-alquilo C1-6], arilo C6-10, alquileno C1-6-arilo C6-10, O-arilo C6-10, O-alquileno C1-6-arilo C6-10, heterociclilo C5-10, alquiIeno C1-6-heterociclilo C5-10, O-alquileno C1-6-heterociclilo C5-10, donde los grupo arilo C6-10 o heterociclilo C5-10 pueden estar sustituidos de una a tres veces con un grupo seleccionado independientemente entre halogeno, OH, NO2, CN, O-alquilo C1-6, alquilo C1-6, NH2, NH-alquilo C1-6, N[alquilo C1-6]2, SO2CH3, COOH, C(O)O-alquilo C1-6, CONH2, alquileno C1- 6-O-aIquilo C1-6, alquileno C1-6-O-arilo C6-10, u O-alquileno C1-6-arilo C6-10; o donde el grupo arilo C6-10 está sustituido vecinalmente con un grupo O-alquileno C1-4-O, por lo que se forma, junto con los átomos de carbono a los que están unidos los átomos de oxígeno, un anillo de 5-8 miembros, y donde los sustituyentes arilo o heterociclilo de los grupos arilo C6-10 y heterociclilo C5-10 no pueden estar adicionalmente sustituidos con un grupo que contiene arilo o heterociclilo; o sus formas estereoisoméricas y/o tautoméricas y/o sus sales farmacéuticamente aceptables.
ARP070105898A 2006-12-27 2007-12-26 Derivados de isoquinolina e isoquinolinona sustituidos con cicloalquilamina y su uso en la fabricacion de medicamentos para el tratamiento de enfermedades mediadas por la inhibicion de la rho-quinasa AR064531A1 (es)

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