ECSP034475A - Derivados de 4-fenil-piridin como antagonistas del receptor de neuroquinina-1 - Google Patents

Derivados de 4-fenil-piridin como antagonistas del receptor de neuroquinina-1

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Publication number
ECSP034475A
ECSP034475A EC2003004475A ECSP034475A ECSP034475A EC SP034475 A ECSP034475 A EC SP034475A EC 2003004475 A EC2003004475 A EC 2003004475A EC SP034475 A ECSP034475 A EC SP034475A EC SP034475 A ECSP034475 A EC SP034475A
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Ecuador
Prior art keywords
lower alkyl
halogen
cyano
hydroxy
hydrogen
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EC2003004475A
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English (en)
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Thierry Godel
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Hoffmann La Roche
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Publication of ECSP034475A publication Critical patent/ECSP034475A/es

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Abstract

La presente invención se regiere a compuestos con fórmula general (gráfico) donde r es hidrógeno 0 halógeno R1 es-(C=C) mR1 o -CR´ =CR") mR1 donde R1 es a) halógeno, t B) ciano, o los siguientes grupos: (Gráfico) d) -C(NR'r", e) -C(0)0(CH2)mR5, f) -C(0)R5, g) -N(OH)-(CH2)mR5, h) -NR'C(0)-(CH2)mR5, i) -N [C(0)-R']2, j -OR6, -(CH2)m-SR6,-(CH2)m-S(0)R6, o-(CH2)m-S(0)2R6. 1) Arilo,opcionalmente sustituido para uno o más sustituyentes, seleccionados a partir de halógeno, trifluorometilo, alquilo inferior, alcoxi inferior, ciano, hidroxi, -NR'R", nitro,-(CH2)nOR', -C(O)NR'R", -C(0)OR'or-C(O)R', m) es un grupo heteroarilo de cinco o seis miembros, conteniendo de uno a cuatro heteroátomos, seleccionandos a partir de N,0 6 ó S y puede ser opcionalmente sustituido por uno o más sustituyentes, seleccionados a partir de halógeno, trifluorometilo, alquilo inferior, alcoxi inferior, ciano, hidroxi, -NR'R", nitro, -(CH2)nOR', -C(0)OR', - C(0)NR'R" 0 -C(=)R', n) es una amina terciaria cíclica saturada de cinco o seis miembros, del grupo la cual puede contener un heteroátomo adicional, sleccionado entre N, 00 S. R'R" son, independientemente uno de otro, hidrógeno, hidroxi, alquilo inferior, cicloalquilo ó arilo, donde el alquilo inferior, grupos cicloalquilo ó arilo pueden ser opcionalmente sustituídos por uno o más sustituyentes, ' seleccionados a partir de halógeno, trifluorometilo, alquilo inferior, alcoxi inferior, ciano, hidroxi, -NR"'R"", nitro, (CH2)nOR"', -c(0)NR"'r"", -C(0)OR"' O -C(0)R"". R"'/R"" son, independientemente uno de otro, hidrógeno, alquilo inferior, cicloalquilo o arilo, R5 es hidrógeno, ciano, hidroxi, halógeno, trifluorometilo, -C(0)OR', OC(0)R', -OC(0)R 0 arilo, opcionalmente sustituidos por uno o más sustituyentes seleccionados a partir de halógeno, trifluorometilo, alquilo inferior, alcoxi inferior, ciano, hidroxi, -NR'R", nitro, -(CHZ)nOR', -C(0)NR'R", -C(0) OR' o-C(0)OR', o es un grupo heteroarilo de cinco o seis miembros,conteniendo de uno a cuatro heteroatomos, seleccionados a partir de N, 0 o S y puede ser opcionalmente sustituido por uno o más sustituyentes, seleccionados a partir de halógeno, trifluorometilo, alquilo inferior, alcoxi inferior, ciano, hidroxi, -NR'R", nitro, -(CH2) n OR', -C(0)NR'R", -C(0) OR' or -C to) R', R6 es hidrógeno, alquilo inferior, trifluorometilo, o arilo, donde el alquilo inferior o el grupo arilo pueden ser opcionalmente sustituidos por uno o más sustituyentes seleccionados a partir de halógeno, trifluorometilo, alquilo inferior , alcoxi inferior, ciano, hidroxi, -NR'R", nitro, -(CH2)nOR', -(CH2)nOR', -C(0)OR', -C(0)OR' o -C(0)R', o es un grupo heteroarilo de cinco o seis miembros, conteniendo de uno a cuatro heteroatomos, seleccionados a partir de N, 0 o S y puede ser opcionalmente sustituidos por uno o más sustituyentes, seleccionados a partir de halógeno, trifluorometilo, alquilo inferior, ciano, hidroxi, -NR'R", nitro -(CHz)nOR', -c(0) NR'R"' -c(0)OR'0 -C(0)R', R7 ES -C(0) -(CHZ)m OH o un grupo oxo; R2 hidrógeno, alquilo inferior, alcoxi inferior, halógeno o CF3; R3/R3, son independientemente uno de otro hidrógeno , alquilo inferior o forman juntos, con el átomo de carbón con el que se unen, un grupo cicloalquilo; R4/R4, son independientemente uno de otro hidrógeno, halógeno, CF3, alquilo inferior o alcoxi inferior; r y R2 o R4 y R4, pueden ser juntos -CH=CH=CH=CH-, opcionalmente sustituidos por uno o dos sustituyentes seleccionados a partir de alquilo inferior, halógeno o alcoxi inferior; X es -C(0) N(R8)-, (CH2)p0-, (CH2)pN(R8)-, -N(R8)C(0)-o -N(R8)- (CH2)p; donde R8 es hidrógeno o alquilo inferior ; n es 1 o 2; m es 0,1,2,3 o 4; o es 1 o 2; y p es 1 o 2; y sales de adición de ácido farmacéuticamente aceptables. Se ha encontrado que los compuestos de la presente invención son antagonistas del receptor de la Neuroquinina 1 (NK-1, sustancia P), y por lo tanto son útiles para el tratamiento de enfermedades relacionadas con este receptor.
EC2003004475A 2000-08-08 2003-02-07 Derivados de 4-fenil-piridin como antagonistas del receptor de neuroquinina-1 ECSP034475A (es)

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