ES2680820T3 - Derivados de azaspiro(4,5)decano sustituidos - Google Patents

Derivados de azaspiro(4,5)decano sustituidos Download PDF

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ES2680820T3
ES2680820T3 ES15737988T ES15737988T ES2680820T3 ES 2680820 T3 ES2680820 T3 ES 2680820T3 ES 15737988 T ES15737988 T ES 15737988T ES 15737988 T ES15737988 T ES 15737988T ES 2680820 T3 ES2680820 T3 ES 2680820T3
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nhr0
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Anita Wegert
Bert Nolte
Klaus Linz
Stephanie Harlfinger
Babette-Yvonne Kögel
Paul Ratcliffe
Fritz Theil
Olga GRÖGER
Birgit Braun
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Gruenenthal GmbH
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Abstract

Un compuesto de la fórmula general (1)**Fórmula** donde Y1, Y1', Y2, Y2', Y3, Y3', Y4 e Y4' en cada caso se eligen independientemente entre sí de entre el grupo que consiste en -H, -F, -Cl, -Br, -I, -CN, -NO2, -CHO, -R0, -C(>=O)R0, -C(>=O)H, -C(>=O)-OH, -C(>=O)OR0, -C(>=O)NH2, -C(>=O)NHR0, - C(>=O)N(R0)2, -OH, -OR0, -OC(>=O)H, -OC(>=O)R0, -OC(>=O)OR0, -OC(>=O)NHR0, -OC(>=O)N(R0)2, -SH, -SR0, -SO3H, - S(>=O)1-2-R0, -S(>=O)1-2NH2, -NH2, -NHR0, -N(R0)2, -N+(R0)3, -N+(R0)2O-, -NHC(>=O)R0, -NHC(>=O)OR0, -NHC(>=O)NH2, - NHC(>=O)NHR0 y -NHC(>=O)N(R0)2; o Y1 e Y1', o Y2 e Y2', o Y3 e Y3', o Y4 e Y4' representan conjuntamente >=O; X1, X1', X2, X2', X3 y X3' en cada caso representan independientemente entre sí -H, -F, -Cl, -Br, -I, -NO2, -CF3, -OR5, - SR5, -SO2R5, -S(>=O)2OR5, -CN, -COOR5, -CONR5, -NR6R7, o -R0; o X1 y X1', o X2 y X2', o X3 y X3' representan conjuntamente >=O; o X1 y X2, o X2 y X3 representan conjuntamente -(CH2)2-6-, donde los átomos de hidrógeno individuales también pueden estar sustituidos por -F, -Cl, -Br, -I, -NO2, -CF3, -OR5, -CN o -C1-6-alifático; o X1 y X1', o X2 y X2' o X3 y X3' representan conjuntamente un C3-6-cicloalifático, donde los átomos de hidrógeno individuales también pueden estar sustituidos por -F, -Cl, -Br, -I, -NO2, -CF3, -OR5, -CN o -C1-6-alifático; R0 en cada caso representa independientemente -C1-8-alifático, -C3-12-cicloalifático, -arilo, -heteroarilo, -C1-8-alifático- C3-12-cicloalifático, -C1-8-alifático-arilo, -C1-8-alifático-heteroarilo, -C3-8-cicloalifático-C1-8-alifático, -C3-8-cicloalifáticoarilo o -C3-8-cicloalifático-heteroarilo; R1 y R2 representan independientemente entre sí -H o -R0; o R1 y R2 representan conjuntamente -CH2CH2OCH2CH2- , -CH2CH2NR8CH2CH2- o -(CH2)3-6-; R3 representa -R0; R4 representa H o -Z-R11, donde Z puede estar ausente o -C(>=O)-, -S(>=O)- o -S(>=O)2-, y R11 representa -C1-6-alquilo, -C3-6-cicloalquilo o -C1-3-alquil-C3-6-cicloalquilo, donde en el grupo C3-6-cicloalquilo un átomo de carbono del anillo puede estar sustituido por un átomo de oxígeno y -C1-6-alquilo, -C3-6-cicloalquilo o -C1-3- alquil-C3-6-cicloalquilo puede estar no sustituido, monosustituido o polisustituido con sustituyentes seleccionados de entre el grupo que consiste en -F, -Cl, -Br, -I, -CN, -OH, -SH, -O-C1-3-alquilo y -S-C1-3-alquilo, donde -C1-3-alquilo puede estar sustituido por uno o más sustituyentes de entre el grupo que incluye los sustituyentes -F, -Cl, -Br, - I, -CN, -OH, -SH; R5 en cada caso representa independientemente -H o -R0; R6 y R7 representan independientemente entre sí -H o -R0; o R6 y R7 representan conjuntamente -CH2CH2OCH2CH2- , -CH2CH2NR10CH2CH2- o -(CH2)3-6-; R8 representa -H, -R0 o -C(>=O)R0; R10 representa -H o -C1-6-alifático; donde "alifático" es en cada caso un radical de hidrocarburo alifático, ramificado o no ramificado, saturado o monoinsaturado o poliinsaturado, no sustituido o monosustituido o polisustituido; "cicloalifático" es en cada caso un radical de hidrocarburo saturado o monoinsaturado o poliinsaturado, no sustituido o monosustituido o polisustituido, alicíclico, monocíclico o multicíclico; donde con respecto a "alifático" y "cicloalifático", se entiende que "monosustituido o polisustituido" significa la sustitución de uno o más átomos de hidrógeno por -F, -Cl, -Br, -I, -CN, -NO2, -CHO, >=O, -R0, -C(>=O)R0, -C(>=O)H, - C(>=O)-OH, -C(>=O)OR0, -C(>=O)NH2, -C(>=O)NHR0, -C(>=O)N(R0)2, -OH, -OR0, -OC(>=O)H, -OC(>=O)R0, - OC(>=O)OR0, -OC(>=O)NHR0, -OC(>=O)N(R0)2, -SH, -SR0, -SO3H, -S(>=O)1-2-R0, -S(>=O)1-2NH2, -NH2, -NHR0, -N(R0)2, - N+(R0)3, -N+(R0)2O-, -NHC(>=O)R0, -NHC(>=O)OR0, -NHC(>=O)NH2, -NHC(>=O)NHR0, -NH-C(>=O)N(R0)2, -Si(R0)3, - PO(OR0)2; "arilo" en cada caso representa independientemente un sistema de anillo carbocíclico que tiene al menos un anillo aromático, pero sin heteroátomos en este anillo, donde los radicales arilo pueden estar fusionados opcionalmente con sistemas de anillos adicionales saturados, (parcialmente) insaturados o aromáticos y cada radical arilo puede estar no sustituido o monosustituido o polisustituido, donde los sustituyentes en el arilo pueden ser idénticos o diferentes y pueden estar en cualquier posición deseada y posible del arilo; "heteroarilo" representa un radical aromático cíclico de 5, 6 o 7 miembros que contiene 1, 2, 3, 4 o 5 heteroátomos, donde los heteroátomos son idénticos o diferentes y son nitrógeno, oxígeno o azufre y el heterociclo puede estar no sustituido o monosustituido o polisustituido; donde en el caso de sustitución en el heterociclo los sustituyentes pueden ser idénticos o diferentes y pueden estar en cualquier posición deseada y posible del heteroarilo; y donde el heterociclo puede también formar parte de un sistema bicíclico o policíclico; donde con respecto a "arilo" y "heteroarilo", se entiende que "monosustituido o polisustituido" significa la sustitución una o varias veces de uno o más átomos de hidrógeno del sistema del anillo por sustituyentes elegidos de entre el grupo que consiste en -F, -Cl, -Br, -I, -CN, -NO2, -CHO, >=O, -R0, -C(>=O)R0, -C(>=O)H, -C(>=O)OH, -C(>=O)OR0, - C(>=O)NH2, -C(>=O)NHR0, -C(>=O)-N(R0)2, -OH, -O(CH2)1-2O-, -OR0, -OC(>=O)H, - OC(>=O)R0, -OC(>=O)OR0, -OC(>=O)NHR0, -OC(>=O)N(R0)2, -SH, -SR0, -SO3H, -S(>=O)1-2-R0, -S(>=O)1-2NH2, - NH2, -NHR0, -N(R0)2, -N+(R0)3, -N+(R0)2O-, -NHC(>=O)R0, -NHC(>=O)OR0, -NH-C(>=O)NH2, -NHC(>=O)NHR0, - NHC(>=O)N(R0)2, -Si(R0)3, -PO(OR0)2; donde N átomos del anillo presentes opcionalmente pueden estar en cada caso oxidados (N-óxido); en forma de un estereoisómero individual o mezcla del mismo, el compuesto libre y/o su sal y/o solvato fisiológicamente aceptable.
ES15737988T 2014-07-15 2015-07-14 Derivados de azaspiro(4,5)decano sustituidos Active ES2680820T3 (es)

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WO2019152688A1 (en) * 2018-01-31 2019-08-08 Aptinyx Inc. Spiro-lactam nmda receptor modulators and uses thereof

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