AR088611A1 - Derivados de quinolina carboxamida y quinolina carbonitrilo como moduladores alostericos negativos de mglur2, composiciones, y su uso - Google Patents

Derivados de quinolina carboxamida y quinolina carbonitrilo como moduladores alostericos negativos de mglur2, composiciones, y su uso

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AR088611A1
AR088611A1 ARP120104094A ARP120104094A AR088611A1 AR 088611 A1 AR088611 A1 AR 088611A1 AR P120104094 A ARP120104094 A AR P120104094A AR P120104094 A ARP120104094 A AR P120104094A AR 088611 A1 AR088611 A1 AR 088611A1
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Argentina
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alkyl
group
phenyl
cycloalkyl
independently selected
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ARP120104094A
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Merck Sharp & Dohme
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Abstract

Reivindicación 1: Un compuesto de fórmula (1) o un estereoisómero del mismo, o una sal farmacéuticamente aceptable de dicho compuesto o dicho estereoisómero, en la que: el anillo A es un resto seleccionado entre el grupo que consiste en: fenilo, -cicloalquilo C₅₋₆, -cicloalquenilo C₅₋₆, -piridinilo, pirimidinilo, -pirazolilo, -tienilo, -tiazolilo, -tiadiazolilo, y -oxazolilo; RQ se selecciona entre el grupo que consiste en -CN y -C(O)NH₂; -L- es un enlace o resto divalente seleccionado entre el grupo que consiste en: -(C(R¹L)₂)ₚ-, un resto de fórmula (2), -C(O)-, -S(O)- y -S(O)₂-; p es 1, 2 ó 3; cada R¹L se selecciona independientemente entre el grupo que consiste en H, -CH₃, -CF₃, -OH, -C(O)-, halógeno, -ciclopropilo, -O-CH₃, y -O-CF₃; R¹ se selecciona entre el grupo que consiste en: {1} heterocicloalquilo y heterocicloalquenilo, en el que dicho heterocicloalquilo y dicho heterocicloalquenilo son sistemas anulares monocíclicos o multicíclicos que comprenden de 3 a 10 átomos en el anillo en los que 1, 2 ó 3 de los átomos de cada uno de dichos sistemas anulares es un heteroátomo en el anillo seleccionado independientemente entre el grupo que consiste en N, S, S(O), S(O)₂, y O, y en el que cada uno de dichos grupos heterocicloalquilo y cada uno de dichos grupos heterocicloalquenilo están sin sustituir o sustituidos con 1 a 5 grupos seleccionados independientemente entre el grupo que consiste en oxo, CN, -OH, halógeno, -alquilo C₁₋₆, -alquilo C₁₋₆ hidroxisustituido, -alquinilo C₁₋₆, -haloalquilo C₁₋₆, -haloalquilo C₁₋₆ hidroxisustituido, -O-alquilo C₁₋₆, -cicloalquilo C₃₋₈, -alquil-cicloalquilo, -CH(OH)cicloalquilo, fenilo, -alquil-fenilo, heteroarilo monocíclico, -alquil-heteroarilo monocíclico, -espirocicloalquilo C₃₋₈, -espiroheterocicloalquilo C₃₋₈, -C(O)H, -C(O)OH, -C(O)alquilo C₁₋₆, -C(O)O-alquilo C₁₋₆, -N(R¹A)C(O)alquilo C₁₋₆, -N(R¹A)₂, -C(O)N(R¹A)₂, -S(O)₂H, -S(O)-fenilo, -S(O)-alquil C₁₋₆-fenilo, -S(O)₂-fenilo, -S(O)₂-alquil C₁₋₆-fenilo, -S(O)₂OH, y -S(O)₂-alquilo C₁₋₆, en el que cada grupo R¹A se selecciona independientemente entre el grupo que consiste en H y -(alquilo C₁₋₆); {2} heteroarilo, en el que dicho heteroarilo es un sistema anular monocíclico o multicíclico que comprende de 5 a 10 átomos en el anillo en el que de 1 a 4 de los átomos de dicho sistema anular es un átomo de nitrógeno en el anillo, y en el que dicho heteroarilo está sin sustituir o sustituido con 1 a 5 grupos seleccionados independientemente entre el grupo que consiste en oxo, CN, -OH, halógeno, -alquilo C₁₋₆, -alquilo C₁₋₆ hidroxisustituido, -alquinilo C₁₋₆, -haloalquilo C₁₋₆, -haloalquilo C₁₋₆ hidroxisustituido, -O-alquilo C₁₋₆, -cicloalquilo C₃₋₈, -alquil-cicloalquilo, -CH(OH)cicloalquilo, fenilo, -alquil-fenilo, heteroarilo monocíclico, -alquil-heteroarilo monocíclico, -espirocicloalquilo C₃₋₈, -C(O)H, -C(O)OH, -C(O)alquilo C₁₋₆, -C(O)O-alquilo C₁₋₆, -N(R¹B)C(O)alquilo C₁₋₆, -N(R¹B)₂, -C(O)N(R¹B)₂, -S(O)₂H, -S(O)-fenilo, -S(O)-alquil C₁₋₆-fenilo, -S(O)₂-fenilo, -S(O)₂-alquil C₁₋₆-fenilo, -S(O)₂OH, y -S(O)₂-alquilo C₁₋₆, en el que cada grupo R¹B se selecciona independientemente entre el grupo que consiste en H y -(alquilo C₁₋₆), con la condición de que R¹ no sea triazolilo sin sustituir o sustituido, y con la condición adicional de que cuando R¹ es oxadiazolilo sustituido, tiazolilo sustituido, o tiadiazolilo sustituido, entonces -L- se selecciona entre el grupo que consiste en -(C(R¹L)₂)ₚ-, y el resto de fórmula (2); {3} fenilo, en el que dicho fenilo está sin sustituir o sustituido con 1 a 5 grupos seleccionados independientemente entre el grupo que consiste en oxo, CN, -OH, halógeno, -alquilo C₁₋₆, -alquinilo C₁₋₆, -haloalquilo C₁₋₆, -O-alquilo C₁₋₆, -cicloalquilo C₃₋₈, -alquil-cicloalquilo -CH(OH)cicloalquilo, heteroarilo monocíclico, -alquil-heteroarilo monocíclico, -espirocicloalquilo C₃₋₈, -C(O)H, -C(O)OH, -C(O)alquilo C₁₋₆, -C(O)O-alquilo C₁₋₆, N(R¹C)C(O)alquilo C₁₋₆, -N(R¹C)₂, -C(O)N(R¹C)₂, -S(O)₂H, -S(O)-fenilo, -S(O)-alquil C₁₋₆-fenilo, -S(O)₂-fenilo, -S(O)₂-alquil C₁₋₆-fenilo, -S(O)₂OH, y -S(O)₂-alquilo C₁₋₆, en el que cada grupo R¹C se selecciona independientemente entre el grupo que consiste en H y -(alquilo C₁₋₆); {4} H y -alquilo C₁₋₆; {5} -CH₂N(R¹D)R¹E, en el que: R¹D se selecciona entre el grupo que consiste en H, -alquilo C₁₋₆, y -C(O)OR¹H; y R¹E se selecciona entre el grupo que consiste en -O-alquilo C₁₋₆, heteroalquilo, -alquil-C(O)N(R¹H), y -C(O)OR¹H, en el que cada R¹H se selecciona independientemente entre el grupo que consiste en H y -alquilo C₁₋₆; y {6} -CH₂N(R¹F)OR¹G, en el que: R¹F se selecciona entre el grupo que consiste en H, -alquilo C₁₋₆, y -C(O)OR¹H, en el que cada R¹H se selecciona independientemente entre el grupo que consiste en H y -alquilo C₁₋₆; y R¹G se selecciona entre el grupo que consiste en H y -alquilo C₁₋₆; n es 0, 1, 2 ó 3; cada R² (cuando está presente) se selecciona independientemente entre el grupo que consiste en halógeno, -CN, -OH, -alquilo C₁₋₆, -O-alquilo C₁₋₆, -haloalquilo C₁₋₆, -O-haloalquilo C₁₋₆, ciclopropilo, ciclobutilo, ciclopentilo, ciclohexilo, -NH₂, -NH-alquilo C₁₋₆, -N(alquil C₁₋₆)₂, -C(O)O-alquilo C₁₋₆, y fenilo; y R³ se selecciona entre el grupo que consiste en hidrógeno y flúor.
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