AR105911A1 - Inhibidores de hdac8 bicíclicos fusionados [6,6] - Google Patents

Inhibidores de hdac8 bicíclicos fusionados [6,6]

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AR105911A1
AR105911A1 ARP160102695A ARP160102695A AR105911A1 AR 105911 A1 AR105911 A1 AR 105911A1 AR P160102695 A ARP160102695 A AR P160102695A AR P160102695 A ARP160102695 A AR P160102695A AR 105911 A1 AR105911 A1 AR 105911A1
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Argentina
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alkyl
heterocycle
cycloalkyl
heteroaryl
aryl
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ARP160102695A
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W Bair Kenneth
Barczak Nicholas
Lancia David Jr
Rudnitskaya Aleksandra
Liu Cuixian
Zablocki Mary
R Margaret - Thomason Jennifer
Han Bingsong
Yee Ng Pui
Zheng Xiaozhang
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Forma Therapeutics Inc
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Publication of AR105911A1 publication Critical patent/AR105911A1/es

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    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
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Abstract

Reivindicación 1: Un compuesto de la fórmula (1), y sus sales, profármacos, solvatos, hidratos, isómeros o tautómeros farmacéuticamente aceptables, en donde: Y¹, Y², Y³ e Y⁴ son cada uno, de modo independiente, N, C o CR³, siempre que, cuando unidos a -C(O)NHOH, cualquiera de Y¹, Y², Y³ o Y⁴ sea C; X se selecciona del grupo que consiste en S(O)₂, S(O), S, O, C(=O) y C(R⁴)(R⁵); W es C(R⁴)(R⁵) u O; R¹ es, de modo independiente, alquilo C₁₋₆, alcoxi C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, cicloalquenilo C₄₋₈, arilo, heteroarilo, heterociclo de 3 a 8 miembros, -(CH₂)ₙ-Rᵃ, -(CH₂)ₙ-O-(CH₂)ₚ-Rᵃ, -S(O)₂Rᵃ, -C(O)Rᵃ, o -C(O)N(Rᵃ)(Rᵇ), en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, arilo, heteroarilo o heterociclo está opcionalmente sustituido con uno o más -OH, halógeno, oxo, -NO₂, -NH₂, -CN, -alquilo C₁₋₆, -alcoxi C₁₋₆, heterociclo, arilo, heteroarilo, o R⁴; Rᵃ es, en cada ocurrencia, hidrógeno, halógeno, OH, NH₂, alquilo C₁₋₆, alcoxi C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, cicloalquenilo C₄₋₈, arilo, heteroarilo, heterociclo de 3 a 8 miembros, o -C(O)N(R¹⁰)(R¹¹), en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, arilo, heteroarilo, o heterociclo es opcionalmente sustituido con uno o más -OH, R⁴’, R⁵’, halógeno, oxo, (CH₂)ₙOR⁶, -NO₂, -OR⁶, -N(R⁶)(R⁷), C(O)OR⁶, -C(O)N(R⁶)(R⁷), -S(O)₂R⁶, -S(O)R⁶, -S(R⁶), -C(O)R⁶, S(O)₂N(R⁶)(R⁷), -CN, alquilo -C₁₋₆, haloalquilo -C₁₋₆, alcoxi -C₁₋₆, alquilamino C₁₋₆, dialquilamino C₁₋₆, hidroxialquilo C₁₋₆, cicloalquilo C₃₋₈, cicloalquilalquilo C₃₋₈, arilalquilo, heterociclo, arilo, o heteroarilo; Rᵇ es, en cada ocurrencia, hidrógeno, halógeno, OH, NH₂, alquilo C₁₋₆, alcoxi C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, cicloalquenilo C₄₋₈, arilo, heteroarilo, heterociclo de 3 a 8 miembros, o -C(O)N(R¹⁰)(R¹¹), en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, arilo, heteroarilo, o heterociclo es opcionalmente sustituido con uno o más -OH, R⁴’, R⁵’, halógeno, oxo, (CH₂)ₙOR⁶, -NO₂, -OR⁶, -N(R⁶)(R⁷), C(O)OR⁶, -C(O)N(R⁶)(R⁷), -S(O)₂R⁶, -S(O)R⁶, -S(R⁶), -C(O)R⁶, -S(O)₂N(R⁶)(R⁷), -CN, alquilo -C₁₋₆, haloalquilo -C₁₋₆, alcoxi -C₁₋₆, alquilamino C₁₋₆, dialquilamino C₁₋₆, hidroxialquilo C₁₋₆, cicloalquilo C₃₋₈, cicloalquilalquilo C₃₋₈, arilalquilo, heterociclo, arilo, o heteroarilo; o Rᵃ y Rᵇ se pueden combinar con el carbono o nitrógeno al que están unidos para formar un cicloalquilo C₃₋₈ o heterociclo de 3 a 8 miembros opcionalmente sustituido con uno o más sustituyentes seleccionados de R⁴’ y R⁵’, en donde R⁴’ y R⁵’ de modo independiente en cada ocurrencia son H o alquilo -C₁₋₆; R² y R²’ son, de modo independiente, hidrógeno, alquilo C₁₋₆, alcoxi C₁₋₆, -OH, halógeno, -NO₂, -NH₂, -CN, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, cicloalquenilo C₄₋₈, arilo, heteroarilo, heterociclo de 3 a 8 miembros, en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, arilo, heteroarilo o heterociclo está opcionalmente sustituido con uno o más -OH, halógeno, oxo, -NO₂, -NH₂, -CN, -alquilo C₁₋₆, -alcoxi C₁₋₆; o R² y R²’ se pueden combinar con el carbono al que están unidos para formar un grupo oxo, cicloalquilo C₃₋₈ o heterociclo de 3 a 8 miembros; R³ es, de modo independiente, en cada aparición, hidrógeno, halógeno, OH, CN, NO₂, NH₂, alquilo C₁₋₃ o alcoxi C₁₋₃; cada R⁴ o R⁵ es cada uno, de modo independiente, en cada aparición, hidrógeno, halógeno, OH, NH₂, alquilo C₁₋₆, alcoxi C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, cicloalquenilo C₄₋₈, arilo, heteroarilo, heterociclo de 3 a 8 miembros o -C(O)N(R¹⁰)(R¹¹), en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, arilo, heteroarilo o heterociclo está opcionalmente sustituido con uno o más -OH, R⁴’, R⁵’, halógeno, oxo, -(CH₂)ₙOR⁶, -NO₂, -OR⁶, -N(R⁶)(R⁷), C(O)OR⁶, -C(O)N(R⁶)(R⁷), -S(O)₂R⁶, -S(O)R⁶, -S(R⁶), -C(O)R⁶, -S(O)₂N(R⁶)(R⁷), -CN, -alquilo C₁₋₆, -haloalquilo C₁₋₆, -alcoxi C₁₋₆, alquil C₁₋₆-amino, dialquil C₁₋₆-amino, hidroxi C₁₋₆-alquilo, cicloalquilo C₃₋₈, cicloalquil C₃₋₈-alquilo, arilalquilo, heterociclo, arilo o heteroarilo; o R⁴ y R⁵ se pueden combinar con el carbono o nitrógeno al que están unidos para formar un grupo oxo, cicloalquilo C₃₋₈ o heterociclo de 3 a 8 miembros, opcionalmente sustituido con uno o más sustituyentes seleccionados de R⁴’ y R⁵’, en donde R⁴’ y R⁵’, de modo independiente, en cada ocurrencia, son H o alquilo -C₁₋₆; o R⁴’ y R⁵’ juntos cuando se unen al mismo átomo forman un anillo spirocicloalquilo C₃₋₈; o R⁴’ y R⁵’ juntos cuando se unen al mismo átomo forman un anillo spiroheterocicloalquilo C₃₋₈; o R⁴’ y R⁵’ juntos cuando se unen a átomos adyacentes forman un anillo arilo, un anillo heteroarilo, un anillo cicloalquilo C₃₋₈, o un heterociclo de 3 a 8 miembros, en donde el spirocicloalquilo, spiroheterocicloalquilo, heteroarilo, cicloalquilo o heterociclo son sustituidos opcionalmente con uno o más grupos seleccionados de OH, halógeno, alquilo -C₁₋₆ o C(O)OR⁶; R⁶ y R⁷ están seleccionados cada uno, de modo independiente, del grupo que consiste en hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, alcoxi C₁₋₆, amino, alquilamino C₁₋₆, dialquilamino C₁₋₆, cicloalquilo C₃₋₈, cicloalquenilo C₃₋₈, arilo, heteroarilo, heterociclo, -S(O)₂NR⁸R⁹, -S(O)₂R⁸, -C(O)R⁸, -CO₂R⁸, -S(O)R⁸ o -S(O)NR⁸R⁹, en donde cada alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, fenilo, heteroarilo o heterociclo está opcionalmente sustituido con uno o más -OH, halógeno, oxo, -NO₂, -NH₂, -CN, -alquilo C₁₋₆, -alcoxi C₁₋₆, alquil C₁₋₆-amino, dialquil C₁₋₆-amino, hidroxi C₁₋₆-alquilo, heterociclo, arilo, heteroarilo; o R⁶ y R⁷ junto con un átomo al que están unidos forman un cicloalquilo C₃₋₈ o un heterociclo de 3 a 8 miembros, en donde el cicloalquilo o el heterociclo es sustituido opcionalmente con uno o más grupos seleccionados de halógeno, oxo y alquilo C₁₋₆; R⁸ y R⁹ son cada uno, de modo independiente, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, cicloalquenilo C₃₋₈, heteroarilo o heterociclo de 3 a 8 miembros, en donde cada uno está opcionalmente sustituido con uno o más -OH, halógeno, oxo, -NO₂, -NH₂, -CN, -alquilo C₁₋₆, -alcoxi C₁₋₆, alquil C₁₋₆-amino, dialquil C₁₋₆-amino, hidroxi C₁₋₆-alquilo, heterociclo, arilo o heteroarilo; R¹⁰ y R¹¹ son cada uno, de modo independiente, hidrógeno, alquilo C₁₋₆, arilo, alquil C₁₋₆-arilo o heterociclo de 3 a 8 miembros; en donde arilo, arilalquilo y heterociclo son sustituidos opcionalmente con uno o más grupos seleccionados de halógeno, alquilo C₁₋₆, y alcoxi C₁₋₆; o R¹⁰ y R¹¹ se pueden combinar para formar un heterociclo de 3 a 8 miembros opcionalmente sustituido con uno o más R¹²; R¹² es H o alquilo C₁₋₆ o dos adyacentes R¹² se pueden combinar para formar un grupo arilo o heteroarilo; n es un número entero de 1 a 6; y p es un número entero de 0 a 2; siempre que el compuesto no sea N-hidroxi-1-((4-metoxifenil)sulfonil)-1,2,3,4-tetrahidroquinolin-6-carboxamida.
ARP160102695A 2015-09-03 2016-09-02 Inhibidores de hdac8 bicíclicos fusionados [6,6] AR105911A1 (es)

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