ES2371515T3 - Agonistas del receptor grp119 acoplado a proteína g. piridona. - Google Patents

Agonistas del receptor grp119 acoplado a proteína g. piridona. Download PDF

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ES2371515T3
ES2371515T3 ES08781867T ES08781867T ES2371515T3 ES 2371515 T3 ES2371515 T3 ES 2371515T3 ES 08781867 T ES08781867 T ES 08781867T ES 08781867 T ES08781867 T ES 08781867T ES 2371515 T3 ES2371515 T3 ES 2371515T3
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heterocyclyl
cycloalkyl
aryl
nr14r14
alkyl
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Dean A. Wacker
Karen A. Rossi
Ying Wang
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Bristol Myers Squibb Co
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Abstract

Un compuesto seleccionado entre los compuestos de Fórmula I y Fórmula IA: y enantiómeros, diastereómeros, solvatos y sales farmacéuticamente aceptables de los mismos que tienen un anillo A y un anillo B, en las que: el anillo A está opcionalmente sustituido con uno o más de R mostrados como R20 y R21; G es CH o N; Q es C o N; X es CH o N, con la condición de que Q y X no sean ambos N; Y es CH2, N(R3), C(=O), O, OCR9R9, S, S(=O) o S(O)2; n1 es 0-2; n2 es 0-2; n3 es 1-2; R1 es un arilo monocíclico de 6 miembros, un heteroarilo monocíclico de 5 miembros o un heteroarilo monocíclico de 6 miembros, pudiendo estar cada uno de los mismos opcionalmente sustituido con uno o más miembros seleccionados entre R1a, R1b, R1c, R1d y R1e; cada uno de R1a, R1b, R1c, R1d y R1e se selecciona independientemente entre el grupo que consiste en hidrógeno, alquilo, alquenilo, alquinilo, cicloalquilo, arilo, heterociclilo, halo,- NH2, -CN, -NO2, -C(=O)OH, -C(=O)OR10, -OCF3, -OR11, -OH, -SH, -SR11r S(O)3H, -P(O)3H2, -C(=O)NR9R9, -NR12R12, -S(O)2NR9R9, -NR9S(O)2CF3, - C(=O)NR9S(O)2R9, -S(O)2NR9C(=O)OR9, -S(O)2NR9C(=O)NR9R9, -C(=O)NR9S(O)2CF3, -C(=O)R11, -NR9C(=O)H,- NR9C(=O)R10, -OC(=O)R10, -OC(=O)NR9R9, -C(=NR14)NR9R9, -NHC(=NR14)NR14R14, -S(=O)R11, -S(O)2R11, - NR9C(=O)OR8 y -NR9S(O2)R8, en los que: (a) cada uno de los alquenilo, alquinilo, cicloalquilo, arilo y heterociclilo puede estar opcionalmente sustituido con uno o más de R6; y (b) el alquilo puede estar opcionalmente sustituido con uno o más de R7; R2 es cicloalquilo, arilo, heteroarilo, heterociclilo, -S(O)2R5, -C(=O)NR3R5, -C(=O)R5 o -C(=O)OR5, en el que cada uno de los cicloalquilo, arilo, heteroarilo y heterociclilo puede estar opcionalmente sustituido con uno o más de R6; R3 es hidrógeno, alquilo, alcoxi, cicloalquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, heterociclilo o heterociclilalquilo; R5 es alquilo, alquenilo, arilo, cicloalquilo, heteroarilo o heterociclilo, pudiendo estar cada uno de los mismos opcionalmente sustituido con uno o más de R6; R6, en cada caso, se selecciona independientemente entre alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)OR10, -OCF3, -OR10, -OH, -SH, -SR10, -S(O)3H, -P(O)3H2, -C(=O)NR9R9, -NR9R9, -S(O)2NR9R9, - NR9S(O)2CF3, -C(=O)NR9S(O)2R9, -S(O)2NR9C(=O)OR9, -S(O)2NR9C(=O)NR9R9, -C(=O)NR9S(O)2CF3, - C(=O)R10, -NR9C(=O)H, -NR9C(=O)R10, -OC(=O)R10, -C(=NR14)NR9R9, -NHC(=NR14)NR14R14, -S(=O)R10, - S(O)2R10, =O, -NR9C(=O)OR8 y -NR9S(O2)R8, en el que cada uno de los alquilo, alquenilo, alquinilo, arilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo y heterociclilalquilo puede estar opcionalmente sustituido con 0-5 R9a; R7, en cada caso, se selecciona independientemente entre el grupo que consiste en alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heterociclilo, halo, - NH2, -CN, -NO2, -C(=O)OH, -C(=O)OR10, - OCF3, -OR10, -OH, -SH, -SR10, -S(O)3H, -P(O)3H2, -C(=O)NR9R9, -NR9R9, -S(O)2NR9R9, -NR9S(O)2CF3, - C(=O)NR9S(O)2R9, -S(O)2NR9C(=O)OR9, -S(O)2NR9C(=O)NR9R9, -C(=O)NR9S(O)2CF3, -C(=O)R10,-NR9C(=O)H, - NR9C(=O)R10, -OC(=O)R10, -C(=NR14)NR9R9,- NHC(=NR14)NR14R14, -S(=O)R10, -S(O)2R10, =O, -NR9C(=O)OR8 y -NR9S(O2)R8, en el que cada uno de los alquilo, alquinilo, alquinilo, arilo, cicloalquilo, cicloalquilalquilo y heterociclilo puede estar opcionalmente sustituido con 0-5 R9a; R8, en cada caso, se selecciona independientemente entre el grupo que consiste en alquilo, arilo, cicloalquilo, heteroarilo y heterociclilo, pudiendo estar cada uno de los mismos opcionalmente sustituido con uno o más de R8a; R8a, en cada caso, se selecciona independientemente entre alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)OR14, -OCF3, -OR14, -OH, -SH, -SR14, -S(O)3H, -P(O)3H2, -C(=O)NR14R14, -NR14R14, - S(O)2NR14R14, -NR14S(O)2CF3, -C(=O)NR14S(O)2R14, -S(O)2NR14C(=O)OR14, -S(O)2NR14C(=O)NR14R14, - C(=O)NR14S(O)2CF3, -C(=O)R14, -NR14C(=O)H, -NR14C(=O)R14, -OC(=O)R14, -C(=NR14)NR14R14, -NHC(=NR14) NR14R14, -S(=O)R14, -S(O)2R14, =O, -NR14C(=O)OR14 y -NR14S(O2)R14; R9, en cada caso, se selecciona independientemente entre hidrógeno, alquilo, alcoxi, cicloalquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, heterociclilo y heterociclilalquilo, en el que cada uno de los alquilo, cicloalquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, heterociclilo y heterociclilalquilo puede estar opcionalmente sustituido con 0-5 R9a; R9a, en cada caso, se selecciona independientemente entre alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)OR14, -OCF3, -OR14, -OH, -SH, -SR14, -S(O)3H, -P(O)3H2, -C(=O)NR14R14, -NR14R14, - S(O)2NR14R14, -NR14S(O)2CF3, -C(=O)NR14S(O)2R10, -S(O)2NR14C(=O)OR10, -S(O)2NR14C(=O)NR14R14, - C(=O)NR14S(O)2CF3, -C(=O)R14, -NR14C(=O)H, -NR14C(=O)R14, -OC(=O)R14, -C(=NR14)NR14R14, -NHC(=NR14) NR14R14, -S(=O)R14, -S(O)2R14, -NR14C(=O)OR8, -NR14S(O2)R8, =O y arilalquilo; R10, en cada caso, se selecciona independientemente entre alquilo, alquenilo, alquinilo, cicloalquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, heterociclilo y heterociclilalquilo, en el que cada uno de los cicloalquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, heterociclilo y heterociclilalquilo puede estar opcionalmente sustituido con 0-3 R10a; R10a, en cada caso, se selecciona independientemente entre alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)OR14, -OCF3, -OR14, -OH, -SH, -SR14, -S(O)3H, -P(O)3H2, -C(=O)NR14R14, -NR14R14, S(O)2NR14R14, -NR14S(O)2CF3, -C(=O)NR14S(O)2R9, -S(O)2NR14C(=O)OR9, -S(O)2NR14C(=O)NR14R14, - C(=O)NR14S(O)2CF3, -C(=O)R14, -NR14C(=O)H, -NR14C(=O)R14, -OC(=O)R14, -C(=NR14)NR14R14, - NHC(=NR14)NR14R14, -S(=O)R14, -S(O)2R14, -NR14C(=O)OR8, -NR14S(O2)R8 y arilalquilo; R11, en cada caso, se selecciona independientemente entre alquilo, alquenilo, alquinilo, cicloalquilo, arilo, arilalquilo, heterociclilo y heterociclilalquilo, en el que cada uno de los cicloalquilo, arilo, arilalquilo, heterociclilo y heterociclilalquilo puede estar opcionalmente sustituido con 0-3 R11a; R11a, en cada caso, se selecciona independientemente entre alquilo, haloalquilo, arilo, alquenilo, alquinilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, heterociclilalquilo, halo, -NH2, -CN, -NO2, -C(=O)OH, -C(=O)OR14, -OCF3, -OR14, -OH, -SH, -SR14, -S(O)3H, -P(O)3H2, -C(=O)NR14R14, -NR14R14, - S(O)2NR14R14, -NR14S(O)2CF3, -C(=O)NR14S(O)2R9, -S(O)2NR14C(=O)OR9, -S(O)2NR14C(=O)NR14R14, - C(=O)NR14S(O)2CF3, -C(=O)R14, -NR14C(=O)H, -NR14C(=O)R14, -OC(=O)R14, -C(=NR14)NR14R14, -NHC(=NR14) NR14R14, -S(=O)R14, -S(O)2R14, -NR14C(=O)OR8, -NR14S(O2)R8 y arilalquilo; R12, en cada caso, se selecciona independientemente entre hidrógeno, alquilo, alquenilo, alquinilo, cicloalquilo, arilo, arilalquilo, heterociclilo y heterociclilalquilo, en el que cada uno de los cicloalquilo, arilo, arilalquilo, heterociclilo y heterociclilalquilo puede estar opcionalmente sustituido con 0-3 R10a; R14, en cada caso, se selecciona independientemente entre hidrógeno, alquilo, cicloalquilo y arilo; y cada uno de R20 y R21 se selecciona independientemente entre el grupo que consiste en hidrógeno, alquilo, haloalquilo, cicloalquilo, halo, -CN, -C(=O)OH, -C(=O)OR10, -OCF3, -OR10, -OH, -C(=O)NR9R9, -C(=O)R10 y - OC(=O)R10.
ES08781867T 2007-07-17 2008-07-16 Agonistas del receptor grp119 acoplado a proteína g. piridona. Active ES2371515T3 (es)

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US950162P 2007-07-17

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ES08781867T Active ES2371515T3 (es) 2007-07-17 2008-07-16 Agonistas del receptor grp119 acoplado a proteína g. piridona.
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