ES2319886T3 - Compuestos azabiciclicos condensados que inhiben el sutipo 1 del receptor valinoide (vr1). - Google Patents

Compuestos azabiciclicos condensados que inhiben el sutipo 1 del receptor valinoide (vr1). Download PDF

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ES2319886T3
ES2319886T3 ES03716014T ES03716014T ES2319886T3 ES 2319886 T3 ES2319886 T3 ES 2319886T3 ES 03716014 T ES03716014 T ES 03716014T ES 03716014 T ES03716014 T ES 03716014T ES 2319886 T3 ES2319886 T3 ES 2319886T3
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compounds
valinoid
sutipo
azabiciclic
condensed
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Chih-Hung Lee
Erol K. Bayburt
Stanley Didomenico Jr.
Irene Drizin
Arthur R. Gomtsyan
John R. Koenig
Richard J. Perner
Robert G. Schmidt
Sean C. Turner
Tammie K. White
Guo Zhu Zheng
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Abbott Laboratories
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Abbott Laboratories
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Abstract

Un compuesto de fórmula (I) ** ver fórmula** o una sal farmacéuticamente aceptable del mismo, donde --- está ausente o es un enlace sencillo X1, es CR1 X2 se selecciona entre el grupo que consiste en N y CR2; X 3 se selecciona entre el grupo que consiste en N, NR 3 y CR 3; X4 es un enlace o se selecciona entre el grupo que consiste en N y CR4; X 5 se selecciona entre el grupo que consiste en N y C; con la condición de que al menos uno de X2, X3 y X4 sea N; Z 1 es O; Z2 es un enlace o se selecciona entre el grupo que consiste en NH y O; L se selecciona entre el grupo que consiste en alquenileno, alquileno, alquinileno, cicloalquileno y -(CH 2) mO (CH 2) n-, donde el extremo izquierdo de -(CH 2) mO(CH 2) n- está unido a Z 2 y el extremo derecho esta unido a R 9; cada uno de m y n es independientemente 0-6; cada uno de R 1, R 3, R 5, R 6 y R 7 se selecciona independientemente entre el grupo que consiste en hidrógeno, alquenilo, alcoxi, alcoxialcoxi, alcoxialquilo, alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilo, alquilcarbonilalquilo, alquilcarboniloxi, alquiltio, alquinilo, carboxi, carboxialquilo, ciano, cianoalquilo, cicloalquilo, cicloalquilalquilo, formilo, formilalquilo, haloalcoxi, haloalquilo, haloalquiltio, halógeno, hidroxi, hidroxialquilo, mercapto, mercaptoalquilo, nitro, (CF 3) 2(HO)C-, -NR AS(O) 2R B, -S(O) 2OR A, -S(O) 2R B, -NZ AZ B, (NZ AZ B)alquilo, (NZ AZ B)carbonilo, (NZ AZ B)carbonilalquilo y (NZ AZ B)sulfonilo, donde cada uno de Z A y Z B se selecciona independientemente entre el grupo que consiste en hidrógeno, alquilo, alquilcarbonilo, formilo, arilo y arilalquilo; cada uno de R2 y R4 se selecciona independientemente entre el grupo que consiste en hidrógeno, alquenilo, alcoxi, alcoxialcoxi, alcoxialquilo, alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilo, alquilcarbonilalquilo, alquilcarboniloxi, alquiltio, alquinilo, carboxi, carboxialquilo, ciano, cianoalquilo, cicloalquilo, cicloalquilalquilo, formilo, formilalquilo, haloalcoxi, haloalquilo, haloalquiltio, halógeno, hidroxi, hidroxialquilo, mercapto, mercaptoalquilo, nitro, (CF3)2(HO)C-, -NRAS(O)2RB, -S(O)2ORA, -S(O)2RB, -NZAZB, (NZAZB)alquilo, (NZAZB)alquilcarbonilo, (NZAZB)carbonilo, (NZAZB)carbonilalquilo, (NZAZB)sulfonilo, (NZAZB)C(=NH)-, (NZAZB)C(=NCN)NH- y (NZAZB) C(=NH)NH-; RA se selecciona entre el grupo que consiste en hidrógeno y alquilo; RB se selecciona entre el grupo que consiste en alquilo, arilo y arilalquilo; R8a se selecciona entre el grupo que consiste en hidrógeno y alquilo; R8b está ausente cuando X5 es N o R8b se selecciona entre el grupo que consiste en hidrógeno, alcoxi, alcoxicarbonilalquilo, alquilo, alquilcarboniloxi, alquilsulfoniloxi, halógeno e hidroxi cuando X 5 es C; y R9 se selecciona entre el grupo que consiste en hidrógeno, arilo, cicloalquilo y heterociclo; donde el arilo por sí solo o como parte de otro grupo es un grupo fenilo, o un sistema de anillos condensados, bicíclicos o tricíclicos, donde uno o más de los anillos condensados es un grupo fenilo, estando dicho arilo opcionalmente sustituido con 1, 2, 3, 4 ó 5 sustituyentes seleccionados independientemente entre alquenilo, alcoxi, alcoxialcoxi, alcoxialquilo, alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilo, alquilcarbonilalquilo, alquilcarboniloxi, alquilsulfonilo, alquiltio, alquinilo, carboxi, carboxi-alquilo, ciano, cianoalquilo, cicloalquilo, cicloalquilalquilo, etilendioxi, formilo, formilalquilo, haloalcoxi, haloalquilo, haloalquiltio, halógeno, hidroxi, hidroxialquilo, metilendioxi, mercapto, mercaptoalquilo, nitro, -NZ CZ D, (NZ CZ D) alquilo, (NZ CZ D)carbonilo, (NZ CZ D)carbonilalquilo, (NZ CZ D)sulfonilo, -NRAS(O)2RB, -S(O)2ORA y -S(O)2RA donde RA y RB son independientemente como se han definido anteriormente y ZC y ZD se seleccionan independientemente entre el grupo que consiste en hidrógeno, alquilo, alquilcarbonilo, formilo, arilo y arilalquilo, estando dicho arilo opcionalmente sustituido adicionalmente con uno cualquiera de un grupo arilo, arilalquilo, ariloxi, ariltio, heterociclo, heterociclo alquilo, heterociclooxi o heterociclotio adicional, donde el grupo arilo, arilalquilo, ariloxi, ariltio, heterociclo, heterocicloalquilo, heterociclooxi y heterociclotio adicional puede estar sustituido con 1, 2, 3, 4 ó 5 sustituyentes seleccionados independientemente entre alquenilo, alcoxi, alcoxialcoxi, alcoxialquilo, alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilo, alquilcarbonilalquilo, alquilcarboniloxi, alquilsulfonilo, alquiltio, alquinilo, carboxi, carboxialquilo, ciano, cianoalquilo, cicloalquilo, cicloalquilalquilo, formilo, formilalquilo, haloalcoxi, haloalquilo, haloalquiltio, halógeno, hidroxi, hidroxialquilo, mercapto, mercaptoalquilo, nitro, -NZCZD, (NZCZD)alquilo, (NZCZD)carbonilo, (NZCZD)carbonilalquilo, (NZCZD)sulfonilo, -NRAS(O)2RB, -S(O)2 ORA y -S(O)2RA donde RA y RB son independientemente como se han definido anteriormente y ZC y ZD se seleccionan independientemente entre el grupo que consiste en hidrógeno, alquilo, alquilcarbonilo, formilo, arilo y arilalquilo; heterociclo por sí solo o como parte de otro grupo es un sistema de anillos monocíclicos, bicíclicos o tricíclicos, estando dicho heterociclo opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente entre alquenilo, alcoxi, alcoxialcoxi, alcoxialquilo, alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilo, alquilcarbonilalquilo, alquilcarboniloxi, alquilsulfonilo, alquiltio, alquinilo, arilalquilo, ariloxi, ariltio, carboxi, carboxialquilo, ciano, cianoalquilo, cicloalquilo, cicloalquilalquilo, formilo, formilalquilo, haloalcoxi, haloalquilo, haloalquiltio, halógeno, hidroxi, hidroxialquilo, mercapto, mercaptoalquilo, nitro, oxo, -NZCZD, (NZCZD)alquilo, (NZCZD) carbonilo, (NZCZD)carbonilalquilo, (NZCZD)sulfonilo, -NRAS(O)2RB, -S(O)2ORA y -S(O)2RA donde RA y RB son independientemente como se han definido anteriormente y ZC y ZD se seleccionan independientemente entre el grupo que consiste en hidrógeno, alquilo, alquilcarbonilo, formilo, arilo y arilalquilo, estando dicho heterociclo opcionalmente sustituido adicionalmente con uno cualquiera de un grupo arilo, arilalquilo, ariloxi, ariltio, heterociclo, heterociclo alquilo, heterociclooxi o heterociclotio adicional, donde el grupo arilo, arilalquilo, ariloxi, ariltio, heterociclo, heterocicloalquilo, heterociclooxi y heterociclotio adicional puede estar sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente entre alquenilo, alcoxi, alcoxialcoxi, alcoxialquilo; alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilo, alquilcarbonilalquilo, alquilcarboniloxi, alquilsulfonilo, alquiltio, alquinilo, carboxi, carboxialquilo, ciano, cianoalquilo, cicloalquilo, cicloalquilalquilo, etilendioxi, formilo, formilalquilo, haloalcoxi, haloalquilo, haloalquiltio, halógeno, hidroxi, hidroxialquilo, mercapto, mercaptoalquilo, nitro, -NZCZD, (NZCZD)alquilo, (NZCZD) carbonilo, (NZCZD)carbonilalquilo, (NZCZD)sulfonilo, -NRAS(O)2RB, -S(O)2ORA y -S(O)2RA donde RA y RB son independientemente como se han definido anteriormente y Z C y Z D se seleccionan independientemente entre el grupo que consiste en hidrógeno, alquilo, alquilcarbonilo, formilo, arilo y arilalquilo; cicloalquilo por sí solo o como parte de otro grupo es un sistema de anillos monocíclicos, bicíclicos o tricíclicos, estando dicho cicloalquilo opcionalmente sustituido con 1, 2, 3, 4 ó 5 sustituyentes seleccionados independientemente entre alquenilo, alcoxi, alcoxialcoxi, alcoxialquilo, alcoxicarbonilo, alcoxicarbonilalquilo, alquilo, alquilcarbonilo, alquilcarbonilalquilo, alquilcarboniloxi, alquilsulfonilo, alquiltio, alquinilo, carboxi, carboxialquilo, ciano, cianoalquilo, formilo, haloalcoxi, haloalquilo, haloalquiltio, halógeno, hidroxi, hidroxialquilo, mercapto, mercaptoalquilo, nitro, -NZCZD, (NZCZD)alquilo, (NZCZD)carbonilo, (NZCZD)carbonilalquilo, (NZCZD)sulfonilo, -NRAS(O)2RB -S(O)2ORAy -S(O) 2R A donde R A y R B son independientemente como se han definido anteriormente y Z C y Z D se seleccionan independientemente entre el grupo que consiste en hidrógeno, alquilo, alquilcarbonilo, formilo, arilo y arilalquilo; alquilo por sí solo o como parte de otro grupo es un alquilo C1-C10; alquenilo por sí solo o como parte de otro grupo es un alquenilo C 2-C 10; alquinilo por sí solo o como parte de otro grupo es un alquinilo C2-C10; con la condición de que se excluyan 5-acetamidoisoquinolina; isoquinolina-5-carbamato de metilo; isoquinolina-5-carbamato de etilo; 5-acetamido-6-nitro-isoquinolina; 5-acetamido-6-amino-isoquinolina; 5-acetilamino-7-amino-8-hidroxiisoquinolina; 5-acetilamino-7-amino-isoquinolina; 5-acetamido-8-nitro-isoquinolina; 5-acetamido-8-amino-isoquinolina; 5-acetamido-1-metilisoquinolina; 5-N-metilacetamido-1-metilisoquinolina; 5-N-etilacetamido-1-metilisoquinolina; 5-N-metilacetamido-1-formilisoquinolina; 5-N-etilacetamido-1-formilisoquinolina; indolo-4-N-etilacetamida; y indolo-4-N-propilacetamida.
ES03716014T 2002-02-20 2003-02-11 Compuestos azabiciclicos condensados que inhiben el sutipo 1 del receptor valinoide (vr1). Expired - Lifetime ES2319886T3 (es)

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