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AR061886A1 - Compuestos derivados de 3-oxo-isoindolina-1-carboxamida, composicion farmaceutica y uso - Google Patents

Compuestos derivados de 3-oxo-isoindolina-1-carboxamida, composicion farmaceutica y uso

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Publication number
AR061886A1
AR061886A1 ARP070103082A ARP070103082A AR061886A1 AR 061886 A1 AR061886 A1 AR 061886A1 AR P070103082 A ARP070103082 A AR P070103082A AR P070103082 A ARP070103082 A AR P070103082A AR 061886 A1 AR061886 A1 AR 061886A1
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Argentina
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aryl
alkyl
halogen
cyano
optionally substituted
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ARP070103082A
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Astrazeneca Ab
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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Abstract

Los compuestos de la presente son de utilidad en la profilaxis y en el tratamiento de las arritmias, en particular las arritmias auriculares y ventriculares. Reivindicacion 1: Un compuesto de la formula (1) en la cual R1 representa alquilo C1-12 (grupo alquilo que está optativamente sustituido o fusionado con uno o más grupos seleccionados entre halogeno, alquenilo C2-6, cicloalquilo C3-8, ciano, oxo, -OR8, -COR9, -SR10, -COXR11, -N(R12a)(R12b), -N(R13a)C(O)OR13b, -OC(O)N(R14a)(R14b), - SO2R15, arilo o Het1); además, R1 representa cicloalquilo C3-8, arilo o Het2; R8 a R11, R13a, R13b, R15 representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het9 (grupos alquilo C1-6, arilo y Het9 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het10); R12a y R12b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het11 (grupos alquilo C1-6, arilo y Het11 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het12), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R14a y R14b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het13 (grupos alquilo C1-6, arilo y Het13 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het14), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R2 representa alquilo C1-12 (grupo alquilo que está optativamente sustituido con uno o más grupos seleccionados entre halogeno, -OR16, -COR17, alquenilo C2-6, cicloalquilo C3-8, ciano, trialquilsililo, -COXR18, arilo o Het3); además, R2 representa (CH2)kN(R19a)(R19b), -(CH2)kNR20aC(O)N(R20b)(R20c), -(CH2)nNR21aSO2R21b, -(CH2)nSO2R22, -(CH2)kN(R23a)C(O)OR23b, -OC(O)N(R24a)(R24b), cicloalquilo C3-8, arilo o Het4; R16 a R18, R21, R22, R23a, R23b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het15 (grupos alquilo C1-6, arilo y Het15 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het16); R19a y R19b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het19 (grupos alquilo C1-6, arilo y Het19 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het20) o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R20a, R20b y R20c representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het21 (grupos alquilo C1-6, arilo y Het21 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het22); R20b y R20c juntos, pueden representar alquileno C3-6, optativamente interrumpido por un átomo de O; R3 representa hidrogeno, alquilo C1-12 (grupo alquilo que está optativamente sustituido con uno o más grupos seleccionados entre halogeno, -OR25, -COR26, alquenilo C2- 6, cicloalquilo C3-8, trialquilsililo,-COXR27, arilo o Het5); además R3 representa (CH2)kN(R28a)(R28b), -(CH2)kN(R29a)C(O)N(R29b)(R29c), -(CH2)nNR30aSO2R30b, -(CH2)nSO2R31, -(CH2)kN(R32a)C(O)OR32b, OC(O)N(R33a)(R33b), cicloalquilo C3-8, arilo o Het6; R25 a R27, R30, R31, R32a, R32b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het23 (grupos alquilo C1-6, arilo y Het23 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het24); R28a y R28b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het25 (grupos alquilo C1-6, arilo y Het25 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het26), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R33a y R33b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het27 (grupos alquilo C1-6, arilo y Het27 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het28) o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R29a, R29b, y R29c representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het29 (grupos alquilo C1-6, arilo y Het29 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het30); R29b y R29c juntos pueden representar alquileno C3-6, optativamente interrumpido por un átomo de O; R4 representa hidrogeno, -OH, arilo, alquilo C1-6 (grupo alquilo que está optativamente sustituido con uno o más grupos seleccionados entre halogeno, hidroxi, alquenilo C2-4, trialquilsililo), -OR34, -(CH2)mR35; R34 representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het31 (grupos alquilo C1-6, arilo y Het31 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het32); R35 representa independientemente arilo o Het33 (grupos arilo y Het33 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het34); R5 a R7 representan independientemente, en cada caso, hidrogeno, -OH, halogeno, ciano, nitro, alquilo C1-6, -OR36, - N(R37a)(R37b), -C(O)R38, -C(O)OR39, -C(O)N(R40a)(R40b), -NC(O)OR41, -OC(O)N(R42a)(R42b), -N(R43a)C(O)R43b, -N(R44a)S(O)2R44b, -S(O)2R45, -OS(O)2R46, -(CH2)nN(R47a)(R47b), -(CH2)nNR48aC(O)N(R48b)(R48c), -(CH2)nNR49aSO2R49b, trialquilsililo, arilo o Het7; R36, R38, R39, R41, R43, R44a, R44b, R45, R46, R49a y R49b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het35 (grupos alquilo C1-6, arilo y Het35 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het36); R37a y R37b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het37 (grupos alquilo C1-6, arilo y Het37 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het38), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R40a y R40b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het39 (grupos alquilo C1-6, arilo y Het39 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het40), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R42a y R42b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het41 (grupos alquilo C1-6, arilo y Het41 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het42), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R47a y R47b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het43 (grupos alquilo C1-6, arilo y Het43 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het44), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R48a, R48b y R48c representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het45 (grupos alquilo C1-6, arilo y Het45 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het46); R48b y R48c juntos pueden representar alquileno C3-6, optativamente interrumpido por un átomo de O; arilo está, encada caso, optativamente sustituido con -OH, halogeno, ciano, nitro, alquilo C1-6, cicloalquilo C3-8, alquenilo C2-6, arilo, Het8, -OR50, -(CH2)mR51, -SR52, -C(O)R53, -COXR54, -N(R55a)(R55b), -SO2R56, -OS(O)2R57, -(CH2)mN(R58a)(R58b), -(CH2)mNR59aC(O)N(R59b)(R59c), -C(O)OR60, -C(O)N(R61a)(R61b), -N(R62a)C(O)R62b, - N(R63a)C(O)OR63b, -OC(O)N(R64a)(R64b), -N(R65a)S(O)2R65b y OC(O)R66; R50 a R54, R56, R57, R60, R62a, R62b, R63a, R63b, R65a, R65b y R66 representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het47 (grupos alquilo C1-6, arilo y Het47 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het48); R51 representa independientemente arilo o Het49 (grupos arilo y Het49 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het50); R55a y R55b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het51 (grupos alquilo C1-6, arilo y Het51 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het52), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R58a y R58b representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het53 (grupos alquilo C1-6, arilo y Het53 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het54), o juntos representan alquileno C3-6, optativamente interrumpido por un átomo de O; R59a, representan independientemente, en cada caso, hidrogeno, alquilo C1-6, arilo o Het55 (grupos alquilo C1-6, arilo y Het55 que están optativamente sustituidos con uno o más sustituyentes seleccionados entre -OH, halogeno, ciano, nitro, alquilo C1-6, arilo y Het56); R59b y R59c juntos p
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