AR083023A1 - Compuestos de piridina y una composicion farmaceutica que los comprende - Google Patents

Compuestos de piridina y una composicion farmaceutica que los comprende

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Publication number
AR083023A1
AR083023A1 ARP110103396A ARP110103396A AR083023A1 AR 083023 A1 AR083023 A1 AR 083023A1 AR P110103396 A ARP110103396 A AR P110103396A AR P110103396 A ARP110103396 A AR P110103396A AR 083023 A1 AR083023 A1 AR 083023A1
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Argentina
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optionally substituted
alkyl
group
hydrogen
heterocycle
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ARP110103396A
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Purdue Pharma Lp
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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Abstract

Los compuestos de la fórmula (1) sirven para tratar un trastorno sensible al bloqueo de canales de sodio. Los compuestos son especialmente útiles para tratar el dolor, y como neuroprotectores.Reivindicación 1: Un compuesto caracterizado porque tiene la fórmula (1) o una sal, solvato o profármaco de este aceptables desde el punto de vista farmacéutico, en donde Z1 se selecciona del grupo que consiste en N y N-óxido, y Z2 es CR1b; o Z1 es CR1b, y Z2 se selecciona del grupo que consiste en N y N-óxido; R1a y R1b, que son idénticos o diferentes, se seleccionan del grupo que consiste en: hidrógeno; halógeno; hidroxi; ciano; alquilo opcionalmente sustituido; alcoxi; haloalcoxi; y haloalquilo; A1 se selecciona del grupo que consiste en: cicloalquilo opcionalmente sustituido; heterociclo opcionalmente sustituido; arilo opcionalmente sustituido; y heteroarilo opcionalmente sustituido; X se selecciona del grupo que consiste en: -O-; -S-; -SO-; -SO2-; -(CR2R3)j-; -NR4-; y -SO2NH-; en donde: en cada caso, R2 y R3, que son idénticos o diferentes, se seleccionan del grupo que consiste en hidrógeno, flúor y alquilo opcionalmente sustituido; o cada R2 y R3 se toman juntos para formar un grupo oxo; o cada R2 y R3, junto con el átomo de carbono al que están unidos, forman un cicloalquilo opcionalmente sustituido o heterociclo opcionalmente sustituido de 3 a 8 miembros; j es 0, 1, 2 ó 3; y R4 se selecciona del grupo que consiste en hidrógeno y alquilo opcionalmente sustituido; A2 se selecciona del grupo que consiste en arilo opcionalmente sustituido y heteroarilo opcionalmente sustituido; G se selecciona del grupo que consiste en hidrógeno; alquilo; ciano; y los restos de fórmula (G-1) a (G-5); en donde: R5a y R5b, que son idénticos o diferentes, se seleccionan del grupo que consiste en: hidrógeno; alquilo opcionalmente sustituido; cicloalquilo opcionalmente sustituido; heterociclo opcionalmente sustituido; arilo opcionalmente sustituido; heteroarilo opcionalmente sustituido; aralquilo; hidroxialquilo; (ciano)alquilo; (heterociclo)alquilo; (heteroaril)alquilo; (amino)alquilo; (alquilamino)alquilo; (dialquilamino)alquilo; y -(CH2CH2O)m-R15a; o R5a y R5b, junto con el átomo de nitrógeno al que están unidos, forman un heterociclo de 3 a 8 miembros opcionalmente sustituido; R6a y R6b, que son idénticos o diferentes, se seleccionan del grupo que consiste en: hidrógeno; alquilo opcionalmente sustituido; cicloalquilo opcionalmente sustituido; heterociclo opcionalmente sustituido; arilo opcionalmente sustituido; heteroarilo opcionalmente sustituido; hidroxialquilo; (heterociclo)alquilo; (heteroaril)alquilo; (amino)alquilo; (alquilamino)alquilo; (dialquilamino)alquilo; (carboxamido)alquilo; (ciano)alquilo; y (CH2CH2O)n-R15b; R6a y R6b, junto al átomo de nitrógeno al que están unidos, forman un heterociclo de 3 a 8 miembros opcionalmente sustituido; R7 se selecciona del grupo que consiste en: hidrógeno; alquilo opcionalmente sustituido; cicloalquilo opcionalmente sustituido; heterociclo opcionalmente sustituido; arilo opcionalmente sustituido; heteroarilo opcionalmente sustituido; (heterociclo)alquilo; (heteroaril)alquilo; (amino)alquilo; (alquilamino)alquilo; (dialquilamino)alquilo; y (CH2CH2O)o-R15c; R8a y R8b, que son idénticos o diferentes, se seleccionan del grupo que consiste en: hidrógeno; alquilo opcionalmente sustituido; y (CH2CH2O)p-R15d; L se selecciona del grupo que consiste en -O- y -NR16-; R9 se selecciona del grupo que consiste en hidrógeno, alquilo y -(CH2CH2O)q-R15e; R15a, R15b, R15c, R15d y R15e, que son idénticos o diferentes, se seleccionan del grupo que consiste en hidrógeno y alquilo opcionalmente sustituido; R16 se selecciona del grupo que consiste en hidrógeno y alquilo opcionalmente sustituido; m, n, o, p y q son cada uno, independientemente, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 u 11; w es 0, 1, 2, 3, 4 ó 5; x y son cada uno, independientemente, 1, 2, 3, ó 4; E se selecciona del grupo que consiste en hidrógeno; halógeno; alquilo; heteroarilo opcionalmente sustituido; heterociclo opcionalmente sustituido; hidroxialquilo; y los restos de fórmula (E-1) a (E-6); en donde: R17a y R17b, son idénticos o diferentes, se seleccionan del grupo que consiste en: hidrógeno; alquilo opcionalmente sustituido; -SO2R24a; -COR24b; arilo opcionalmente sustituido; heteroarilo opcionalmente sustituido; (heterociclo)alquilo; (heteroaril)alquilo; (amino)alquilo; (alquilamino)alquilo; (dialquilamino)alquilo; (carboxamido)alquilo; (ciano)alquilo; e hidroxialquilo; o R17a y R17b junto con el átomo de nitrógeno al que están unidos, forman un heterociclo de 3 a 8 miembros opcionalmente sustituido; R18a y R18b, que son idénticos o diferentes, se seleccionan del grupo que consiste en: hidrógeno; alquilo opcionalmente sustituido; cicloalquilo opcionalmente sustituido; arilo opcionalmente sustituido; heteroarilo opcionalmente sustituido; (heterociclo)alquilo; (heteroaril)alquilo; y (dialquilamino)alquilo; o R18a y R18b junto con el átomo de nitrógeno al que están unidos, forman un heterociclo de 3 a 8 miembros opcionalmente sustituido; R19 se selecciona del grupo que consiste en hidrógeno y alquilo opcionalmente sustituido; R20a y R20b que son idénticos o diferentes, se seleccionan del grupo que consiste en hidrógeno y alquilo opcionalmente sustituido, en donde al menos uno de R20a y R20b es alquilo opcionalmente sustituido; R21a se selecciona del grupo que consiste en hidrógeno y alquilo; R21b y R21c, que son idénticos o diferentes, se seleccionan del grupo que consiste en: hidrógeno; alquilo opcionalmente sustituido; cicloalquilo opcionalmente sustituido; arilo opcionalmente sustituido; heteroarilo opcionalmente sustituido; (heterociclo)alquilo; (heteroaril)alquilo; y (dialquilamino)alquilo; o R21b y R21c junto con el átomo de nitrógeno al que están unidos, forman un heterociclo de 3 a 8 miembros opcionalmente sustituido; R22 se selecciona del grupo que consiste en hidrógeno y alquilo; R24a se selecciona del grupo que consiste en alquilo opcionalmente sustituido, cicloalquilo opcionalmente sustituido, arilo opcionalmente sustituido y heteroarilo opcionalmente sustituido; R24b se selecciona del grupo que consiste en alquilo opcionalmente sustituido, cicloalquilo opcionalmente sustituido, arilo opcionalmente sustituido y heteroarilo opcionalmente sustituido; t y u son cada uno, independientemente, 0, 1, 2 ó 3; y v es 1, 2 ó 3; en donde: I) G y E no pueden ser ambos hidrógeno; II) cuando G es alquilo, entonces E no es halógeno; III) cuando G es el resto de fórmula (G-1), w es 0, y E es el resto de fórmula (E-1); entonces R17a no es hidrógeno o alquilo cuando R17b es hidrógeno o alquilo; IV) cuando G es el resto de fórmula (G-1), w es 0, y E es el resto de fórmula (E-2), entonces u es 1, 2 ó 3; V) cuando G es el resto de fórmula (G-1), y R5a y R5b, junto con el átomo de nitrógeno al que están unidos, forman un heterociclo de 3 a 8 miembros opcionalmente sustituido, entonces dichos sustituyentes opcionales se seleccionan del grupo que consiste en halo, nitro, ciano, hidroxi, amino, alquilamino, dialquilamino, haloalquilo, hidroxialquilo, alcoxi, haloalcoxi, ariloxi, aralquiloxi, alquiltio, alquilcarbonilo, arilcarbonilo, ureido, guanidino, alquilo opcionalmente sustituido, cicloalquilo opcionalmente sustituido, alquenilo opcionalmente sustituido, alquinilo opcionalmente sustituido, arilo opcionalmente sustituido, heteroarilo opcionalmente sustituido, heterociclo opcionalmente sustituido, alcoxialquilo, (amino)alquilo, hidroxialquilamino, (alquilamino)alquilo, (dialquilamino)alquilo, (ciano)alquilo, (carboxamido)alquilo, mercaptoalquilo, (heterociclo)alquilo y (heteroaril)alquilo; VI) cuando G es el resto de fórmula (G-1) y w es 0, entonces E no es un grupo morfolinilo.
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US20130303526A1 (en) 2013-11-14
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JP2013538227A (ja) 2013-10-10
CN103153955A (zh) 2013-06-12
CA2811479A1 (en) 2012-03-22
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EP2616441B1 (en) 2019-08-07
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