ES2855732T3 - Compuestos y composiciones para tratar afecciones asociadas con la actividad de NLRP - Google Patents

Compuestos y composiciones para tratar afecciones asociadas con la actividad de NLRP Download PDF

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ES2855732T3
ES2855732T3 ES17720928T ES17720928T ES2855732T3 ES 2855732 T3 ES2855732 T3 ES 2855732T3 ES 17720928 T ES17720928 T ES 17720928T ES 17720928 T ES17720928 T ES 17720928T ES 2855732 T3 ES2855732 T3 ES 2855732T3
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alkyl
hydroxy
membered
optionally substituted
ring
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Gary Glick
Shomir Ghosh
William R Roush
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Novartis AG
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Novartis AG
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    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings

Abstract

Un compuesto de Fórmula II, **(Ver fórmula)** o una sal farmacéuticamente aceptable del mismo, en donde la Fórmula II se selecciona de **(Ver fórmula)** se selecciona de **(Ver fórmula)** o **(Ver fórmula)** X2 es N o CR9; X3 es NH u O; X3' es O; o cuando X3 es NH, X3 y R2, tomados junto con los átomos que los conectan, forman un anillo heterocíclico de cuatro a siete miembros opcionalmente sustituido con uno o más R16; o cuando X3 es NH, X3 y R4, tomados junto con los átomos que los conectan, forman un anillo heterocíclico de cuatro a siete miembros opcionalmente sustituido con uno o más R16; Y es N o CR8; R8 se selecciona de H, CN, Cl, F, CO2alquilo C1-C6, CO2cicloalquilo C3-C8, CONR11R12, alquilo C1-C6, haloalcoxi C1-C6 y haloalquilo C1-C6; R8' se selecciona de CN, CO2alquilo C1-C6, CO2cicloalquilo C3-C8, CONR11R12 y haloalquilo C1-C6; R9 se selecciona de H, CN, Cl, F, CO2alquilo C1-C6, CO2cicloalquilo C3-C8, CONR11R12, alquilo C1-C6 y haloalquilo C1-C6; R2 es hidrógeno, alcoxi C1-C6, halo, haloalquilo C1-C6 o alquilo C1-C6 opcionalmente sustituido con hidroxi; R2' es hidrógeno, halo o alquilo C1-C6, opcionalmente sustituido con hidroxi; R2" es hidrógeno o alquilo C1-C6; R3 es hidrógeno, CN, alcoxi C1-C6, halo, haloalquilo C1-C6 o alquilo C1-C6 opcionalmente sustituido con hidroxi; R3' es hidrógeno, halo o alquilo C1-C6, opcionalmente sustituido con hidroxi; R3" es hidrógeno, CN o alquilo C1-C6; R4 es hidrógeno, alcoxi C1-C6, halo, haloalquilo C1-C6 o alquilo C1-C6 opcionalmente sustituido con hidroxi; R4' es hidrógeno, halo o alquilo C1-C6, opcionalmente sustituido con hidroxi; R4" es hidrógeno o alquilo C1-C6; R5 es hidrógeno, alcoxi C1-C6, halo, haloalquilo C1-C6 o alquilo C1-C6 opcionalmente sustituido con hidroxi; R5' es hidrógeno, halo o alquilo C1-C6, opcionalmente sustituido con hidroxi; R5" es hidrógeno, CN o alquilo C1-C6; o R2 y R3, tomados junto con los carbonos que los conectan, forman un anillo A de cuatro miembros a siete miembros, o R2' y R3', tomados junto con los carbonos que los conectan, forman un anillo A de cuatro miembros a siete miembros, o R4 y R5, tomados junto con los carbonos que los conectan, forman un anillo B de cuatro miembros a siete miembros, o R4' y R5', tomados junto con los carbonos que los conectan, forman un anillo B de cuatro miembros a siete miembros, o R2 y R3, tomados junto con los carbonos que los conectan, forman un anillo A de cuatro miembros a siete miembros y R4 y R5, tomados junto con los carbonos que los conectan, forman un anillo B de cuatro miembros a siete miembros, o R2' y R3', tomados junto con los carbonos que los conectan, forman un anillo A de cuatro miembros a siete miembros y R4' y R5', tomados junto con los carbonos que los conectan, forman un anillo B de cuatro miembros a siete miembros, en donde anillo A es **(Ver fórmula)** y anillo B es **(Ver fórmula)** en donde anillo A es un anillo carbocíclico saturado; n1 es de 2 a 5; m1 es de 1 a 10; en donde anillo B es un anillo carbocíclico saturado; n2 es de 2 a 5; m2 es de 1 a 10; en donde cada uno de los R6 en cada uno de los anillos es el mismo o diferente y se selecciona de H, alquilo C1-C6, alcoxi C1-C6, NR11R12, oxo y =NR13; o dos R6, tomados junto con el átomo o los átomos que los conectan, forman un anillo carbocíclico de 3 a 8 miembros o heterocíclico saturado que contiene 1 o 2 heteroátomos seleccionados independientemente de O, N, y S; R1 se selecciona de H, alquilo C1-C6 no sustituido, C(R19)2OH, C(O)alquilo C2-C6 y cicloalquilo C3-C6; en donde cada uno de los C(O)alquilo C2-C6 y cicloalquilo C3-C6 anteriores está opcionalmente sustituido con uno o más sustituyentes, cada uno independientemente seleccionado de hidroxi, alcoxi C1-C6, NR11R12, =NR13, COOalquilo C1-C6 y CONR11R12; R1' se selecciona de alquilo C1-C6 no sustituido, C(R19)2OH, C(O)alquilo C2-C6 y cicloalquilo C3-C6; en donde cada uno de los C(O)alquilo C2-C6 y cicloalquilo C3-C6 anteriores está opcionalmente sustituido con uno o más sustituyentes, cada uno independientemente seleccionado de hidroxi, alcoxi C1-C6, NR11R12, =NR13, COOalquilo C1-C6 y CONR11R12; R1" se selecciona de alquilo C1-C6 no sustituido, C(O)alquilo C2-C6 y cicloalquilo C3-C6, en donde cada uno de C(O)alquilo C2-C6 y cicloalquilo C3-C6 anteriores está opcionalmente sustituido con uno o más sustituyentes, cada uno independientemente seleccionado de hidroxi, oxo, alcoxi C1-C6, NR11R12, =NR13, COOalquilo C1-C6 y CONR11R12; R1"' se selecciona de C(R19)2OH; R10 se selecciona de H, Cl, alquilo C1-C6, cicloalquilo C3-C6 y heterocicloalquilo C3-C6, en donde R10 está opcionalmente sustituido con uno o más sustituyentes, cada uno independientemente seleccionado de hidroxi, alcoxi C1-C6, NR11R12, =NR13, COOalquilo C1-C6 y CONR11R12; R10' se selecciona de H, Cl, cicloalquilo C3-C6 y heterocicloalquilo C3-C6; en donde R10' está opcionalmente sustituido con uno o más sustituyentes, cada uno independientemente seleccionado de hidroxi, oxo, alcoxi C1-C6, NR11R12, =NR13, COOalquilo C1-C6 y CONR11R12; R10" se selecciona de Cl, alquilo C1-C6, cicloalquilo C3-C6 y heterocicloalquilo C3-C6; en donde R10" está opcionalmente sustituido con uno o más sustituyentes, cada uno independientemente seleccionado de hidroxi, alcoxi C1-C6, NR11R12, =NR13, COOalquilo C1-C6 y CONR11R12; R10"' se selecciona de Cl, alquilo C1-C6 sustituido con hidroxi, cicloalquilo C3-C6 y heterocicloalquilo C3-C6; en donde los cicloalquilo C3-C6 y heterocicloalquilo C3-C6 anteriores está opcionalmente sustituido con uno o más sustituyentes, cada uno independientemente seleccionado de hidroxi, oxo, alcoxi C1-C6, NR11R12, =NR13, COOalquilo C1- C6 y CONR11R12; o R1 y R10, tomados junto con los átomos que los conectan, forman un anillo carbocíclico o heterocíclico de 3 a 8 miembros que contiene 1 o 2 heteroátomos seleccionados independientemente de O, N y S, en donde el anillo está opcionalmente sustituido con uno o más sustituyentes, seleccionados cada uno independientemente de hidroxi, oxo, alcoxi C1-C6, NR11R12, =NR13, COOalquilo C1-C6 y CONR11R12; R13 es alquilo C1-C6; cada uno de los R11 y R12, en cada aparición, se selecciona independientemente de hidrógeno, alquilo C1-C6, CO2R15 y CONR17R18; R15 es alquilo C1-C6; cada uno de R17 y R18 en cada aparición se selecciona independientemente de hidrógeno y alquilo C1-C6; cada uno de los R16 es el mismo o diferente y se selecciona de H, alquilo C1-C6, alcoxi C1-C6, NR11R12, oxo y =NR13; cada uno de los R19 es el mismo y es alquilo C1-C6. R20 se selecciona de H, halo o alquilo C1-C6, opcionalmente sustituido con hidroxi; R21 se selecciona de H, halo o alquilo C1-C6 sustituido con hidroxi; con la condición de que si (1) en la Fórmula II es **(Ver fórmula)** y si (2) R10' es H o heterociclilo C3-C6, entonces **(Ver fórmula)** no es **(Ver fórmula)** y con la condición de que si: (1) Fórmula II es **(Ver fórmula)** o **(Ver fórmula)** y (2) cualquiera de R1 o R1', cuando está presente, es C(R19)2OH; y (3) cualquiera de R10' o R10"', cuando está presente, no es Cl; entonces **(Ver fórmula)** no es **(Ver fórmula)** y con la condición de que si: (1) Fórmula II es **(Ver fórmula)** y (2) R10'" es alquilo C1-C6 sustituido con hidroxi; entonces **(Ver fórmula)** no es **(Ver fórmula)**
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