AR110590A1 - Activador de nrf2 - Google Patents
Activador de nrf2Info
- Publication number
- AR110590A1 AR110590A1 ARP170103684A ARP170103684A AR110590A1 AR 110590 A1 AR110590 A1 AR 110590A1 AR P170103684 A ARP170103684 A AR P170103684A AR P170103684 A ARP170103684 A AR P170103684A AR 110590 A1 AR110590 A1 AR 110590A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- membered
- alkynyl
- alkenyl
- carbocyclyl
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/47—Quinolines; Isoquinolines
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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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- C07D217/08—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with a hetero atom directly attached to the ring nitrogen atom
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- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
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- C07D223/16—Benzazepines; Hydrogenated benzazepines
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- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
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- C07D405/06—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 carbon chain containing only aliphatic carbon atoms
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- C07D498/14—Ortho-condensed systems
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Abstract
Se proporcionan compuestos, sales farmacéuticamente aceptables de estos, métodos para su uso y producción. Reivindicación 1: Un compuesto representado por la fórmula (1), o una sal farmacéuticamente aceptable de este, donde R¹ es -CN, -C(O)Rᵃ, CH₃S(O)₂- o alquilo C₁₋₈ sustituido con uno o más átomos de flúor; Rᵃ es H, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, -OR¹¹, -SR¹⁴, -N(R¹²)₂, -NR¹³OR¹³, -NR¹³S(O)₂R¹³, -NR¹³C(O)R¹³, -N(R¹³)N(R¹³)₂, -N(R¹³)C(O)OR¹³ o -N(R¹³)C(O)N(R¹³)₂, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, el carbociclilo de 3 a 12 miembros y el heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más de R²¹; R² es H, halo, -NO₂, -CN, -N₃, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, -C(O)R¹³, -C(S)R¹³, -C(O)OR¹³, -C(S)SR¹³, -C(O)SR¹³, -C(S)OR¹³, -SC(O)R¹³, -OC(S)R¹³, -SC(S)R¹³, -C(O)N(R¹³)₂, -OR¹¹, -SR¹⁴, -N(R¹²)₂, -N(R¹³)OR¹³, -N(R¹³)S(O)₂R¹³, -N(R¹³)C(O)R¹³, -N(R¹³)N(R¹³)₂, -N(R¹³)C(O)OR¹³, -N(R¹³)C(O)N(R¹³)₂, -S(O)₂R¹³, -S(O)R¹³, -S(O)N(R¹³)₂, -S(O)₂N(R¹³)₂, N⁺(R¹³)₃, -S⁺(R¹³)₂ o -Si(R¹³)₃, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; R³ᵃ es H, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, -C(O)R¹³, -C(O)OR¹³, -C(O)N(R¹³)₂, -OR¹¹, -N(R¹²)₂, -N(R¹³)OR¹³, -N(R¹³)S(O)₂R¹³, -N(R¹³)C(O)R¹³, -N(R¹³)N(R¹³)₂, -N(R¹³)C(O)OR¹³, -N(R¹³)C(O)N(R¹³)₂, -S(O)R¹³, -S(O)N(R¹³)₂ o -S(O)₂N(R¹³)₂, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; y R³ᵇ es alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, -C(O)R¹³, -C(O)OR¹³, -C(O)N(R¹³)₂, -OR¹¹, -N(R¹²)₂, -N(R¹³)OR¹³, -N(R¹³)S(O)₂R¹³, -N(R¹³)C(O)R¹³, -N(R¹³)N(R¹³)₂, -N(R¹³)C(O)OR¹³, -N(R¹³)C(O)N(R¹³)₂, -S(O)R¹³, -S(O)N(R¹³)₂ o -S(O)₂N(R¹³)₂, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; o R³ᵃ y R³ᵇ se toman juntos y son alquileno C₂₋₁₂, alquenileno C₂₋₁₂ o alquinileno C₂₋₁₂; donde cada uno del alquileno C₂₋₁₂, alquenileno C₂₋₁₂, alquinileno C₂₋₁₂ y carbociclilo de 3 - 6 miembros se sustituyen opcionalmente con uno o más R²¹; R⁴ es H, halo, -NO₂, -CN, -N₃, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, -C(O)R¹³, -C(S)R¹³, -C(O)OR¹³, -C(S)SR¹³, -C(O)SR¹³, -C(S)OR¹³, -SC(O)R¹³, -OC(S)R¹³, -SC(S)R¹³, -C(O)N(R¹³)₂, -OR¹¹, -SR¹⁴, -N(R¹²)₂, -N(R¹³)OR¹³, -N(R¹³)S(O)₂R¹³, -N(R¹³)C(O)R¹³, -N(R¹³)N(R¹³)₂, -N(R¹³)C(O)OR¹³, -N(R¹³)C(O)N(R¹³)₂, -S(O)₂R¹³, -S(O)R¹³, -S(O)N(R¹³)₂, -S(O)₂N(R¹³)₂, -N⁺(R¹³)₃, -S⁺(R¹³)₂ o -Si(R¹³)₃, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; «⁻ ⁻ ⁻ ⁻ ⁻ ⁻» es un enlace simple o un enlace doble, donde cuando «⁻ ⁻ ⁻ ⁻ ⁻ ⁻» es un enlace doble, entonces R⁵ se encuentra ausente; y cuando «⁻ ⁻ ⁻ ⁻ ⁻ ⁻» es un enlace simple, entonces R⁵ es H, halo, -NO₂, -CN, -N₃, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, -C(O)R¹³, -C(S)R¹³, -C(O)OR¹³, -C(S)SR¹³, -C(O)SR¹³, -C(S)OR¹³, -SC(O)R¹³, -OC(S)R¹³, -SC(S)R¹³, -C(O)N(R¹³)₂, -OR¹¹, -SR¹⁴, -N(R¹²)₂, -N(R¹³)OR¹³, -N(R¹³)S(O)₂R¹³, -N(R¹³)C(O)R¹³, -N(R¹³)N(R¹³)₂, -N(R¹³)C(O)OR¹³, -N(R¹³)C(O)N(R¹³)₂, -S(O)₂R¹³, -S(O)R¹³, -S(O)N(R¹³)₂, -S(O)₂N(R¹³)₂, -N⁺(R¹³)₃, -S⁺(R¹³)₂ o -Si(R¹³)₃, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; o R⁵ y R³ᵇ se toman junto con los carbonos con los que se acopla cada uno para formar un carbociclilo de 3 - 6 miembros, donde el carbociclilo de 3 - 6 miembros se sustituye opcionalmente con uno o más R²¹; R⁶, en cada aparición, es independientemente halo, -NO₂, -CN, -N₃, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, -C(O)R¹³, -C(S)R¹³, -C(O)OR¹¹, -C(S)SR¹³, -C(O)SR¹³, -C(S)OR¹³, -SC(O)R¹³, -OC(S)R¹³, -SC(S)R¹³, -C(O)N(R¹¹)₂, -OR¹¹, -SR¹⁴, -N(R¹²)₂, -N(R¹³)OR¹³, -N(R¹³)S(O)₂R¹³, -N(R¹³)C(O)R¹³, -N(R¹³)N(R¹³)₂, -N(R¹³)C(O)OR¹³, -N(R¹³)C(O)N(R¹³)₂, -S(O)₂R¹³, -S(O)R¹³, -S(O)N(R¹³)₂, -S(O)₂N(R¹³)₂, -N⁺(R¹³)₃, -S⁺(R¹³)₂ o -Si(R¹³)₃; o dos R⁶ unidos al mismo carbono del anillo para formar un oxo, =NR¹⁴ o alquilideno C₁₋₁₂, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros, heterociclilo de 3 a 12 miembros y alquilideno C₁₋₁₂ se sustituye opcionalmente con uno o más R²¹; X es NRᵇ u O; Rᵇ es H, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, -C(O)Rᶜ, -C(O)ORᶜ, -C(O)NRᶜRᶜ, -S(O)₂Rᶜ, -S(O)₂ORᶜ o -S(O)₂NRᶜRᶜ, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; Rᶜ, en cada aparición, se selecciona independientemente de H, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros y un heterociclilo de 3 a 12 miembros, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; R¹¹, en cada aparición, se selecciona independientemente de H, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros, acilo C₁₋₁₂ y -Si(R¹³)₃, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros, heterociclilo de 3 a 12 miembros y acilo C₁₋₁₂ se sustituye opcionalmente con uno o más R²¹; R¹², en cada aparición, se selecciona independientemente de H, alquilo C₁₋₁₂, alcoxi C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros y -Si(R¹³)₃, donde cada uno del alquilo C₁₋₁₂, alcoxi C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; R¹³, en cada aparición, se selecciona independientemente de H, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros y un heterociclilo de 3 a 12 miembros, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con uno o más R²¹; R¹⁴, en cada aparición, se selecciona independientemente de H, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, un carbociclilo de 3 a 12 miembros, un heterociclilo de 3 a 12 miembros y acilo C₁₋₁₂, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, carbociclilo de 3 a 12 miembros, heterociclilo de 3 a 12 miembros y acilo C₁₋₁₂ se sustituye opcionalmente con uno o más R²¹; R²¹, en cada aparición, se selecciona independientemente de halo, -OH, -S(O)₂R¹⁶, alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, alcoxi C₁₋₁₂, un carbociclilo de 3 a 12 miembros y un heterociclilo de 3 a 12 miembros, donde cada uno del alquilo C₁₋₁₂, alquenilo C₂₋₁₂, alquinilo C₂₋₁₂, alcoxi C₁₋₁₂, carbociclilo de 3 a 12 miembros y heterociclilo de 3 a 12 miembros se sustituye opcionalmente con 1 a 3 grupos que se seleccionan de halo, -OH, alquilo C₁₋₄ y alcoxi C₁₋₄; R¹⁶, en cada aparición, se selecciona independientemente de H o alquilo C₁₋₁₂; n es 0 o un entero de 1 a 8; p es 0, 1 ó 2; y q es 1, 2 ó 3, siempre que la suma de p y q no sea 4 ni 5.
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UY37551A (es) | 2018-07-31 |
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US20210340107A1 (en) | 2021-11-04 |
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