AR101174A1 - Imidazopirazinas como inhibidores de lsd1 - Google Patents
Imidazopirazinas como inhibidores de lsd1Info
- Publication number
- AR101174A1 AR101174A1 ARP150102197A ARP150102197A AR101174A1 AR 101174 A1 AR101174 A1 AR 101174A1 AR P150102197 A ARP150102197 A AR P150102197A AR P150102197 A ARP150102197 A AR P150102197A AR 101174 A1 AR101174 A1 AR 101174A1
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- nrc7rd7
- alkyl
- nrc7c
- ora7
- independently selected
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Abstract
La presente se dirige a derivados de imidazo[1,2-a]pirazina que son inhibidores de LSD1 útiles en el tratamiento de enfermedades tales como cáncer. Reivindicación 1: Un compuesto de fórmula (1), o una de sus sales farmacéuticamente aceptables, caracterizado porque: el anillo A es arilo C₆₋₁₀ o heteroarilo de 5 - 10 miembros que comprende carbono y 1, 2, 3, ó 4 heteroátomos seleccionados de N, O, y S, donde dicho arilo C₆₋₁₀ y heteroarilo de 5 - 10 miembros están opcionalmente sustituidos con 1, 2, 3, ó 4 sustituyentes seleccionados de modo independiente de RA; el anillo B es arilo C₆₋₁₀; heteroarilo de 5 - 10 miembros que comprende carbono y 1, 2, 3 ó 4 heteroátomos seleccionados de N, O, y S; cicloalquilo C₃₋₁₀; o heterocicloalquilo de 4 - 10 miembros que comprende carbono y 1, 2, 3 ó 4 heteroátomos seleccionados de N, O, y S; donde dicho arilo C₆₋₁₀, heteroarilo de 5 - 10 miembros, cicloalquilo C₃₋₁₀, y heterocicloalquilo de 4 - 10 miembros están opcionalmente sustituidos con 1, 2, 3, ó 4 sustituyentes seleccionados de modo independiente de RB; R¹ es halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, Cy¹, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)ORᵃ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, C(=NRᵉ¹)Rᵇ¹, C(=NRᵉ¹)NRᶜ¹Rᵈ¹, NRᶜ¹C(=NRᵉ¹)NRᶜ¹Rᵈ¹, NRᶜ¹S(O)Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, o S(O)₂NRᶜ¹Rᵈ¹; donde dicho alquilo C₁₋₆, alquenilo C₂₋₆, y alquinilo C₂₋₆ están opcionalmente sustituidos con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de Cy¹, halo, CN, OH, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)ORᵃ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, C(=NRᵉ¹)Rᵇ¹, C(=NRᵉ¹)NRᶜ¹Rᵈ¹, NRᶜ¹C(=NRᵉ¹)NRᶜ¹Rᵈ¹, NRᶜ¹S(O)Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, y S(O)₂NRᶜ¹Rᵈ¹; R² y R³ se seleccionan de modo independiente de H, halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, Cy², CN, ORᵃ², SRᵃ², C(O)Rᵇ², C(O)NRᶜ²Rᵈ², C(O)ORᵃ², OC(O)Rᵇ², OC(O)NRᶜ²Rᵈ², NRᶜ²Rᵈ², NRᶜ²C(O)Rᵇ², NRᶜ²C(O)ORᵃ², NRᶜ²C(O)NRᶜ²Rᵈ², C(=NRᵉ²)Rᵇ², C(=NRᵉ²)NRᶜ²Rᵈ², NRᶜ²C(=NRᵉ²)NRᶜ²Rᵈ², NRᶜ²S(O)Rᵇ², NRᶜ²S(O)₂Rᵇ², NRᶜ²S(O)₂NRᶜ²Rᵈ², S(O)Rᵇ², S(O)NRᶜ²Rᵈ², S(O)₂Rᵇ², y S(O)₂NRᶜ²Rᵈ²; donde dicho alquilo C₁₋₆, alquenilo C₂₋₆, y alquinilo C₂₋₆ están opcionalmente sustituidos con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de Cy², halo, CN, ORᵃ², SRᵃ², C(O)Rᵇ², C(O)NRᶜ²Rᵈ², C(O)ORᵃ², OC(O)Rᵇ², OC(O)NRᶜ²Rᵈ², NRᶜ²Rᵈ², NRᶜ²C(O)Rᵇ², NRᶜ²C(O)ORᵃ², NRᶜ²C(O)NRᶜ²Rᵈ², C(=NRᵉ²)Rᵇ², C(=NRᵉ²)NRᶜ²Rᵈ², NRᶜ²C(=NRᵉ²)NRᶜ²Rᵈ², NRᶜ²S(O)Rᵇ², NRᶜ²S(O)₂Rᵇ², NRᶜ²S(O)₂NRᶜ²Rᵈ², S(O)Rᵇ², S(O)NRᶜ²Rᵈ², S(O)₂Rᵇ², y S(O)₂NRᶜ²Rᵈ²; cada RA se selecciona de modo independiente de halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, CN, NO₂, ORᵃ⁴, SRᵃ⁴, C(O)Rᵇ⁴, C(O)NRᶜ⁴Rᵈ⁴, C(O)ORᵃ⁴, OC(O)Rᵇ⁴, OC(O)NRᶜ⁴Rᵈ⁴, NRᶜ⁴Rᵈ⁴, NRᶜ⁴C(O)Rᵇ⁴, NRᶜ⁴C(O)ORᵃ⁴, NRᶜ⁴C(O)NRᶜ⁴Rᵈ⁴, C(=NRᵉ⁴)Rᵇ⁴, C(=NRᵉ⁴)NRᶜ⁴Rᵈ⁴, NRᶜ⁴C(=NRᵉ⁴)NRᶜ⁴Rᵈ⁴, NRᶜ⁴S(O)Rᵇ⁴, NRᶜ⁴S(O)₂Rᵇ⁴, NRᶜ⁴S(O)₂NRᶜ⁴Rᵈ⁴, S(O)Rᵇ⁴, S(O)NRᶜ⁴Rᵈ⁴, S(O)₂Rᵇ⁴, y S(O)₂NRᶜ⁴Rᵈ⁴, donde dicho alquilo C₁₋₆, alquenilo C₂₋₆, y alquinilo C₂₋₆ están opcionalmente sustituidos con 1, 2, ó 3, sustituyentes seleccionados de modo independiente de halo, haloalquilo C₁₋₆, CN, NO₂, ORᵃ⁴, SRᵃ⁴, C(O)Rᵇ⁴, C(O)NRᶜ⁴Rᵈ⁴, C(O)ORᵃ⁴, OC(O)Rᵇ⁴, OC(O)NRᶜ⁴Rᵈ⁴, NRᶜ⁴Rᵈ⁴, NRᶜ⁴C(O)Rᵇ⁴, NRᶜ⁴C(O)ORᵃ⁴, NRᶜ⁴C(O)NRᶜ⁴Rᵈ⁴, C(=NRᵉ⁴)Rᵇ⁴, C(=NRᵉ⁴)NRᶜ⁴Rᵈ⁴, NRᶜ⁴C(=NRᵉ⁴)NRᶜ⁴Rᵈ⁴, NRᶜ⁴S(O)Rᵇ⁴, NRᶜ⁴S(O)₂Rᵇ⁴, NRᶜ⁴S(O)₂NRᶜ⁴Rᵈ⁴, S(O)Rᵇ⁴, S(O)NRᶜ⁴Rᵈ⁴, S(O)₂Rᵇ⁴, y S(O)₂NRᶜ⁴Rᵈ⁴; cada RB se selecciona de modo independiente de Cy³, halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, CN, NO₂, ORᵃ⁵, SRᵃ⁵, C(O)Rᵇ⁵, C(O)NRᶜ⁵Rᵈ⁵, C(O)ORᵃ⁵, OC(O)Rᵇ⁵, OC(O)NRᶜ⁵Rᵈ⁵, NRᶜ⁵Rᵈ⁵, NRᶜ⁵C(O)Rᵇ⁵, NRᶜ⁵C(O)ORᵃ⁵, NRᶜ⁵C(O)NRᶜ⁵Rᵈ⁵, C(=NRᵉ⁵)Rᵇ⁵, C(=NRᵉ⁵)NRᶜ⁵Rᵈ⁵, NRᶜ⁵C(=NRᵉ⁵)NRᶜ⁵Rᵈ⁵, NRᶜ⁵S(O)Rᵇ⁵, NRᶜ⁵S(O)₂Rᵇ⁵, NRᶜ⁵S(O)₂NRᶜ⁵Rᵈ⁵, S(O)Rᵇ⁵, S(O)NRᶜ⁵Rᵈ⁵, S(O)₂Rᵇ⁵, y S(O)₂NRᶜ⁵Rᵈ⁵, donde dicho alquilo C₁₋₆, alquenilo C₂₋₆, y alquinilo C₂₋₆ están opcionalmente sustituidos con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de Cy³, halo, haloalquilo C₁₋₆, CN, NO₂, ORᵃ⁵, SRᵃ⁵, C(O)Rᵇ⁵, C(O)NRᶜ⁵Rᵈ⁵, C(O)ORᵃ⁵, OC(O)Rᵇ⁵, OC(O)NRᶜ⁵Rᵈ⁵, NRᶜ⁵Rᵈ⁵, NRᶜ⁵C(O)Rᵇ⁵, NRᶜ⁵C(O)ORᵃ⁵, NRᶜ⁵C(O)NRᶜ⁵Rᵈ⁵, C(=NRᵉ⁵)Rᵇ⁵, C(=NRᵉ⁵)NRᶜ⁵Rᵈ⁵, NRᶜ⁵C(=NRᵉ⁵)NRᶜ⁵Rᵈ⁵, NRᶜ⁵S(O)Rᵇ⁵, NRᶜ⁵S(O)₂Rᵇ⁵, NRᶜ⁵S(O)₂NRᶜ⁵Rᵈ⁵, S(O)Rᵇ⁵, S(O)NRᶜ⁵Rᵈ⁵, S(O)₂Rᵇ⁵, y S(O)₂NRᶜ⁵Rᵈ⁵; cada Cy¹, Cy², Cy³, y Cy⁴ se selecciona de modo independiente de arilo C₆₋₁₀, cicloalquilo C₃₋₁₀, heteroarilo de 5 - 10 miembros, y heterocicloalquilo de 4 - 10 miembros, cada uno de los cuales está opcionalmente sustituido con 1, 2, 3, ó 4 sustituyentes seleccionados de modo independiente de RCʸ; cada RCʸ se selecciona de modo independiente de halo, alquilo C₁₋₄, haloalquilo C₁₋₄, cianoalquilo C₁₋₄, alquenilo C₂₋₆, alquinilo C₂₋₆, fenilo, cicloalquilo C₃₋₇, heteroarilo de 5 - 6 miembros, heterocicloalquilo de 4 - 7 miembros, fenil-alquil C₁₋₄-, cicloalquil C₃₋₇-alquil C₁₋₄-, (heteroarilo de 5 - 6 miembros)-alquil C₁₋₄-, y (heterocicloalquilo de 4 - 7 miembros)-alquil C₁₋₄-, CN, NO₂, ORᵃ⁶, SRᵃ⁶, C(O)Rᵇ⁶, C(O)NRᶜ⁶Rᵈ⁶, C(O)ORᵃ⁶, OC(O)Rᵇ⁶, OC(O)NRᶜ⁶Rᵈ⁶, C(=NRᵉ⁶)NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(=NRᵉ⁶)NRᶜ⁶Rᵈ⁶, NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(O)Rᵇ⁶, NRᶜ⁶C(O)ORᵃ⁶, NRᶜ⁶C(O)NRᶜ⁶Rᵈ⁶, NRᶜ⁶S(O)Rᵇ⁶, NRᶜ⁶S(O)₂Rᵇ⁶, NRᶜ⁶S(O)₂NRᶜ⁶Rᵈ⁶, S(O)Rᵇ⁶, S(O)NRᶜ⁶Rᵈ⁶, S(O)₂Rᵇ⁶, y S(O)₂NRᶜ⁶Rᵈ⁶, donde dicho alquilo C₁₋₄, alquenilo C₂₋₆, alquinilo C₂₋₆, fenilo, cicloalquilo C₃₋₇, heteroarilo de 5 - 6 miembros, heterocicloalquilo de 4 - 7 miembros, fenil-alquil C₁₋₄-, cicloalquil C₃₋₇-alquil C₁₋₄-, (heteroarilo de 5 - 6 miembros)-alquil C₁₋₄-, y (heterocicloalquilo de 4 - 7 miembros)-alquil C₁₋₄- están opcionalmente sustituidos con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de alquilo C₁₋₆, haloalquilo C₁₋₄, cianoalquilo C₁₋₆, halo, CN, NO₂, ORᵃ⁶, SRᵃ⁶, C(O)Rᵇ⁶, C(O)NRᶜ⁶Rᵈ⁶, C(O)ORᵃ⁶, OC(O)Rᵇ⁶, OC(O)NRᶜ⁶Rᵈ⁶, C(=NRᵉ⁶)NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(=NRᵉ⁶)NRᶜ⁶Rᵈ⁶, NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(O)Rᵇ⁶, NRᶜ⁶C(O)ORᵃ⁶, NRᶜ⁶C(O)NRᶜ⁶Rᵈ⁶, NRᶜ⁶S(O)Rᵇ⁶, NRᶜ⁶S(O)₂Rᵇ⁶, NRᶜ⁶S(O)₂NRᶜ⁶Rᵈ⁶, S(O)Rᵇ⁶, S(O)NRᶜ⁶Rᵈ⁶, S(O)₂Rᵇ⁶, y S(O)₂NRᶜ⁶Rᵈ⁶; cada Rᵃ¹ se selecciona de modo independiente de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y Cy⁴; donde dicho alquilo C₁₋₆, alquenilo C₂₋₆, y alquinilo C₂₋₆ están opcionalmente sustituidos con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de Cy⁴, halo, CN, ORᵃ³, SRᵃ³, C(O)Rᵇ³, C(O)NRᶜ³Rᵈ³, C(O)ORᵃ³, OC(O)Rᵇ³, OC(O)NRᶜ³Rᵈ³, NRᶜ³Rᵈ³, NRᶜ³C(O)Rᵇ³, NRᶜ³C(O)ORᵃ³, NRᶜ³C(O)NRᶜ³Rᵈ³, C(=NRᵉ³)Rᵇ³, C(=NRᵉ³)NRᶜ³Rᵈ³, NRᶜ³C(=NRᵉ³)NRᶜ³Rᵈ³, NRᶜ³S(O)Rᵇ³, NRᶜ³S(O)₂Rᵇ³, NRᶜ³S(O)₂NRᶜ³Rᵈ³, S(O)Rᵇ³, S(O)NRᶜ³Rᵈ³, S(O)₂Rᵇ³, y S(O)₂NRᶜ³Rᵈ³; cada Rᵇ¹, Rᶜ¹, y Rᵈ¹ se selecciona de modo independiente de H, alquilo C₁₋₆, haloalquilo C₁₋₄, alquenilo C₂₋₆, alquinilo C₂₋₆, arilo C₆₋₁₀, cicloalquilo C₃₋₁₀, heteroarilo de 5 - 10 miembros, heterocicloalquilo de 4 - 10 miembros, aril C₆₋₁₀-alquil C₁₋₄-, cicloalquil C₃₋₁₀-alquil C₁₋₄-, (heteroarilo de 5 - 10 miembros)-alquil C₁₋₄-, y (heterocicloalquilo de 4 - 10 miembros)-alquil C₁₋₄, donde dicho alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, arilo C₆₋₁₀, cicloalquilo C₃₋₁₀, heteroarilo de 5 - 10 miembros, heterocicloalquilo de 4 - 10 miembros, aril C₆₋₁₀-alquil C₁₋₄, cicloalquil C₃₋₁₀-alquil C₁₋₄-, (heteroarilo de 5 - 10 miembros)-alquil C₁₋₄-, y (heterocicloalquilo de 4 - 10 miembros)-alquil C₁₋₄- están opcionalmente sustituidos con 1, 2, 3, 4, ó 5 sustituyentes seleccionados de modo independiente de alquilo C₁₋₄, haloalquilo C₁₋₄, cianoalquilo C₁₋₄, halo, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷; o Rᶜ¹ y Rᵈ¹ juntos con un átomo de N al que están unidos forman un grupo heterocicloalquilo de a 4, 5, 6, ó 7 miembros opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de alquilo C₁₋₆, cicloalquilo C₃₋₇, heterocicloalquilo de 4 - 7 miembros, arilo C₆₋₁₀, heteroarilo de 5 - 6 miembros, haloalquilo CN, halo, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷, donde dicho alquilo C₁₋₆, cicloalquilo C₃₋₇, heterocicloalquilo de 4 - 7 miembros, arilo C₆₋₁₀, y heteroarilo de 5 - 6 miembros están opcionalmente sustituidos con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de halo, alquilo C₁₋₄, haloalquilo C₁₋₄, cianoalquilo C₁₋₄, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷ y S(O)₂NRᶜ⁷Rᵈ⁷; cada Rᵃ², Rᵇ², Rᶜ², y Rᵈ² se selecciona de modo independiente de H, alquilo C₁₋₆, haloalquilo C₁₋₄, alquenilo C₂₋₆, alquinilo C₂₋₆, arilo C₆₋₁₀, cicloalquilo C₃₋₁₀, heteroarilo de 5 - 10 miembros, heterocicloalquilo de 4 - 10 miembros, aril C₆₋₁₀-alquil C₁₋₄, cicloalquil C₃₋₁₀-alquil C₁₋₄-, (heteroarilo de 5 - 10 miembros)-alquil C₁₋₄-, y (heterocicloalquilo de 4 - 10 miembros)-alquil C₁₋₄, donde dicho alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, arilo C₆₋₁₀, cicloalquilo C₃₋₁₀, heteroarilo de 5 - 10 miembros, heterocicloalquilo de 4 - 10 miembros, aril C₆₋₁₀-alquil C₁₋₄-, cicloalquil C₃₋₁₀-alquil C₁₋₄, (heteroarilo de 5 - 10 miembros)-alquil C₁₋₄-, y (heterocicloalquilo de 4 - 10 miembros)-alquil C₁₋₄- están opcionalmente sustituidos con 1, 2, 3, 4, ó 5 sustituyentes seleccionados de modo independiente de alquilo C₁₋₄, haloalquilo C₁₋₄, cianoalquilo C₁₋₄, halo, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵇ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷; o Rᶜ² y Rᵈ² juntos con un átomo de N al que están unidos forman un grupo heterocicloalquilo de a 4, 5, 6, ó 7 miembros opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de alquilo C₁₋₆, cicloalquilo C₃₋₇, heterocicloalquilo de 4 - 7 miembros, fenilo, heteroarilo de 5 - 6 miembros, haloalquilo C₁₋₆, halo, CN, ORᵃ⁷, sRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷, donde dicho alquilo C₁₋₆, cicloalquilo C₃₋₇, heterocicloalquilo de 4 - 7 miembros, fenilo, y heteroarilo de 5 - 6 miembros están opcionalmente sustituidos con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de halo, alquilo C₁₋₄, haloalquilo C₁₋₄, cianoalquilo C₁₋₄, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, -S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷; cada Rᵃ³, Rᵇ³, Rᶜ³, y Rᵈ³ se selecciona de modo independiente de H, alquilo C₁₋₆, haloalquilo C₁₋₄, alquenilo C₂₋₆, alquinilo C₂₋₆, arilo C₆₋₁₀, cicloalquilo C₃₋₁₀, heteroarilo de 5 - 10 miembros, heterocicloalquilo de 4 - 10 miembros, aril C₆₋₁₀-alquil C₁₋₄-, cicloalquil C₃₋₁₀-alquil C₁₋₄-, (heteroarilo de 5 - 10 miembros)-alquil C₁₋₄-, y (heterocicloalquilo de 4 - 10 miembros)-alquil C₁₋₄-, donde dicho alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, arilo C₆₋₁₀, cicloalquilo C₃₋₁₀, heteroarilo de 5 - 10 miembros, heterocicloalquilo de 4 - 10 miembros, aril C₆₋₁₀-alquil C₁₋₄-, cicloalquil C₃₋₁₀-alquil C₁₋₄-, (heteroarilo de 5 - 10 miembros)-alquil C₁₋₄-, y (heterocicloalquilo de 4 - 10 miembros)-alquil C₁₋₄- están opcionalmente sustituidos con 1, 2, 3, 4, ó 5 sustituyentes seleccionados de modo independiente de alquilo C₁₋₄, haloalquilo C₁₋₄, cianoalquilo CH, halo, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵃ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷; o Rᶜ³ y Rᵈ³ juntos con un átomo de N al que están unidos forman un grupo heterocicloalquilo de a 4, 5, 6, ó 7 miembros opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de alquilo C₁₋₆, cicloalquilo C₃₋₇, heterocicloalquilo de 4 - 7 miembros, fenilo, heteroarilo de 5 - 6 miembros, haloalquilo C₁₋₆, halo, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵃ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷, donde dicho alquilo C₁₋₆, cicloalquilo C₃₋₇, heterocicloalquilo de 4 - 7 miembros, fenilo, y heteroarilo de 5 - 6 miembros están opcionalmente sustituidos con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de halo, alquilo C₁₋₄, haloalquilo C₁₋₄, cianoalquilo C₁₋₄, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷; cada Rᵃ⁴, Rᵇ⁴, Rᶜ⁴, y Rᵈ⁴ se selecciona de modo independiente de H, alquilo C₁₋₆, haloalquilo C₁₋₄, alquenilo C₂₋₆, y alquinilo C₂₋₆, donde dicho alquilo C₁₋₄, alquenilo C₂₋₆, y alquinilo C₂₋₆ están opcionalmente sustituidos con 1, 2, 3, 4, ó 5 sustituyentes seleccionados de modo independiente de alquilo C₁₋₄, haloalquilo C₁₋₄, cianoalquilo C₁₋₄, halo, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)Rᵇ⁷, NRᶜ⁷C(O)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(O)ORᵃ⁷, C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, NRᶜ⁷C(=NRᵉ⁷)NRᶜ⁷Rᵈ⁷, S(O)Rᵇ⁷, S(O)NRᶜ⁷Rᵈ⁷, S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂Rᵇ⁷, NRᶜ⁷S(O)₂NRᶜ⁷Rᵈ⁷, y S(O)₂NRᶜ⁷Rᵈ⁷; o Rᶜ⁴ y Rᵈ⁴ juntos con un átomo de N al que están unidos forman un grupo heterocicloalquilo de a 4, 5, 6, ó 7 miembros opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados de modo independiente de alquilo C₁₋₆, haloalquilo C₁₋₆, halo, CN, ORᵃ⁷, SRᵃ⁷, C(O)Rᵇ⁷, C(O)NRᶜ⁷Rᵈ⁷, C(O)ORᵃ⁷, OC(O)Rᵇ⁷, OC(O)NRᶜ⁷Rᵈ⁷,
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US10556908B2 (en) | 2020-02-11 |
TW201613925A (en) | 2016-04-16 |
US20170369497A1 (en) | 2017-12-28 |
US20190106426A1 (en) | 2019-04-11 |
US20160009720A1 (en) | 2016-01-14 |
US10112950B2 (en) | 2018-10-30 |
WO2016007736A1 (en) | 2016-01-14 |
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