AR097571A1 - Compuestos espirocíclicos como inhibidores de la triptofano hidroxilasa - Google Patents
Compuestos espirocíclicos como inhibidores de la triptofano hidroxilasaInfo
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- AR097571A1 AR097571A1 ARP140103327A ARP140103327A AR097571A1 AR 097571 A1 AR097571 A1 AR 097571A1 AR P140103327 A ARP140103327 A AR P140103327A AR P140103327 A ARP140103327 A AR P140103327A AR 097571 A1 AR097571 A1 AR 097571A1
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- Prior art keywords
- alkyl
- nrc1rd1
- cycloalkyl
- aryl
- ora1
- Prior art date
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Abstract
Tratar aquellas enfermedades o aquellos trastornos que están asociados a la serotonina periférica, como es el caso de las enfermedades gastrointestinales, cardiovasculares, pulmonares, inflamatorias, metabólicas o asociadas a una masa ósea reducida, así como el síndrome de la serotonina y el cáncer. Reivindicación 1: Un compuesto caracterizado porque es de fórmula (1), o una sal farmacéuticamente aceptable del mismo, donde: el Anillo A es C₃₋₁₀ cicloalquilo, C₆₋₁₀ arilo, heterocicloalquilo de entre 4 y 10 miembros, o heteroarilo de entre 5 y 10 miembros; L es O ó NR⁴; W es N o CR⁵; X es N o CR⁶; Y es N o CR⁷; donde solo uno de X e Y es N; R¹ es H, C₁₋₁₀ alquilo, C₃₋₁₀ cicloalquilo, fenilo, -(CR⁸R⁹)ₚOC(O)R¹⁰, -(CR⁸R⁹)ₚNR¹¹R¹², o -(CR⁸R⁹)ₚC(O)NR¹¹R¹², donde dicho C₁₋₁₀ alquilo, C₃₋₁₀ cicloalquilo, y fenilo está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre F, Cl, Br, CN, C₁₋₄ alquilo, y C₁₋₄ haloalquilo; R² y R³ se seleccionan en forma independiente entre sí entre H, C₁₋₄ alquilo, y C₁₋₄ haloalquilo; R⁴ es H o C₁₋₄ alquilo; R⁵ y R⁶ se seleccionan en forma independiente entre sí entre H, halo, y C₁₋₄ alquilo; R⁷ es H, C₁₋₄ alquilo, C₂₋₆ alquenilo, C₆₋₁₀ cicloalquilo, C₆₋₁₀ cicloalquil-C₁₋₄ alquilo, C₆₋₁₀ arilo, C₆₋₁₀ aril-C₁₋₄ alquilo, heterocicloalquilo de entre 4 y 10 miembros, (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, heteroarilo de entre 5 y 10 miembros, (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, NR¹³R¹⁴, OR¹⁵, C(O)R¹⁶, S(O)qR¹⁷, donde dicho C₁₋₄ alquilo, C₂₋₆ alquenilo, C₆₋₁₀ cicloalquilo, C₆₋₁₀ cicloalquil-C₁₋₄ alquilo, C₆₋₁₀ arilo, C₆₋₁₀ aril-C₁₋₄ alquilo, heterocicloalquilo de entre 4 y 10 miembros, (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, heteroarilo de entre 5 y 10 miembros, y (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo está opcionalmente sustituido en cada caso con 1, 2, ó 3 sustituyentes seleccionados entre halo, C₁₋₄ alquilo, C₂₋₆ alquenilo, amino, C₁₋₄ alquilamino, C₂₋₆ dialquilamino, hidroxi, y C₁₋₄ alcoxi; R⁸ y R⁹ se seleccionan en forma independiente entre sí entre H y C₁₋₄ alquilo; R¹⁰ es C₁₋₆ alquilo opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre C₁₋₆ haloalquilo, C₆₋₁₀ cicloalquilo, ORᵃ, y NRᶜRᵈ; R¹¹ y R¹² se seleccionan en forma independiente entre sí entre H y C₁₋₆ alquilo; R¹³ es H o C₁₋₄ alquilo; R¹⁴ es H, C₁₋₄ alquilo, C₃₋₇ cicloalquilo, C₆₋₁₀ cicloalquil-C₁₋₄ alquilo, C₆₋₁₀ arilo, C₆₋₁₀ aril-C₁₋₄ alquilo, heterocicloalquilo de entre 4 y 10 miembros, (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, heteroarilo de entre 5 y 10 miembros, o (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, C(O)Rᵇ¹, C(O)ORᵃ¹, C(O)NRᶜ¹Rᵈ¹, S(O)Rᵇ¹, S(O)₂Rᵇ¹, o S(O)₂NRᶜ¹Rᵈ¹, donde dicho C₁₋₄ alquilo, C₃₋₇ cicloalquilo, C₃₋₇ cicloalquil-C₁₋₄ alquilo, C₆₋₁₀ arilo, C₆₋₁₀ aril-C₁₋₄ alquilo, heterocicloalquilo de entre 4 y 10 miembros, (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, heteroarilo de entre 5 y 10 miembros, y (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo está opcionalmente sustituido en cada caso con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre halo, C₁₋₄ alquilo, C₁₋₄ haloalquilo, CN, NO₂, 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, NRᶜ¹S(O)Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, y S(O)₂NRᶜ¹Rᵈ¹; o R¹³ y R¹⁴ junto con el átomo de N al cual están unidos forman un grupo heterocicloalquilo de 4, 5, 6 ó 7 miembros opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre C₁₋₆ alquilo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀ arilo, heteroarilo de 5 ó 6 miembros, halo, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ¹C(O)ORᵃ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, y S(O)₂NRᶜ¹Rᵈ¹, donde dicho C₁₋₆ alquilo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀ arilo, y heteroarilo de 5 ó 6 miembros está opcionalmente sustituido en cada caso con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre halo, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵃ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ¹C(O)ORᵃ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹,y S(O)₂NRᶜ¹Rᵈ¹; R¹⁵ es H, C₁₋₄ alquilo, C₃₋₇ cicloalquilo, C₃₋₇ cicloalquilo -C₁₋₄ alquilo, C₆₋₁₀ arilo, C₆₋₁₀ aril-C₁₋₄ alquilo, heterocicloalquilo de entre 4 y 10 miembros, (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, heteroarilo de entre 5 y 10 miembros, o (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, donde dicho C₁₋₄ alquilo, C₃₋₇ cicloalquilo, C₃₋₇ cicloalquil-C₁₋₄ alquilo, C₆₋₁₀ arilo, C₆₋₁₀ aril-C₁₋₄ alquilo, heterocicloalquilo de entre 4 y 10 miembros, (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, heteroarilo de entre 5 y 10 miembros, y (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo está opcionalmente sustituido en cada caso con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre halo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀ arilo, heteroarilo de 5 e 6 miembros, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ¹C(O)ORᵃ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, y S(O)₂NRᶜ¹Rᵈ¹; R¹⁶ es C₁₋₄ alquilo o NR¹⁸ᵃR¹⁸ᵇ donde dicho C₁₋₄ alquilo está opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre halo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀arilo, heteroarilo de 5 ó 6 miembros, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ¹C(O)ORᵃ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, y S(O)₂NRᶜ¹Rᵈ¹, R¹⁷ es C₁₋₄, alquilo, NR¹⁸ᵃR¹⁸ᵇ, o OR¹⁸ᶜ, donde dicho C₁₋₄ alquilo está opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre halo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀arilo, heteroarilo de 5 ó 6 miembros, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ¹C(O)ORᵃ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, y S(O)₂NRᶜ¹Rᵈ¹; R¹⁸ᵃ y R¹⁸ᵇ se seleccionan en forma independiente entre sí entre H y C₁₋₄ alquilo donde dicho C₁₋₄ alquilo está opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre halo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀ arilo, heteroarilo de 5 ó 6 miembros, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ⁴C(O)ORᵃ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, y S(O)₂NRᶜ¹Rᵈ¹; o R¹⁸ᵃ y R¹⁸ᵇ junto con el átomo de N al cual están unidos forman un grupo heterocicloalquilo de 4, 5, 6 ó 7 miembros opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre C₁₋₆ alquilo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀ arilo, heteroarilo de 5 ó 6 miembros halo, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ¹C(O)ORᵃ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, y S(O)₂NRᶜ¹Rᵈ¹ donde dicho C₁₋₆ alquilo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀ arilo, y heteroarilo de 5 ó 6 miembros está opcionalmente sustituido en cada caso con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre halo, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ¹C(O)ORᵃ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, y S(O)₂NRᶜ¹Rᵈ¹; R¹⁸ᶜ es H, C₁₋₆ alquilo, C₃₋₁₀ cicloalquilo, C₃₋₇ cicloalquil-C₁₋₄ alquilo, C₆₋₁₀ arilo, C₆₋₁₀ aril-C₁₋₄ alquilo, heterocicloalquilo de entre 4 y 10 miembros, (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, heteroarilo de entre 5 y 10 miembros, o (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, donde dicho C₁₋₄ alquilo, C₃₋₇ cicloalquilo, C₃₋₁₀ cicloalquil-C₁₋₄ alquilo, C₆₋₁₀ arilo, C₆₋₁₀ aril-C₁₋₄ alquilo, heterocicloalquilo de entre 4 y 10 miembros, (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, heteroarilo de entre 5 y 10 miembros, y (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo está opcionalmente sustituido en cada caso con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre halo, C₁₋₄ alquilo, C₁₋₄ haloalquilo, CN, ORᵃ¹, SRᵃ¹, C(O)Rᵇ¹, C(O)NRᶜ¹Rᵈ¹, C(O)ORᵃ¹, OC(O)Rᵇ¹, OC(O)NRᶜ¹Rᵈ¹, NRᶜ¹Rᵈ¹, NRᶜ¹C(O)Rᵇ¹, NRᶜ¹C(O)NRᶜ¹Rᵈ¹, NRᶜ¹C(O)ORᵃ¹, S(O)Rᵇ¹, S(O)NRᶜ¹Rᵈ¹, S(O)₂Rᵇ¹, NRᶜ¹S(O)₂Rᵇ¹, NRᶜ¹S(O)₂NRᶜ¹Rᵈ¹, y S(O)₂NRᶜ¹Rᵈ¹; RA es H, Cy¹, halo, C₁₋₆ alquilo, C₂₋₆ alquenilo, CN, NO₂, 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, NRᶜ²S(O)Rᵇ², NRᶜ²S(O)₂Rᵇ², NRᶜ²S(O)₂NRᶜ²Rᵈ², S(O)Rᵇ², S(O)NRᶜ²Rᵈ², S(O)₂Rᵇ², o S(O)₂NRᶜ²Rᵈ², donde dicho C₁₋₆ alquilo y C₂₋₆ alquenilo está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre Cy¹, halo, C₁₋₆ alquilo, C₂₋₆ alquenilo, C₁₋₆ haloalquilo, CN, NO₂, 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, NRᶜ²S(O)Rᵇ², NRᶜ²S(O)₂Rᵇ², NRᶜ²S(O)₂NRᶜ²Rᵈ², S(O)Rᵇ², S(O)NRᶜ²Rᵈ², S(O)₂Rᵇ², o S(O)₂NRᶜ²Rᵈ²; RB es H, Cy², halo, C₁₋₆ alquilo, C₂₋₆ alquenilo, C₁₋₆ haloalquilo, CN, NO₂, 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, NRᶜ³S(O)Rᵇ³, NRᶜ³S(O)₂Rᵇ³, NRᶜ³S(O)₂NRᶜ³Rᵈ³, S(O)Rᵇ³, S(O)NRᶜ³Rᵈ³, S(O)₂Rᶜ³, o S(O)₂NRᶜ³Rᵈ³, donde dicho C₁₋₆ alquilo y C₂₋₆ alquenilo está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre Cy², halo, C₁₋₆ alquilo, C₂₋₆ alquenilo, C₁₋₆ haloalquilo, CN, NO₂, 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, NRᶜ³S(O)Rᵇ³, NRᶜ³S(O)₂Rᵇ³, NRᶜ³S(O)₂NRᶜ³Rᵈ³, S(O)Rᵇ³, S(O)NRᶜ³Rᵈ³, S(O)₂Rᶜ³, o S(O)₂NRᶜ³Rᵈ³; RC y RD se seleccionan en forma independiente entre H, halo, C₁₋₆ alquilo, C₂₋₆ alquenilo, C₁₋₆ haloalquilo, CN, NO₂, ORᵃ⁴, SRᵃ⁴, C(O)Rᵇ⁴, C(O)NRᶜ⁴Rᵈ⁴, C(O)ORᵃ⁴, OC(O)Rᵃ⁴, OC(O)NRᶜ⁴Rᵈ⁴, NRᶜ⁴Rᵈ⁴, NRᶜ⁴C(O)Rᵇ⁴, NRᶜ⁴C(O)ORᵃ⁴, NRᶜ⁴C(O)NRᶜ⁴Rᵈ⁴, NRᶜ⁴S(O)Rᵇ⁴, NRᶜ⁴S(O)₂Rᵇ⁴, NRᶜ⁴S(O)₂NRᶜ⁴Rᵈ⁴, S(O)Rᵇ⁴, S(O)NRᶜ⁴Rᵈ⁴, S(O)₂Rᶜ⁴, y S(O)₂NRᶜ⁴Rᵈ⁴; donde dicho C₁₋₆ alquilo y C₂₋₆ alquenilo está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, heterocicloalquilo de entre 4 y 10 miembros, halo, C₁₋₆ alquilo, C₂₋₆ alquenilo, C₁₋₆ haloalquilo, CN, NO₂, ORᵃ⁴, SRᵃ⁴, C(O)Rᵇ⁴, C(O)NRᶜ⁴Rᵈ⁴, C(O)ORᵃ⁴, OC(O)Rᵃ⁴, OC(O)NRᶜ⁴Rᵈ⁴, NRᶜ⁴Rᵈ⁴, NRᶜ⁴C(O)Rᵇ⁴, NRᶜ⁴C(O)ORᵃ⁴, NRᶜ⁴C(O)NRᶜ⁴Rᵈ⁴, NRᶜ⁴S(O)Rᵇ⁴, NRᶜ⁴S(O)₂Rᵇ⁴, NRᶜ⁴S(O)₂NRᶜ⁴Rᵈ⁴, S(O)Rᵇ⁴, S(O)NRᶜ⁴Rᵈ⁴, S(O)₂Rᶜ⁴, y S(O)₂NRᶜ⁴Rᵈ⁴; Cy¹ y Cy² se seleccionan en forma independiente entre sí entre C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, y heterocicloalquilo de entre 4 y 10 miembros, cada uno de los cuales está opcionalmente sustituido con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre RCʸ; cada RCʸ se selecciona en forma independiente entre halo, C₁₋₆ alquilo, C₁₋₆ haloalquilo, C₂₋₆ alquenilo, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, heterocicloalquilo de entre 4 y 10 miembros, CN, NO₂, ORᵃ⁵, SRᵃ⁵, C(O)Rᶜ⁵, C(O)NRᶜ⁵Rᵈ⁵, C(O)ORᵃ⁵, OC(O)Rᵇ⁵, OC(O)NRᶜ⁵Rᵈ⁵, NRᶜ⁵Rᵈ⁵, NRᶜ⁵C(O)Rᵇ⁵, NRᶜ⁵C(O)ORᵃ⁵, NRᶜ⁵C(O)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 C₁₋₆ alquilo, C₂₋₆ alquenilo C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, y heterocicloalquilo de entre 4 y 10 miembros está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre halo, C₁₋₆ alquilo, CN, NO₂, ORᵃ⁵, SRᵃ⁵, C(O)Rᶜ⁵, C(O)NRᶜ⁵Rᵈ⁵, C(O)ORᵃ⁵, OC(O)Rᵇ⁵, OC(O)NRᶜ⁵Rᵈ⁵, NRᶜ⁵Rᵈ⁵, NRᶜ⁵C(O)Rᵇ⁵, NRᶜ⁵C(O)ORᵃ⁵, NRᶜ⁵C(O)NRᶜ⁵Rᵈ⁵, NRᶜ⁵S(O)Rᵇ⁵, NRᶜ⁵S(O)₂Rᵇ⁵, NRᶜ⁵S(O)₂NRᶜ⁵Rᵈ⁵, S(O)Rᵇ⁵, S(O)NRᶜ⁵Rᵈ⁵, S(O)₂Rᵇ⁵, y S(O)₂NRᶜ⁵Rᵈ⁵; cada Rᵃ, Rᵃ¹, Rᵃ², Rᵃ³, Rᵃ⁴, y Rᵃ⁵ se selecciona en forma independiente entre H, C₁₋₆ alquilo, C₁₋₄ haloalquilo, C₂₋₆ alquenilo, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, heterocicloalquilo de entre 4 y 10 miembros, C₆₋₁₀ aril-C₁₋₄ alquilo, C₃₋₁₀ cicloalquil-C₁₋₄ alquilo, (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, o (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, donde dicho C₁₋₆ alquilo, C₂₋₆ alquenilo, C₆₋₁₀ arilo, C₃₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, heterocicloalquilo de entre 4 y 10 miembros, C₆₋₁₀ aril-C₁₋₄ alquilo, C₃₋₁₀ cicloalquil-C₁₋₄ alquilo, (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, y (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre C₁₋₄ alquilo, halo, CN, ORᵃ⁶, C(O)Rᵇ⁶, C(O)NRᶜ⁶Rᵈ⁶, C(O)ORᵃ⁶, OC(O)Rᵇ⁶, OC(O)NRᶜ⁶Rᵈ⁶, NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(O)Rᵇ⁶, NRᶜ⁶C(O)NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(O)ORᵃ⁶, S(O)Rᵇ⁶, S(O)NRᶜ⁶Rᵈ⁶, S(O)₂Rᵇ⁶, NRᶜ⁶S(O)₂Rᵇ⁶, NRᶜ⁶S(O)₂NRᶜ⁶Rᵈ⁶, y S(O)₂NRᶜ⁶Rᵈ⁶; cada Rᵇ¹, Rᵇ², Rᵇ³, Rᵇ⁴ y Rᵇ⁵ se selecciona en forma independiente entre H, C₁₋₆ alquilo, C₁₋₄ haloalquilo, C₂₋₆ alquenilo, C₆₋₁₀ arilo, C₆₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, heterocicloalquilo de entre 4 y 10 miembros, C₆₋₁₀ aril-C₁₋₄ alquilo, C₆₋₁₀ cicloalquil-C₁₋₄ alquilo, (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, o (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, donde dicho C₁₋₆ alquilo, C₂₋₆ alquenilo, C₆₋₁₀ arilo, C₆₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, heterocicloalquilo de entre 4 y 10 miembros, C₆₋₁₀ aril-C₁₋₄ alquilo, C₆₋₁₀ cicloalquil-C₁₋₄ alquilo, (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, y (heterocicloalquilo de entre 4 y 10 miembros)- C₁₋₄ alquilo está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre C₁₋₄ alquilo, halo, CN, ORᵃ⁶, C(O)Rᵇ⁶, C(O)NRᶜ⁶Rᵈ⁶, C(O)ORᵃ⁶, OC(O)Rᵇ⁶, OC(O)NRᶜ⁶Rᵈ⁶, NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(O)Rᵇ⁶, NRᶜ⁶C(O)NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(O)ORᵃ⁶, S(O)Rᵇ⁶, S(O)NRᶜ⁶Rᵈ⁶, S(O)₂Rᵇ⁶, NRᶜ⁶S(O)₂Rᵇ⁶, NRᶜ⁶S(O)₂NRᶜ⁶Rᵈ⁶, y S(O)₂NRᶜ⁶Rᵈ⁶; cada Rᶜ, Rᵈ, Rᶜ¹, Rᵈ¹, Rᶜ² Rᵈ², Rᶜ³, Rᵈ³, Rᶜ⁴, Rᵈ⁴, Rᶜ⁵, y Rᵈ⁵ Se selecciona en forma independiente entre H, C₁₋₆ alquilo, C₁₋₄ haloalquilo, C₂₋₆ alquenilo, C₆₋₁₀ arilo, C₆₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, heterocicloalquilo de entre 4 y 10 miembros, C₆₋₁₀ aril-C₁₋₄ alquilo, C₆₋₁₀ cicloalquil-C₁₋₄ alquilo, (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, o (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo, donde dicho C₁₋₆ alquilo, C₂₋₆ alquenilo, C₆₋₁₀ arilo, C₆₋₁₀ cicloalquilo, heteroarilo de entre 5 y 10 miembros, heterocicloalquilo de entre 4 y 10 miembros, C₆₋₁₀ aril-C₁₋₄ alquilo, C₆₋₁₀ cicloalquil-C₁₋₄ alquilo, (heteroarilo de entre 5 y 10 miembros)-C₁₋₄ alquilo, y (heterocicloalquilo de entre 4 y 10 miembros)-C₁₋₄ alquilo está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre C₁₋₄, alquilo, halo, CN, ORᵃ⁶, C(O)Rᵇ⁶, C(O)NRᶜ⁶Rᵈ⁶, C(O)ORᵃ⁶, OC(O)Rᵇ⁶, OC(O)NRᶜ⁶Rᵈ⁶, NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(O)Rᵇ⁶, NRᶜ⁶C(O)NRᶜ⁶Rᵈ⁶, NRᶜ⁶C(O)ORᵃ⁶, S(O)Rᵇ⁶, S(O)NRᶜ⁶Rᵈ⁶, S(O)₂Rᵇ⁶, NRᶜ⁶S(O)₂Rᵇ⁶, NRᶜ⁶S(O)₂NRᶜ⁶Rᵈ⁶, y S(O)₂NRᶜ⁶Rᵈ⁶ o cualquier Rc y Rd junto con el átomo de N al cual están unidos forman un grupo heterocicloalquilo de 4, 5, 6 ó 7 miembros opcionalmente sustituido con 1, 2, ó 3 sustituyentes seleccionados en forma independiente entre C₁₋₆ alquilo, C₃₋₇ cicloalquilo, heterocicloalquilo de entre 4 y 7 miembros, C₆₋₁₀ arilo, heteroarilo de 5 ó 6 miembros, halo CN, ORᵃ⁶, C(O)Rᵇ⁶, C(O)NRᶜ⁶Rᵈ⁶, C(O)ORᵃ⁶, OC(O)Rᵇ⁶, OC(O)NRᶜ⁶Rᵈ⁶,
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