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AR096788A1 - Compuestos tricíclicos de carboxamida como inhibidores potentes de rock - Google Patents

Compuestos tricíclicos de carboxamida como inhibidores potentes de rock

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Publication number
AR096788A1
AR096788A1 ARP140102466A ARP140102466A AR096788A1 AR 096788 A1 AR096788 A1 AR 096788A1 AR P140102466 A ARP140102466 A AR P140102466A AR P140102466 A ARP140102466 A AR P140102466A AR 096788 A1 AR096788 A1 AR 096788A1
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Patil Sharanabasappa
Wang Cailan
L Quan Mimi
Hu Zilun
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Bristol Myers Squibb Co
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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Abstract

Reivindicación 1: Un compuesto caracterizado por la fórmula (1), o un estereoisómero, un tautómero o una sal de aquel aceptable desde el punto de vista farmacéutico, en donde: A¹, A² son CR¹; A³ se selecciona independientemente de N y CR¹; B se selecciona independientemente de -O-, -CR³R⁴O-, -OCR³R⁴-, -NRᵃ-, -C(O)O-, -OC(O)-, -C(O)NRᵃ-, -NRᵃC(O)- y -S-; L se selecciona independientemente de -(CR⁶R⁷)q, -(CR⁶R⁷)ₛNR⁵(CR⁶R⁷)q-, -(CR⁶R⁷)ₛO(CR⁶R⁷)q- y -(CR⁶R⁷)ₛC(O)(CR⁶R⁷)q-; R¹ se selecciona independientemente de H, F, Cl, Br, CN, NRᵃRᵃ, -OC₁₋₄ alquilo sustituido con 0 - 3 Rᵉ, C₁₋₄ alquilo sustituido con 0 - 3 Rᵉ, -(CH₂)ʳORᵇ, (CH₂)ʳS(O)ₚRᶜ, -(CH₂)ʳC(=O)Rᵇ, -(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)(CH₂)ʳNRᵃRᵃ, (CH₂)ʳCN, -(CH₂)ʳNRᵃC(=O)Rᵇ, -(CH₂)ʳNRᵃC(=O)ORᵇ, -(CH₂)ʳOC(=O)NRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)ORᵇ, -(CH₂)ʳS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚRᶜ, (CH₂)ʳ-C₃₋₆ carbociclilo sustituido con 0 - 3 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 3 Rᵉ; R²,se selecciona independientemente de H, F, Cl, Br, CN, NRᵃRᵃ, -OC₁₋₄ alquilo sustituido con 0 - 3 Rᵉ, C₁₋₄ alquilo sustituido con 0 - 3 Rᵉ, -(CH₂)ʳORᵇ; R³ y R⁴ se seleccionan independientemente de H, F, OH, CN, NRᵃRᵃ, C₁₋₄ alquilo sustituido con 0 - 3 Rᵉ, C₁₋₄ alquenilo sustituido con 0 - 3 Rᵉ, y C₁₋₄ alquinilo sustituido con 0 - 3 Rᵉ, -(CH₂)ʳORᵇ, (CH₂)ʳS(O)ₚRᶜ, -(CH₂)ʳC(=O)Rᵇ, -(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)(CH₂)ʳNRᵃRᵃ, (CH₂)ʳCN, -(CH₂)ʳNRᵃC(=O)Rᵇ, -(CH₂)ʳNRᵃC(=O)ORᵇ, -(CH₂)ʳOC(=O)NRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)ORᵇ, -(CH₂)ʳS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚRᶜ, (CH₂)ʳ-C₃₋₆ carbociclilo sustituido con 0 - 3 Rᵉ, y -(CH₂)ʳ-heterociclilo sustituido con 0 - 3 Rᵉ; y -(CH₂)ʳ-heterociclilo sustituido con 0 - 3 Rᵉ; R⁵ se selecciona independientemente de H y C₁₋₄ alquilo opcionalmente sustituido con F, Cl, Br, CN, -ORᵇ, -S(O)ₚRᶜ, -C(=O)Rᵇ, -NRᵃRᵃ, -C(=O)NRᵃRᵃ, -C(=O)(CH₂)ʳNRᵃRᵃ, CN, -NRᵃC(=O)Rᵇ, -NRᵃC(=O)ORᵇ, -OC(=O)NRᵃRᵃ, -NRᵃC(=O)NRᵃRᵃ, -C(=O)ORᵇ, -S(O)ₚNRᵃRᵃ, -NRᵃS(O)ₚNRᵃRᵃ, y -NRᵃS(O)ₚRᶜ, -(CH₂)ʳ-C₃₋₁₀carbociclilo sustituido con 0 - 5 Rᵉ, y -(CH₂)ʳ-heterociclilo sustituido con 0 - 5 Rᵉ; R⁶ y R⁷ se seleccionan independientemente de H, C₁₋₄ alquilo sustituido con 0 - 4 Rᵉ, -(CH₂)ʳORᵇ, -(CH₂)ʳS(O)ₚRᶜ, -(CH₂)ʳC(=O)Rᵇ, -(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳC(=O)(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)Rᵇ, -(CH₂)ʳNRᵃC(=O)ORᵇ, -(CH₂)ʳOC(=O)NRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)ORᵇ, -(CH₂)ʳS(O)ₚNRᵃRᵃ -(CH₂)ʳNRᵃS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚRᶜ, (CH₂)ʳ-C₃₋₆ carbociclilo sustituido con 0 - 3 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 3 Rᵉ; alternativamente, R⁶ y R⁷, junto con el átomo de carbono al que están unidos, forman un cicloalquilo o heterociclilo, cada uno sustituido con 0 - 5 Rᵉ; alternativamente, cuando q es 2 ó 3, dos grupos adyacentes R⁶ forman un cicloalquilo o heterociclilo, cada uno sustituido con 0 - 5 Rᵉ; R⁸ se selecciona de C₃₋₁₀ carbociclilo y heterociclilo, cada uno sustituido con 0 - 5 Rᵉ; R⁹ se selecciona independientemente de F, Cl, Br, C₁₋₄ alquilo sustituido con 0 - 5 Rᵉ, C₂₋₄ alquenilo sustituido con 0 - 5 Rᵉ, C₂₋₄ alquinilo sustituido con 0 - 5 Rᵉ, =O, nitro, -(CHRᵈ)ʳS(O)ₚRᶜ, -(CHRᵈ)ʳS(O)ₚNRᵃRᵃ, -(CHRᵈ)ʳNRᵃS(O)ₚRᶜ, -(CHRᵈ)ʳORᵇ, -(CHRᵈ)ʳCN, -(CHRᵈ)ʳNRᵃRᵃ, -(CHRᵈ)ʳNRᵃC(=O)Rᵇ, -(CHRᵈ)ʳNRᵃC(=O)NRᵃRᵃ, -(CHRᵈ)ʳC(=O)ORᵇ, -(CHRᵈ)ʳC(=O)Rᵇ, -(CHRᵈ)ʳOC(=O)Rᵇ, -(CHRᵈ)ʳC(=O)NRᵃRᵃ, -(CHRᵈ)ʳ-cicloalquilo, -(CHRᵈ)ʳ-heterociclilo, -(CHRᵈ)ʳ-arilo y -(CHRᵈ)ʳ-heteroarilo, en donde el alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo se sustituyen con 0 - 4 Rᵉ; alternativamente, dos grupos R⁹ adyacentes se combinan para formar un anillo carbocíclico o heterocíclico que comprende átomos de carbono y 1 - 3 heteroátomos seleccionados de N, O y S(O)ₚ, en donde los anillos carbocíclicos y heterocíclicos se sustituyen con 0 - 4 Rᵉ; Rᵃ, en cada caso, se selecciona independientemente de H, C₁₋₆ alquilo sustituido con 0 - 5 Rᵉ, C₂₋₆ alquenilo sustituido con 0 - 5 Rᵉ, C₂₋₆ alquinilo sustituido con 0 - 5 Rᵉ, -(CH₂)ʳ-C₃₋₁₀ carbociclilo sustituido con 0 - 5 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 5 Rᵉ; o Rᵃ y Rᵃ, junto con el átomo de nitrógeno al que ambos están unidos, forman un anillo heterocíclico sustituido con 0 - 5 Rᵉ; Rᵇ, en cada caso, se selecciona independientemente de H, C₁₋₆ alquilo sustituido con 0 - 5 Rᵉ, C₂₋₆ alquenilo sustituido con 0 - 5 Rᵉ, C₂₋₆ alquinilo sustituido con 0 - 5 Rᵉ, -(CH₂)ʳ-C₃₋₁₀ carbociclilo sustituido con 0 - 5 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 5 Rᵉ; Rᶜ, en cada caso, se selecciona independientemente C₁₋₆ alquilo sustituido con 0 - 5 Rᵉ, C₂₋₆ alquenilo sustituido con 0 - 5 Rᵉ, C₂₋₆ alquinilo sustituido con 0 - 5 Rᵉ, C₃₋₆ carbociclilo y heterociclilo; Rᵈ, en cada caso, se selecciona independientemente de H y C₁₋₆ alquilo sustituido con 0 - 5 Rᵉ; Rᵉ, en cada caso, se selecciona independientemente C₁₋₆ alquilo (opcionalmente sustituido con F, Cl, y Br, OH), C₂₋₆ alquenilo, C₂₋₆ alquinilo, -(CH₂)ʳ-C₃₋₁₀ carbociclilo, -(CH₂)ʳ-heterociclilo, F, Cl, Br, CN, NO₂, =O, CO₂H, CO₂C₁₋₆ alquilo, -(CH₂)ʳOC₁₋₅ alquilo, -(CH₂)ʳOH, -(CH₂)ʳNRᶠRᶠ, -(CH₂)ʳNRᶠRᶠC(=O)C₁₋₄ alquilo, -C(=O)NRᶠRᶠ, -C(=O)Rᶠ, S(O)ₚNRᶠRᶠ, -NRᶠRᶠS(O)ₚC₁₋₄ alquilo y S(O)ₚC₁₋₄ alquilo; Rᶠ, en cada caso, se selecciona independientemente de H, F, Cl, Br, C₁₋₅ alquilo, C₃₋₆ cicloalquilo; o Rᶠ y Rᶠ, junto con el átomo de nitrógeno al que están unidos, forman un anillo heterocíclico; p, en cada caso, se selecciona independientemente de 0, 1 y 2; q, en cada caso, se selecciona independientemente de 0, 1, 2 y 3; r, en cada caso, se selecciona independientemente de 0, 1, 2, 3 y 4; s, en cada caso, se selecciona independientemente de 1 y 2; siempre que s y q se encuentren en el mismo término, s + q £ 3.
ARP140102466A 2013-07-02 2014-07-01 Compuestos tricíclicos de carboxamida como inhibidores potentes de rock AR096788A1 (es)

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EP (1) EP3016951B1 (es)
JP (1) JP6434968B2 (es)
CN (1) CN105492444B (es)
AR (1) AR096788A1 (es)
ES (1) ES2633987T3 (es)
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WO (1) WO2015002915A1 (es)

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