AR092349A1 - Imidazotriazincarbonitrilos utiles como inhibidores de quinasa - Google Patents

Imidazotriazincarbonitrilos utiles como inhibidores de quinasa

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Publication number
AR092349A1
AR092349A1 ARP130102495A ARP130102495A AR092349A1 AR 092349 A1 AR092349 A1 AR 092349A1 AR P130102495 A ARP130102495 A AR P130102495A AR P130102495 A ARP130102495 A AR P130102495A AR 092349 A1 AR092349 A1 AR 092349A1
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Argentina
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crgrg
substituted
alkyl
group
independently selected
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ARP130102495A
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N Huynh Tram
Mastalerz Harold
Zhang Guifen
Vinayak Purandare Ashok
Zimmerman Kurt
Zhao Yufen
Lewis Johnson Walter
C Hart Amy
He Liqi
Vaccaro Wayne
M Tarby Christine
E Fink Brian
Zhang Yong
Chen Libing
Chen Bin
S Tokarski John
Inghrim Jennifer
Sang Xiaopeng
Wan Honghe
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Bristol Myers Squibb Co
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Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of AR092349A1 publication Critical patent/AR092349A1/es

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Abstract

Estas imidazotriazinas inhiben la actividad de la proteína quinasa, lo cual las vuelve útiles como agentes antineoplásicos. Reivindicación 1: Un compuesto caracterizado por la fórmula (1), o una sal de este aceptable desde el punto de vista farmacéutico, en donde R¹ se selecciona del grupo que consiste en H, F, Cl, Br, CN y alquilo C₁₋₆; R² se selecciona del grupo que consiste en arilo sustituido con 1 - 5 R⁶ y heteroarilo sustituido con 1 - 5 R⁶; R³ se selecciona del grupo que consiste en hidrógeno y alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ; opcionalmente, R² y R³, junto con el átomo de nitrógeno al que están unidos, forman un anillo heterocíclico sustituido con 1 - 5 R⁶; R⁴ se selecciona del grupo que consiste en H, alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ, -(CH₂)ʳORᵇ, -(CH₂)ʳS(O)ₚRᶜ, -(CH₂)ʳC(=O)Rᵈ, -(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳC(=O)NRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)Rᵈ, -(CH₂)ʳNRᵃC(=O)ORᵇ, -(CH₂)ʳOC(=O)NRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)ORᵇ, -(CH₂)ʳS(O)₂NRᵃRᵃ, -(CH₂)ʳNRᵃS(O)₂NRᵃRᵃ, -(CH₂)ʳNRᵃS(O)₂Rᶜ, -(CH₂)ʳ-carbociclilo C₃₋₁₀ sustituido con 1 - 5 Rᵉ, (CH₂)ʳ-heterociclilo sustituido con 1 - 5 Rᵉ; R⁵ se selecciona del grupo que consiste en H y alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ; R⁶, en cada caso, se selecciona independientemente del grupo que consiste en H, F, Cl, Br, CN, -(CRᵍRᵍ)ʳNR⁷R⁷, NO₂, -ORᵇ, -C(=O)NR⁷R⁷, -C(=O)Rᵇ, -NRᵃC(=O)ORᵇ, -NRᵃC(=O)(CRᵍRᵍ)ʳNRᵃRᵃ, alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ, alquenilo C₂₋₄ sustituido con 1 - 5 Rᵉ, -(CRᵍRᵍ)ʳ-carbociclo C₃₋₆ sustituido con 1 - 5 R⁸ y -(CRᵍRᵍ)ʳ-heterociclilo sustituido con 1 - 5 R⁸; o dos grupos R⁶ adyacentes se toman junto con los átomos del anillo al que están unidos para formar un heterociclilo o carbociclilo fusionado, cada uno sustituido con 1 - 5 R⁸; R⁷, en cada caso, se selecciona independientemente del grupo que consiste en H, alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ, -(CH₂)ʳ-carbociclilo C₃₋₁₀ sustituido con 1 - 5 R⁸ y - (CH₂)ʳ-heterociclilo sustituido con 1 - 5 R⁸; o R⁷ y R⁷, junto con el átomo de nitrógeno al que están unidos, forman un anillo heterocíclico sustituido con 1 - 5 R⁸; R⁸, en cada caso, se selecciona independientemente del grupo que consiste en H, F, Cl, Br, alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ, alquenilo C₂₋₆ sustituido con 1 - 5 Rᵉ, alquinilo C₂₋₆ sustituido con 1 - 5 Rᵉ, =O, -(CRᵍRᵍ)ʳORᵇ, -(CRᵍRᵍ)ʳS(O)ₚRᶜ, -(CRᵍRᵍ)ʳC(=O)(CRᵍRᵍ)ʳRᵈ, -(CRᵍRᵍ)ʳNRᵃRᵃ, -(CRᵍRᵍ)ʳC(=O)NRᵃRᵃ, -(CRᵍRᵍ)ʳC(=O)NRᵃS(O)ₚRᶜ, -(CRᵍRᵍ)ʳNRᵃ(CRᵍRᵍ)ʳC(=O)Rᵈ, -(CRᵍRᵍ)ʳNRᵃC(=O)ORᵇ, -(CRᵍRᵍ)ʳOC(=O)(CRᵍRᵍ)ʳRᵈ, -(CRᵍRᵍ)ʳOC(=O)(CRᵍRᵍ)ʳ(=O)ORᵈ, -(CRᵍRᵍ)ʳOC(=O)(CRᵍRᵍ)ʳC(=O)ʳRᵈ, -(CRᵍRᵍ)ʳOC(=O)(CRᵍRᵍ)ʳNRᵃC(=O)Rᵇ, -(CRᵍRᵍ)ʳOC(=O)(CRᵍRᵍ)ʳNRᵃRᵃ, -(CRᵍRᵍ)ʳNRᵃ(CRᵍRᵍ)ʳC(=O)NRᵃRᵃ, -(CRᵍRᵍ)ʳC(=O)(CH₂)ʳORᵇ, -(CRᵍRᵍ)ʳC(=O)(CRᵍRᵍ)ʳOC(=O)Rᵇ, -(CRᵍRᵍ)ʳS(O)₂NRᵃRᵃ, -(CRᵍRᵍ)ʳNRᵃS(O)ₚ-NRᵃRᵃ, -(CRᵍRᵍ)ʳNRᵃS(O)ₚRᶜ, -OPO₃H, -(CRᵍRᵍ)NRᵃC(=O)O(CRᵍRᵍ)ʳO(CRᵍRᵍ)ʳO(CRᵍRᵍ)ʳO(CRᵍRᵍ)ʳO(CRᵍRᵍ)ʳO(CRᵍRᵍ)ʳO-alquilo C₁₋₄, -(CRᵍRᵍ)ʳ-carbociclilo C₃₋₁₀ sustituido con 1 - 5 Rᵉ y -(CRᵍRᵍ)ʳ-heterociclilo sustituido con 1 - 5 Rᵉ; Rᵃ, en cada caso, se selecciona independientemente del grupo que consiste en H, CN, alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ, alquenilo C₂₋₆ sustituido con 1 - 5 Rᵉ, alquinilo C₂₋₆ sustituido con 1 - 5 Rᵉ, (CH₂)ʳ-carbociclilo C₃₋₁₀ sustituido con 1 - 5 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 1 - 5 Rᵉ; o Rᵃ y Rᵃ, junto con el átomo de nitrógeno al que están unidos, forman un anillo heterocíclico sustituido con 1 - 5 Rᵉ; Rᵇ, en cada caso, se selecciona independientemente del grupo que consiste en H, alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ, alquenilo C₂₋₆ sustituido con 1 - 5 Rᵉ, alquinilo C₂₋₆ sustituido con 1 - 5 Rᵉ, (CH₂)ʳ-carbociclilo C₃₋₁₀ sustituido con 1 - 5 Rᵉ y - (CH₂)ʳ-heterociclilo sustituido con 1 - 5 Rᵉ; Rᶜ, en cada caso, se selecciona independientemente del grupo que consiste en alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ, alquenilo C₂₋₆ sustituido con 1 - 5 Rᵉ, alquinilo C₂₋₆ sustituido con 1 - 5 Rᵉ, carbociclilo C₃₋₆ y heterociclilo; Rᵈ, en cada caso, se selecciona independientemente del grupo que consiste en H, OH, alquilo C₁₋₆ sustituido con 1 - 5 Rᵉ, alquenilo C₂₋₆ sustituido con 1 - 5 Rᵉ, alquinilo C₂₋₆ sustituido con 1 - 5 Rᵉ, (CH₂)ʳ-carbociclilo C₃₋₁₀ sustituido con 1 - 5 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 1 - 5 Rᵉ; Rᵉ, en cada caso, se selecciona independientemente del grupo que consiste en H, N₃, alquilo C₁₋₆ sustituido con 1 - 5 Rᶠ, alquenilo C₂₋₆, alquinilo C₂₋₆, (CH₂)ʳ-cicloalquilo C₃₋₆, -(CH₂)ʳ-heterociclilo, F, Cl, Br, -(CH₂)ʳCN, NO₂, =O, OPO₃H, -OSi(alquilo C₁₋₄)₃, -(CH₂)ʳO-alquilo C₁₋₅, -(CH₂)ʳO(CH₂)ʳO-alquilo C₁₋₅, -(CH₂)ʳOH, -(CH₂)ʳS(O)₂-alquilo C₁₋₅, (CH₂)ʳS(O)₂Rᶠ, -(CH₂)ʳNHS(O)₂-alquilo C₁₋₅, -S(O)₂NH₂, SH, -(CH₂)ʳNRᶠRᶠ, (CH₂)ʳNHC(=O)ORᶠ, (CH₂)ʳNHC(=O)Rᶠ, -(CH₂)ʳNHC(=NH)NRᶠRᶠ, (CH₂)ʳC(=O)(CH₂)NRᶠRᶠ y (CH₂)ʳC(=O)ORᶠ; Rᶠ, en cada caso, se selecciona independientemente del grupo que consiste en H, -(CH₂)ʳOH, -(CH₂)O-alquilo C₁₋₅, alquilo C₁₋₅ (opcionalmente sustituido con F, Cl, OH, NH₂), cicloalquilo C₃₋₆ opcionalmente sustituido con NH₂, -(CH₂)ʳS(O)ₚ-alquilo C₁₋₄, -NHC(=O)alquilo C₁₋₅, -C(=O)NH₂, -C(=O)O-alquilo C₁₋₄, -C(=O)alquilo C₁₋₄, -(CH₂)ʳ-fenilo, -(CH₂)ʳ-heterociclilo opcionalmente sustituido con alquilo y CN, o Rᶠ y Rᶠ, junto con el átomo de nitrógeno al que están unidos, forman un anillo heterocíclico opcionalmente sustituido con alquilo C₁₋₄; Rᵍ, en cada caso, se selecciona independientemente del grupo que consiste en H, F, OH y alquilo C₁₋₅; p, en cada caso, se selecciona independientemente del grupo que consiste en 0, 1 y 2; y r, en cada caso, se selecciona independientemente del grupo que consiste en 0, 1, 2, 3, 4 y 5.
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