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AR059246A1 - Compuestos heterobiciclicos de tiofeno y metodos de uso - Google Patents

Compuestos heterobiciclicos de tiofeno y metodos de uso

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Publication number
AR059246A1
AR059246A1 ARP070100391A ARP070100391A AR059246A1 AR 059246 A1 AR059246 A1 AR 059246A1 AR P070100391 A ARP070100391 A AR P070100391A AR P070100391 A ARP070100391 A AR P070100391A AR 059246 A1 AR059246 A1 AR 059246A1
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AR
Argentina
Prior art keywords
nr10r11
aryl
alkyl
cr14r15
heteroaryl
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Application number
ARP070100391A
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English (en)
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Array Biopharma Inc
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Publication of AR059246A1 publication Critical patent/AR059246A1/es

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    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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    • 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

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Abstract

Compuesto de formula (1) y sus sales farmacéuticamente aceptables, que son utiles para inhibir las quirosin quinasas receptoras y para tratar trastornos intermediados por éstas. Se describen métodos de uso de los compuestos de formula (1) y sus sales farmacéuticamente aceptables para el diagnostico, prevencion o tratamiento in vitro, in situ e in vivo de dichos trastornos en células de mamíferos o trastornos patologicos asociados. Reivindicacion 1: Un compuesto seleccionado de la formula (1), y sus sales farmacéuticamente aceptables, donde: X es O, S o NR10; Z2 y Z3 están independientemente seleccionados entre CR4 y N, donde unicamente uno de Z2 y Z3 es N; R1 es H, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, -C(=O)NR10R11, N- (CR14R15)tNR10R11, -NR10C(=Y)R11, -NR10C(=Y)OR11, -NR12C(=Y)NR10R11, o -NR12SO2NR10R11, o R1 es un carbociclilo C3-12, heterociclilo C2-20, arilo C6-20 o heteroarilo C1-20 monocíclico o bicíclico, donde dichos alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo y heteroarilo están sustituidos opcionalmente con uno o más grupos seleccionados independientemente entre F, CI, Br, I, CN, CF3, oxo, OR10, SR10, -C(=Y)R10, -C(=Y)OR10, -C(=Y)NR10R11, -(CR14R15)n-NR10R11, - NR10C(=Y)R13, -NR10C(=Y)OR11, --NR12C(=Y)NR10R11, -NR12SO2R10, -OC(=Y)R10, -OC(=Y)OR10, -OC(=Y)NR10R11, -OS(O)2(OR10), -OP(=Y)(OR10)(OR11), -OP(OR10)(OR11), -S(O)R10, -S(O)2R10, -S(O)2NR10R11, -S(O)(OR10), -S(O)2(OR10), -SC(=Y)R10, -SC(=Y)OR10, - SC(=Y)NR10R11, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, cicloalquilo C3-12, heterociclilo C2-20, arilo C6-20 y heteroarilo C1-20, -(CR14R15)n-NR12C(=O)(CR14R15)mNR10R11, y -C(O)(CR14R15)nNR10R11; R2 y R4 son independientemente H, F, CI, Br, I, CN, -C(=Y)R10, -C(=Y)OR10, -C(=Y)NR10R11, -NR10R11, -NR10C(=Y)R11, -NR10C(=Y)OR11, -NR12C(=Y)NR10R11, -NR12SO2R10R11, -OR10, -OC(=Y)R10, -OC(=Y)OR10, -OC(=Y)NR10R11, -C(=O)NR12(CR14R15)tNR10R11, -OP(=Y)(OR10)(OR11), -OP(OR10)(OR11), -SR10, -S(O)R10, -S(O)2R10, -S(O)2NR10R11, -SC(=Y)R10, -SC(=Y)OR10, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo C3-12, heterociclilo C2-20, arilo C6-20, o heteroarilo C1-20, donde dichos alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo están sustituidos opcionalmente con uno o más grupos seleccionados independientemente entre F, CI, Br, I, OR10, y NR10R11; R3 es un carbociclilo C3-12, heterociclilo C2-20, arilo C6-20 o heteroarilo C1-20 monocíclicos o bicíclicos, donde dichos carbociclilo, heterociclilo, arilo y heteroarilo están sustituidos opcionalmente con uno o más grupos seleccionados independientemente entre F, CI, Br, I, CN, CF3, OR10, SR10, -C(=Y)R10, -C(=Y)OR10, -C(=Y)NR10R11, -NR10R11, - NR10C(=Y)R13, -NR10C(=Y)OR11, -NR12C(=Y)NR10R11, -NR12C(=Y)NR10R11, -NR12C(=O)C(=O)R10R11, -NR12C(=O)C(=O)NR10R11, -NR12C(=O)C(=O)Ora, -NR12SO2R10, -NR12C(=Y1)(CR14R15)nC(=Y2)NR10R11, -NR12C(=Y1)NR10C(=Y2)(CR14R15)nR11, - NR12C(=Y1)(CR14R15)nC(=Y2)(CR14R15)mR10, -OC(=Y)R10, -OC(=Y)OR10, -OC(=Y)NR10R11, -OS(O)2(OR10), -OP(=Y)(OR10)(OR11), -OP(OR10)(OR11), -S(O)R10, -S(O)2R10, -S(O)2NR10R11, -S(O)(OR10), -S(O)2(OR10), -SC(=Y)R10, -SC(=Y)OR10, -SC(=Y)NR10R11, alquilo C1- 12, alquenilo C2-8, alquinilo C2-8, cicloalquilo C3-12, heterociclilo C2-20, arilo C6-20 y heteroarilo C1-20, donde dichos alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo, y heteroarilo están sustituidos opcionalmente con uno o más grupos seleccionados independientemente entre F, CI, Br, I, OH, alquilo C1-12, oxo, NR10R11, -C(=Y)NR10R11 y(CR14R15)n-arilo; R10, R11 y R12 son independientemente H, ORa, alquilo C1-12, alquenilo C2-8, o alquinilo C2-8, o carbociclilo C3-12, heterociclilo C2-20, arilo C6-20, o heteroarilo C1-20 monocíclicos o bicíclicos donde dichos alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo están sustituidos opcionalmente con uno o más grupos seleccionados independientemente entre F, CI, Br, I, SO2RC, CN, ORa, NRaRb, C(=O)NRaRb, CRaC(=O)Rb, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo C3-20, arilo C6-20, y heteroarilo C1-20, o R10 y R11 conjuntamente con el nitrogeno al cual están unidos forman opcionalmente un anillo heterocíclico C3-20 saturado, parcialmente insaturado o totalmente insaturado que contiene opcionalmente uno o más átomos de anillos adicionales seleccionados entre N, O o S, donde dicho anillo heterocíclico está sustituido opcionalmente con uno o más grupos seleccionados independientemente entre oxo, ORa NRaRb, CF3, F, CI, Br, I, SO2Ra, C(=O)Ra, NR10C(=Y)R11, C(=Y)NR10R11, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, cicloalquilo C3-12, heterociclilo C2-20, arilo C6-20 y heteroarilo C1-20, R13 es H, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, (CR14R15)n-cicloalquilo, -(CR14R15)n-heterocicliIo, (CR14R15)n-arilo, (CR14R15)n-heteroarilo, (CR14R15)n-O-(CR14R15)m-arilo, (CR14R15)n-OR10, (CR14R15)n- NR10R11, (CR14R15)n-NR10C(=O)R11, o (CR14R15)n-NR10(SO2Me)-R11, donde dichas porciones alquilo, alquenilo, alquinilo, cicloalquilo, heterocicloalquilo, y heteroarilo están sustituidas opcionalmente con uno o más grupos seleccionados independientemente entre F, CI, Br, I, oxo, SO2RC, CN, ORa, C(=O)Ra, C(=O)ORa, NRaRb, NRaC(=O)Rb, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, cicloalquilo C3-12, heterociclilo C2-20, arilo C6-20, y heteroarilo C1-20; R14 y R15 son independientemente H, alquilo C1-12, o (CR14R15)tariIo, o R14 y R15 conjuntamente con los átomos a los cuales están unidos forman un anillo carbocíclico C3-12 saturado o parcialmente insaturado; o R10 y R15 conjuntamente con los átomos a los cuales están unidos forman un anillo heterocíclico C1-20 saturado o parcialmente insaturado que está opcionalmente sustituido con uno o más grupos seleccionados independientemente entre F, CI, Br, I, ORa, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, cicloalquilo C3-12, heterociclilo C2-20, arilo C6-20, y heteroarilo C1-20, donde dichos alquilo y arilo están sustituidos opcionalmente con uno o más grupos seleccionados independientemente entre F, CI, Br, y I, o R14 es nulo y R10 y R15 conjuntamente con los átomos a los cuales están unidos forman un anillo heteroarilo C1-20 que tiene uno o más heteroátomos; Ra y Rb son independientemente H, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo C3-12, heterociclilo C2-20, arilo C6-20, o heteroarilo C1-20, donde dichos alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo, y heteroarilo están sustituidos opcionalmente con uno o más grupos alquilo o halogeno; Rc es alquilo C1-12 o arilo C6-20, donde dichos alquilo y arilo están sustituidos opcionalmente con uno o más grupos seleccionados independientemente entre F, CI, Br, I, ORa y C(=O)NRaRb; Y, Y1 y Y2 son independientemente O o S; t es 1,2,3,4,5 o 6;y n y m son independientemente 0, 1, 2, 3, 4, 5 o 6.
ARP070100391A 2006-01-30 2007-01-30 Compuestos heterobiciclicos de tiofeno y metodos de uso AR059246A1 (es)

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US (1) US8003662B2 (es)
EP (1) EP1989211A2 (es)
JP (1) JP2009526761A (es)
CN (1) CN101522687A (es)
AR (1) AR059246A1 (es)
CA (1) CA2636242A1 (es)
TW (1) TW200806675A (es)
WO (1) WO2008063202A2 (es)

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