AR072249A1 - Inhibidores de amida hidrolasa de acido graso. usos. metodos. - Google Patents

Inhibidores de amida hidrolasa de acido graso. usos. metodos.

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Publication number
AR072249A1
AR072249A1 ARP090101257A ARP090101257A AR072249A1 AR 072249 A1 AR072249 A1 AR 072249A1 AR P090101257 A ARP090101257 A AR P090101257A AR P090101257 A ARP090101257 A AR P090101257A AR 072249 A1 AR072249 A1 AR 072249A1
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Argentina
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optionally substituted
alkyl
independently
carbocyclyl
aryl
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ARP090101257A
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Infinity Pharmaceuticals Inc
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Publication of AR072249A1 publication Critical patent/AR072249A1/es

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Abstract

Compuestos, y composiciones farmacéuticamente aceptables de ellos, abarcados por cualquiera de las formulas (1), (2), (3), (4), (5) o (6), o sus subgéneros. Métodos para tratar una enfermedad, trastorno o afeccion mediada por FAAH a través de la administracion de una cantidad terapéuticamente efectiva de un compuesto o una composicion que comprende un compuesto de cualquiera de las formulas (1), (2), (3), (4), (5) o (6), o sus subgéneros, a un paciente que lo necesita. Métodos para inhibir FAAH mediante la administracion de una cantidad terapéuticamente efectiva de un compuesto o una composicion que comprende un compuesto de cualquiera de las formulas (1), (2), (3), (4), (5) o (6), o sus subgéneros, a un paciente que lo necesita. Reivindicacion 1: Una composicion farmacéuticamente aceptable que comprende un compuesto de formula (3) o una sal o prodroga farmacéuticamente aceptable de dicho compuesto; en donde: (i) Z1 es -OH o -OR3 y Z2 es -OH, -OR4, un alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, alquinilo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, arilo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; (ii) Z1 y Z2, tomados junto con el átomo de boro al cual están unidos, forman un anillo de 5 a 8 miembros que tiene al menos un átomo de O, S o NR5 directamente unido al átomo de boro; o (iii) Z1 es -OH o -OR3, y Z2 y el Anillo A tomados juntos forman un anillo de 5 a 7 miembros opcionalmente sustituido; W1 y W2 se seleccionan independientemente de CR12, C y N; X es un enlace covalente, -O-, -N=N-, -C=N-, -NR6-, -C(NR6)-, -S-, -C(O)-, -S(O)-, -S(O)2-, o alquileno C1-6 opcionalmente sustituido, en donde una, dos o tres unidades de metileno del alquileno C1-6 están opcional e independientemente reemplazadas por uno o varios grupos seleccionados de -O-, -N=N-, -C=N-, -NR6-, -C(NR6)-, -S-, -C(O)-, -S(O)- y -S(O)2-; RA es hidrogeno, halogeno, -OR7, -CF3, -CN, -NO2, -SO2R7, -SOR7, -C(O)R7, -CO2R7, -C(O)N(R7)2, -N3, -N2R7, -N(R7)2 o el Anillo B que tiene la formula (7) en donde el Anillo B es carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, arilo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R1 es, independientemente, halogeno, -OR8, -CF3, -CN, -NO2, -SO2R8, -SOR8, -C(O)R8, -CO2R8, -C(O)N(R8)2, -N3, -N2R8, -N(R8)2, -B(OH2), alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, alquinilo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, arilo C6-10 opcionalmente sustituido, o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R2 es, independientemente, halogeno, -OR9, -CF3, -CN, -NO2, -SO2R9, -SOR9, -C(O)R9, -CO2R9, -C(O)N(R9)2, -N3, -N2R9, -N(R9)2, alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, alquinilo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, ariIo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R3 y R4 es, independientemente, aIquilo C1-8, opcionalmente sustituido, aIqueniIo C2-8 opcionalmente sustituido, aIquiniIo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, ariIo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcional mente sustituido; cada caso de R5, R6, R7, R8, R9 y R10 es, independientemente, hidrogeno, -SO2R11, -SOR11, -C(O)R11, -CO2R11, -C(O)N(R11)2, -C(O)NH(R1 1), alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, aIquiniIo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, ariIo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R11 es, independientemente, aIquiIo C1-8 opcionalmente sustituido, aIqueniIo C2-8 opcionalmente sustituido, aIquiniIo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, ariIo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R12 es, independientemente, hidrogeno, halogeno, -CF3, alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido o aIquinilo C2-8 opcionalmente sustituido; n es, independientemente, 0, 1, 2 o 3 y m es 0, 1, 2, 3, 4 o 5. Reivindicacion 18: Una composicion farmacéuticamente aceptable que comprende un compuesto de formula (4) o una sal o prodroga farmacéuticamente aceptable de dicho compuesto, en donde: (i) Z1 es -OH o -OR3 y Z2 es -OH, -OR4, un alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, alquinilo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, arilo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; (ii) Z1 y Z2, tomados junto con el átomo de boro al cual están unidos, forman un anillo de 5 a 8 miembros que tiene al menos un átomo de O, S o NR5 directamente unido al átomo de boro; o (iii) Z1 es -OH o -OR3, y Z2 y el Anillo A tomados juntos forman un anillo de 5 a 7 miembros opcionalmente sustituido; Y3, Y4 y Y5 se selecciona cada uno independientemente de C, CR13, N, NR14, O y S, con la condicion de que al menos uno de Y3, Y4 o Y5 sea un heteroátomo seleccionado de N, NR14, O o S; Y6 es C o N; X es un enlace covalente, -O-, -N=N-, -C=N-, -NR6-, -C(NR6)-, -S-, -C(O)-, -S(O)-, -S(O)2-, o alquileno C1-6 opcionalmente sustituido, en donde una, dos o tres unidades de metileno del alquileno C1-6 están opcional e independientemente reemplazadas con uno o varios grupos seleccionados de -O-, -N=N-, -C=N-, -NR6-, -C(NR6)-, -S-, -C(O)-, -S(O)-, -S(O)2-, Ra es hidrogeno, halogeno, -OR7, -CF3, -CN, -NO2, -SO2R7, -SOR7, - C(O)R7, -CO2R7, -C(O)N(R7)2, -CHO, -N3, -N2R7, -N(R7)2, o el Anillo B que tiene la formula (7) en donde el Anillo B es carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, ariIo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R1 es, independientemente, halogeno, -OR8, -CF3, -CN, -NO2, -SO2R8, -SOR8, -C(O)R8, -CO2R8, -C(O)N(R8)2, -N3, -N2R8, -N(R8)2, -B(OH2), alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, alquinilo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, arilo C6-10 opcionalmente sustituido, o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R2 es, independientemente, halogeno, -OR9, -CF3, -CN, -NO2, -SO2R9, -SOR9, -C(O)R9, -CO2R9, -C(O)N(R9)2, -N3, -N2R9, -N(R9)2, alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, alquinilo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, ariIo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R3 y R4 es, independientemente, aIquilo C1-8, opcionalmente sustituido, aIqueniIo C2-8 opcionalmente sustituido, aIquiniIo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, ariIo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcional mente sustituido; cada caso de R5, R6, R7, R8, R9, R10 y R14 es, independientemente, hidrogeno, -SO2R11, -SOR11, -C(O)R11, -CO2R11, -C(O)N(R11)2, -C(O)NH(R1 1), alquilo C1-8 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, aIquiniIo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, heteroalquenilo C2-8 opcionalmente sustituido, heteroalquinilo C2-8 opcionalmente sustituido, carbociclilo C3-10 opcionalmente sustituido, heterociclilo de 3-10 miembros opcionalmente sustituido, ariIo C6-10 opcionalmente sustituido o heteroarilo de 5-10 miembros opcionalmente sustituido; cada caso de R11 es, independientemente, aIquiIo C1-8 opcionalmente sustituido, aIqueniIo C2-8 opcionalmente sustituido, aIquiniIo C2-8 opcionalmente sustituido, heteroalquilo C1-8 opcionalmente sustituido, h
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CN102046179B (zh) 2015-01-14
US20150368278A1 (en) 2015-12-24
PE20091838A1 (es) 2009-12-18
TW201000107A (en) 2010-01-01
JP2011516564A (ja) 2011-05-26
IL208536A0 (en) 2010-12-30
EP2282742A1 (en) 2011-02-16
JP5637982B2 (ja) 2014-12-10
CL2009000870A1 (es) 2010-06-25
AU2009233711A1 (en) 2009-10-15
CN102046179A (zh) 2011-05-04
CA2721060A1 (en) 2009-10-15

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