AR038612A1 - Composiciones y metodos para el tratamiento de enfermedades del tejido epitelial y retinal - Google Patents

Composiciones y metodos para el tratamiento de enfermedades del tejido epitelial y retinal

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AR038612A1
AR038612A1 ARP030100650A ARP030100650A AR038612A1 AR 038612 A1 AR038612 A1 AR 038612A1 AR P030100650 A ARP030100650 A AR P030100650A AR P030100650 A ARP030100650 A AR P030100650A AR 038612 A1 AR038612 A1 AR 038612A1
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substituted
aryl
alkyl
aralkyl
oxygen
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Inspire Pharmaceuticals Inc
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Abstract

La presente se refiere a compuestos mononucleósido fosfatos que tienen los beneficios de un dinucleótido farmacéutico. Estos mononucleósido fosfatos pueden producirse a partir de un mononucleótido que ha sido modificado por la adhesión de un sustituyente resistente a la degradación en el terminal fosfato de un mononucleótido polifosfato. Al adherir este sustituyente resistente a la degradación, la estabilidad de la degradación se equipara ó excede de las de ciertos di nucleótidos. Reivindicación 1: Un compuesto de fórmula (1), ó una sal farmacéuticamente aceptable del mismo. A es un sustituyente covalentemente ligado que tiene un peso molecular máximo de 1000 y está seleccionado a partir del grupo que consiste de un aminoácido, un péptido, un polipéptido, un oligonucleótido, un esteroide natural ó no natural, OR1, SR1, NR1R2 y CR1R2R3, en donde R1, R2 y R3 son cada uno independientemente hidrógeno, alquilo, cicloalquilo, arilo, arilalquilo, fosfonato, ó aciltioalquilo, con ó sin sustituyentes o heteroátomos; ó tomados juntos para formar un anillo cicloalquilo ó arilo, con ó sin sustituyentes o heteroátomos, con la excepción de que OR1 y SR1 no sean OH o SH; X1, X2 y X3 son independientemente oxígeno, metileno, monoclorometileno, diclorometileno, monofluormetileno, difluormetileno, ó imido; T1, T2, W y V son independientemente oxígeno o azufre; m = 0, 1 ó 2; n = 0 o 1; p = 0, 1 ó 2; donde la suma de m + n + p es de 0 a 5; M = H ó un contraión inorgánico u orgánico farmacéuticamente aceptable; D = O ó CH2; B es un residuo purina o pirimidina de acuerdo con las fórmulas generales (4) y (5) que está unido a la posición 1' de la furanosa ó el carbociclo mediante la posición 9- ó 1- de la base, respectivamente; Y = H, OH, u OR4; Z = H, OH, ó OR5; con la condición de que Y y Z no sean ambos H; R4 y R5 son residuos que están unidos directamente a los oxígenos 2' y/o 3' de la furanosa ó el carbociclo mediante un átomo de carbono de acuerdo con la fórmula (2), ó unidos directamente a los dos oxígenos 2' y 3' de la furanosa ó el carbociclo mediante un átomo de carbono común de acuerdo con la fórmula (3); fórmula (2) en donde O es el correspondiente oxígeno 2' y/o 3' de la furanosa o el carbociclo; C es el átomo de carbono; R6, R7 y R8 son H, un alquilo, cicloalquilo, aralquilo, arilo, aralquilo sustituido, ó arilo sustituido, de modo que la porción definida de acuerdo con la fórmula (2) es un éter; ó R6 y R7 son H, un alquilo, cicloalquilo, aralquilo, arilo, aralquilo sustituido, ó arilo sustituido, y R8 es alcoxi, cicloalcoxi, aralquiloxi, ariloxi, aralquiloxi sustituido , ó ariloxi sustituido de modo que la porción definida de acuerdo con la fórmula (2) es un acetal o cetal acíclico; ó R6 y R7 son tomados juntos como oxígeno o azufre doblemente unidos a C, y R8 es alquilo, cicloalquilo, aralquilo, arilo, aralquilo sustituido, o arilo sustituido, de modo que la porción definida de acuerdo con la fórmula (2) es un éster o tioéster; ó R6 y R7 son tomados juntos como oxígeno o azufre doblemente unidos a C, y R8 es amino o amino mono- o disustituido, donde los sustituyentes son alquilo, cicloalquilo, aralquilo, arilo, aralquilo sustituido, o arilo sustituido, de modo que la porción de acuerdo con la fórmula (2) es un carbamato o tiocarbamato, ó R6 y R7 son tomados juntos como oxígeno o azufre doblemente unidos a C, y R8 es alcoxi, cicloalcoxi, aralquiloxi, ariloxi, aralquiloxi sustituido, o ariloxi sustituido de modo que la porción de acuerdo con la fórmula (2) es un carbonato ó tiocarbonato; ó R8 no está presente y R6 y R7 son tomados juntos como oxígeno o azufre doblemente ligado a C y ambos oxígeno 2' y 3' de la furanosa están directamente ligados a C para formar un carbonato o tiocarbonato cíclico; fórmula (3) en donde: O es los oxígenos 2' y 3' de la furanosa o carbociclo; y los oxígenos 2' y 3' de la furanosa o carbociclo están unidos por un átomo de carbono común ( C) para formar un acetal cíclico, cetal cíclico u ortoéster cíclico; para los acetales y cetales cíclicos, R9 y R10 son independientemente hidrógeno, alquilo, cicloalquilo, aralquilo, arilo, aralquilo sustituido, ó pueden estar unidos para formar un anillo homocíclico o heterocíclico compuesto de 3 a 8 átomos, preferentemente 3 a 6 átomos, para los ortoésteres cíclicos, R9 es hidrógeno, alquilo, cicloalquilo, aralquilo, arilo, aralquilo sustituido ó arilo sustituido; R10 es alquiloxi, cicloalquiloxi, aralquiloxi, ariloxi, aralquiloxi sustituido, o ariloxi sustituido, fórmula (4),fórmula (5) en donde: R11 y R15 son hidroxi, oxo, amino, mercapto, alquiltio, ariltio, alquiloxi, ariloxi, alquilamino, cicloalquilamino, aralquilamino, arilamino, diaralquilamino, diarilamino, ó dialquilamino, donde los grupos alquilo son opcionalmente ligados para formar un heterociclo; ó R11 y R15 son acilamino, siempre que incorporen un residuo amino a partir de la posición C-6 de la purina o la posición C-4 de la pirimidina; ó cuando R11 en una purina ó R15 en una pirimidina tiene como su primer átomo nitrógeno, R11 y R12 ó R15 y R16 son tomados juntos para formar un anillo imidazol fusionado de 5 miembros, opcionalmente sustituidos en el anillo eteno con porciones alquilo, cicloalquilo, aralquilo, ó arilo, según lo descripto para R6-R10 anterior; cuando R15 en una pirimidina tiene como su primer átomo oxígeno, R15 y R17 son tomados juntos para formar un anillo dihidrofurano de 5 miembros, opcionalmente sustituido en el anillo dihidrofurano con porciones alquilo, cicloalquilo, aralquilo ó arilo, según lo descripto para R6-R10 anterior; J es carbono o nitrógeno, con la condición de que cuando es nitrógeno R13 no está presente; R12 es hidrógeno, o está ausente; R16 es hidrógeno o acilo; R13 es hidrógeno, alquilo, bromo, azido, alquilamino, arilamino ó aralquilamino, alcoxi, ariloxi ó aralquiloxi, alquiltio, ariltio o aralquiltio, ó omega-E(alquilo C1-6)G-, donde E y G son independientemente amino, mercapto, hidroxi o carboxilo; R14 es hidrógeno, halo, amino, amino monosustituido, amino disustituido, alquiltio, ariltio o aralquiltio, donde el sustituyente en el azufre contiene hasta un máximo de 20 átomos de carbono, con o sin insaturación; R17 es hidrógeno, metilo, alquilo, halo, alquilo, alquenilo, alquenilo sustituido, alquinilo ó alquinilo sustituido.
ARP030100650A 2002-02-27 2003-02-27 Composiciones y metodos para el tratamiento de enfermedades del tejido epitelial y retinal AR038612A1 (es)

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US (1) US7115585B2 (es)
EP (2) EP1545555A4 (es)
JP (1) JP4745610B2 (es)
KR (1) KR100990346B1 (es)
CN (1) CN1671398A (es)
AR (1) AR038612A1 (es)
AU (1) AU2003223225B2 (es)
BR (1) BR0307783A (es)
CA (1) CA2477241C (es)
MX (1) MXPA04008293A (es)
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EP1545555A4 (en) 2010-09-29
KR100990346B1 (ko) 2010-10-29
CA2477241C (en) 2012-04-10
CA2477241A1 (en) 2003-09-04
US7115585B2 (en) 2006-10-03
KR20040094736A (ko) 2004-11-10
BR0307783A (pt) 2005-09-13
WO2003072067A2 (en) 2003-09-04
WO2003072067A3 (en) 2005-04-28
US20030008834A1 (en) 2003-01-09
AU2003223225A1 (en) 2003-09-09
JP2005526046A (ja) 2005-09-02
EP1545555A2 (en) 2005-06-29
AU2003223225B2 (en) 2007-02-22
EP2647382A1 (en) 2013-10-09
JP4745610B2 (ja) 2011-08-10

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