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AR066143A2 - Composiciones y combinaciones terapeuticas deinhibidor (es) de absorcion de esterol con agente (s) cardiovascular (es) y el uso de las mismas para la preparacion de medicamentos para el tratamiento de afecciones vasculares - Google Patents

Composiciones y combinaciones terapeuticas deinhibidor (es) de absorcion de esterol con agente (s) cardiovascular (es) y el uso de las mismas para la preparacion de medicamentos para el tratamiento de afecciones vasculares

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Publication number
AR066143A2
AR066143A2 ARP080100736A ARP080100736A AR066143A2 AR 066143 A2 AR066143 A2 AR 066143A2 AR P080100736 A ARP080100736 A AR P080100736A AR P080100736 A ARP080100736 A AR P080100736A AR 066143 A2 AR066143 A2 AR 066143A2
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Schering Corp
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P3/00—Drugs for disorders of the metabolism
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    • A—HUMAN NECESSITIES
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    • A61P9/00—Drugs for disorders of the cardiovascular system
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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Abstract

Reivindicacion 1: Una composicion caracterizada porque comprende, (i) al menos un inhibidor de absorcion de esterol o su aceptable para uso farmacéutico; y (ii) al menos un agente cardiovascular para el tratamiento de afecciones cardiovasculares que es diferente de al menos un inhibidor de absorcion de esterol; donde el al menos un inhibidor de absorcion de esterol representado por (a) formula (1) o sus isomeros, o sales o solvatos aceptables para uso farmacéutico de los compuestos de la de la formula (1) o de sus isomeros, o prodrogas de los compuestos de la formula (1) o de sus isomeros, sales o solvatos, en los que, en la formula (1) anterior: Ar1 es arilo R3-sustituido; Ar2 es arilo R4-sustituido; Ar3 es arilo R5-sustituido; Y y Z se seleccionan de manera independiente del grupo que se encuentra conformado por -CH2-, -CH(alquilo inferior)- y -C-(dialquilo inferior)-A se selecciona de -O-, -S-. -S(O)- o -S(O)2; R1 se selecciona del grupo que se encuentra conformado por -O(CO)R6, -O(CO)OR9 y -O(CO)NR6R7; R2 se selecciona del grupo que se encuentra conformado por hidrogeno, alquilo inferior, y arilo; o R1 y R2 juntos son =O; q es 1, 2, o 3; p es 0, 1, 2, 3 o 4; R5 es sustituyentes 1-3 que se seleccionan de manera independiente del grupo que se encuentra conformado por -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR9, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2-alquilo inferior, NR6SO2-arilo-, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2arilo, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, o-halogeno, m-halogeno, o-alquilo inferior, m-alquilo inferior, -(alquileno inferior)-COOR6, y -CH=CH-COOR6; R3 y R4 son de manera independiente sustituyentes 1-3 que se seleccionan de manera independiente del grupo que se encuentra conformado por hidrogeno, p-alquilo inferior, arilo, -NO2, -CF3 y p-halogeno; R6, R7 y R8 se seleccionan de manera independiente del grupo que se encuentra conformado por hidrogeno, alquilo inferior, arilo y alquilo inferior de arilo-sustituido; y R9 es alquilo inferior, arilo o alquilo inferior de arilo-sustituido; (b) formula (2) o isomeros de los compuestos de la formula (2), o sales o solvatos que son aceptables para uso farmacéutico de los compuestos de la formula (2) o de los isomeros de los compuestos de la formula (2), o prodrogas de los compuestos de la formula (2) o de los isomeros, sales o solvatos de los compuestos de la formula (2), en los que, en la formula (2) anterior: A se selecciona del grupo que se encuentra conformado por heterocicloalquilo R2-sustituido, heteroarilo R2-sustituido, heterocicloalquilo benzofusionado R2-sustituido, y heteroarilo benzofusionado R2-sustituido; Ar1 es arilo R3-sustituido; Ar2 es arilo R4-sustituido; Q es un enlace o, con el carbono de anillo de posicion 3 de la azetidinona, forma el grupo espiro de formula (3); y R1 se selecciona del grupo que se encuentra conformado por: (CH2)q, en el que q es de 2 a 6, siempre que cuando Q forme un anillo espiro, q también pueda ser cero o 1; -(CH2)e-G-(CH2)r-, en la que G es -O-, -C(O)-, fenileno, -NR8 o S(O)0-2, e es 0-5 y r es 0-5, siempre que la suma de e y r sea 1-6; -(alquenileno C2-6) y -(CH2)f-V-(CH2)g- en el que V es cicloalquileno C3-6, f es 1-5 y g es 0-5, siempre que la suma de f y g sea 1-6; R5 se selecciona de: >CH-, >C-(alquil C1-6 )-, >CF-, >C(OH)-, >C(C6H4-R9)-, >N-, o s+NO--; R6 y R7 se seleccionan de manera independiente del grupo que se encuentra conformado por -CH2, -CH(alquilo C1-6)-, -C(di-alquilo C1-6)-, -CH=CH- y -C(alquilo C1-6)=CH-; o R5 junto con R6 adyacente, o R5 junto con un R7 adyacente, forman un grupo -CH=CH- o un -CH=C(alquilo C1-6)-: a y b son de manera independiente 0, 1, 2, o 3, siempre que los dos no sean cero; siempre que cuando R6 sea -CH=CH- o -C(alquilo C1-6)=CH-, a es 1; siempre que cuando R7 sea -CH=CH- o -C(alquilo C1-6)=CH-, b es 1; siempre que cuando a sea 2 o 3, el R6 pueda ser igual o diferente; y siempre que cuando b sea 2 o 3, R7 pueda ser el mismo o diferente; y cuando Q es un enlace, R1 también se puede seleccionar de -M-Yd-(CR10R11)-Zh, -Xm-(CR12R13)s-Yn-(CR10R11)t-Zp- o -Xj-(CR10R11)v-Yk-S(O)0-2-; en la que M es -O-, -S-, -S(O)- o -S(O)2-; X, Y y Z se seleccionan de manera independiente del grupo que se encuentra conformado por -CH2-, -CH(alquilo C1-6)- y -C(di-alquilo(C1-6)); R10 y R12 se seleccionan de manera independiente del grupo que se encuentra conformado por -OR14, -O(CO)R14, -O(CO)OR15 y -O(CO)NR14R15; R11 y R13 se seleccionan de manera independiente del grupo que se encuentra conformado por hidrogeno, alquilo (C1-6) y arilo; o R10 y R11 juntos son =O, o R12 y R13 juntos son =O; d es 1, 2 o 3; h es 0, 1, 2, 3 o 4; s es 0 o 1; t es 0 o 1; m, n y p son de manera independiente 0-4; siempre que al menos uno de s y t sea 1; y la suma de m, n, p, s y t es 1-6; siempre que cuando p sea 0 y t sea 1, la suma de m, s y n sea 1-5; y siempre que cuando p sea 0 y s sea 1, la suma de m, t y n sea 1-5; v es 0 o 1; j y k son de manera independiente 1-5, siempre que la suma de j, k y v sea 1-5; R2 es sustituyentes 1-3 en los átomos de carbono de anillo que se seleccionan del grupo que se encuentra conformado por hidrogeno, alquilo C1-10, alquenilo C2-10, alquinilo C2-10, cicloalquilo C3-6, cicloalquenilo C3-6, arilo R17-sustituido, bencilo R17-sustituido, benciloxi R17-sustituido, ariloxi R17-sustituido, halogeno, -NR14R15, NR14R15(alquileno C1-6)-, NR14R15C(O)(alquileno C1-6)-, -NHC(CO)R16, OH, alcoxi C1-6, -OC(O)R16, -COR14, hidroxi-alquilo C1-6, alcoxi C1-6alquilo C1-6, NO2, S(O)0-2R16, -SO2NR14R15 y -(alquileno C1-6)COOR14 cuando R2 es un sustituyente en un anillo heterocicloalquilo, R2 es de acuerdo con lo que se define, o es =O o un resto de formula (4); y, en el que R2 es un sustituyente en un nitrogeno de anillo sustituible, es hidrogeno, alquilo C1-6, arilo, alcoxi C1-6, ariloxi, alquilcarbonilo C1-6, arilcarbonilo, hidroxi, -(CH2)1-6CONR18R18, o un resto del grupo de formulas (5); en la que J es -O-, -NH-, -NR18- o -CH2; R3 y R4 se seleccionan de manera independiente del grupo que se encuentra conformado por sustituyentes 1-3 que se seleccionan de manera independiente del grupo que se encuentra conformado por alquilo C1-6, -OR14, -O(CO)R14, -O(CO)OR16, -O(CH2)1-5OR14, -O(CO)NR14R15, -NR14R15, -NR14(CO)R15-NR14(CO)OR16, -NR14(CO)NR15R19, -NR14SO2R16, -COOR14, -CONR14R15, -COR14, -SO2NR14R15, S(O)0-2R16, -O(CH2)1-10-COOR14, -O(CH2)1-10CONR14R15, -(alquileno C1-6)-COOR14, -CH=CH-COOR14, -CF3, -CN, -NO2 y halogeno; R8 es hidrogeno, alquilo C1-6, arilo alquilo C1-6, -C(O)R14 o COOR14; R9 y R17 son de manera independiente grupos 1-3 que se seleccionan de manera independiente del grupo que se encuentra conformado por hidrogeno, alquilo C1-6, alcoxi C1-6, COOH, NO2, NR14R15, OH y halogeno; R14 y R15 se seleccionan de manera independiente del grupo que se encuentra conformado por hidrogeno, alquilo C1-6, arilo y alquilo C1-6 de arilo-sustituido; R16 es alquilo C1-6, arilo, o arilo R17-sustituido; R18 es hidrogeno o alquilo C1-6; y R19 es hidrogeno, hidroxi o alcoxi C1-6; (c) formula (6) o sus isomeros, o sales o solvatos que son aceptables para uso farmacéutico de los compuestos de la formula (6) o de sus isomeros, o prodrogas de los compuestos de la formula (6) o de sus isomeros, sales o solvatos en los que, en la formula (6) anterior: Ar1 es arilo, arilo R10-sustituido o heteroarilo; Ar2 es arilo o arilo R4-sustituido; Ar3 es arilo o arilo R5-sustituido; X e Y se seleccionan de manera independiente del grupo que se encuentra conformado por -CH2-, -CH(alquilo inferior)- y -C-(dialquilo inferior)-; R es -OR6, -O(O)R6, o -O(CO)OR9 o -O(CO)NR6R7; R1 es hidrogeno, alquilo inferior o arilo; o R y R1 juntos son =O; q es 0 o 1; r es = 0, 1 o 2; m y n son de manera independiente 0, 1, 2, 3, o 5; siempre que la suma de m, n y q sea 1, 2, 3, 4, o 5; R4 es sustituyentes 1-5 que se seleccionan de manera independiente del grupo que se encuentra conformado por alquilo inferior, -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, O(CH2)1-1OCONR6R7, -(alquileno inferior)COOR6, -CH=CH-COOR6; R5 es sustituyentes 1-5 que se seleccionan de manera independiente del grupo que se encuentra conformado por -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -CF3, -CN, -NO2, halogeno, -(alquileno inferior)COOR6 y -CH=CH-COOR6; R6, R7 y R8 se seleccionan de manera independiente del grupo que se encuentra conformado por hidrogeno, alquilo inferior, arilo, y alquilo inferior de arilo sustituido; y R9 es alquilo inferior, arilo o alquilo inferior de arilo sustituido. R10 es sustituyentes 1-5 que se seleccionan de manera independiente del grupo que se encuentra conformado por alquilo inferior, -OR6, -O(CO)R6, -O(CO)OR9, -O(CH2)1-5OR6, -O(CO)NR6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, .-NR6(CO)NR7R8, -NR6SO2R9, -COOR6, -CONR6R7, -COR6, -SO2NR6R7, -S(O)0-2R9, -O(CH2)1-10-COOR6, -O(CH2)1-10CONR6R7, -CF3, -CN, -NO2 y halogeno; (d) formula (7) o isomeros de los compuestos de la formula (7), o sales o solvatos que son aceptables para uso farmacéutico de los compuestos de la formula (7) o de los isomeros de los compuestos de la formula (7), o prodrogas de los compuestos de la formula (7) o de los isomeros, sales o solvatos de los compuestos de la formula (7), en los que: R1 es >CH-, >C(alquilo inferior)-, >CF-, >C(OH)-. >C(C6H5)-, >C(C6H4-R15)-, >N- o s+NO--; R2 y R3 se seleccionan de manera independiente del grupo que se encuentra conformado por: -CH2-, -CH(alquilo inferior)-, -C(dialquilo inferior)-, -CH=CH- y -C(alquilo inferior)=CH-; o R1 junto con un R2 adyacente, o R1 junto con un R3 adyacente, forman un grupo -CH=CH- o uno -CH=C(alquilo inferior)-; u y v son de manera independiente 0, 1, 2, o 3, siempre que ambos no sean cero;
ARP080100736A 2001-01-26 2008-02-22 Composiciones y combinaciones terapeuticas deinhibidor (es) de absorcion de esterol con agente (s) cardiovascular (es) y el uso de las mismas para la preparacion de medicamentos para el tratamiento de afecciones vasculares AR066143A2 (es)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US26460001P 2001-01-26 2001-01-26
US26427501P 2001-01-26 2001-01-26
US26439601P 2001-01-26 2001-01-26
US32384201P 2001-09-21 2001-09-21

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AR066143A2 true AR066143A2 (es) 2009-07-29

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ARP020100270A AR032643A1 (es) 2001-01-26 2002-01-25 Combinaciones de inhibidor(es) de absorcion de esterol con agente(s) cardiovascular(es) para el tratamiento de condiciones vasculares
ARP080100736A AR066143A2 (es) 2001-01-26 2008-02-22 Composiciones y combinaciones terapeuticas deinhibidor (es) de absorcion de esterol con agente (s) cardiovascular (es) y el uso de las mismas para la preparacion de medicamentos para el tratamiento de afecciones vasculares

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EP1385548B1 (en) 2007-05-23
KR20080077033A (ko) 2008-08-20
NO20033358L (no) 2003-09-12
EP1541175A3 (en) 2006-04-12
HK1060854A1 (en) 2004-08-27
CY1106791T1 (el) 2012-05-23
SI1385548T1 (sl) 2007-10-31
DE60220269T2 (de) 2008-01-17
RU2003126186A (ru) 2005-03-10
ES2286233T3 (es) 2007-12-01
MXPA03006724A (es) 2003-10-24
WO2002058731A3 (en) 2003-11-20
EP1541175A2 (en) 2005-06-15
AU2002241903B2 (en) 2005-11-24
WO2002058731A2 (en) 2002-08-01
NO20033358D0 (no) 2003-07-25
JP2004517919A (ja) 2004-06-17
HUP0303923A2 (hu) 2004-03-01
IL190173A0 (en) 2008-08-07
ATE362757T1 (de) 2007-06-15
CA2434436A1 (en) 2002-08-01
SK9492003A3 (en) 2003-12-02
AR032643A1 (es) 2003-11-19
DE60220269D1 (de) 2007-07-05
KR20040025889A (ko) 2004-03-26
NZ545332A (en) 2007-09-28
EP1385548A2 (en) 2004-02-04
EP2039357A2 (en) 2009-03-25
DK1385548T3 (da) 2007-09-10
US20030069221A1 (en) 2003-04-10
PT1385548E (pt) 2007-08-24
BR0206644A (pt) 2004-02-25
IL156585A0 (en) 2004-01-04
PL369033A1 (en) 2005-04-18
CZ20032031A3 (cs) 2003-12-17
ECSP074704A (es) 2008-01-23

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