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AR039563A1 - Derivados de 4-(imidazol-5-il)-2-(4-sulfoanilino)pirimidina con actividad inhibidora de cdk - Google Patents

Derivados de 4-(imidazol-5-il)-2-(4-sulfoanilino)pirimidina con actividad inhibidora de cdk

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Publication number
AR039563A1
AR039563A1 ARP030100799A ARP030100799A AR039563A1 AR 039563 A1 AR039563 A1 AR 039563A1 AR P030100799 A ARP030100799 A AR P030100799A AR P030100799 A ARP030100799 A AR P030100799A AR 039563 A1 AR039563 A1 AR 039563A1
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Argentina
Prior art keywords
alkyl
ethyl
heterocyclyl
hydrogen
optionally substituted
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ARP030100799A
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English (en)
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Ab Astrazeneca
Andrew Thomas
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Ab Astrazeneca
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Publication of AR039563A1 publication Critical patent/AR039563A1/es

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Abstract

Derivados de 4-(imidazol-5-il)-2-(4-sulfoanilino)pirimidina y su uso como medicamentos, particularmente medicamentos para producir un efecto inhibidor del ciclo celular (anti-proliferación celular) en un animal de sangre caliente, por ejemplo un ser humano. Reivindicación 1: Un compuesto de la fórmula (2), (3), (4), (5), (6) y (7) de la estructura genérica de fórmula (1), donde: i) un compuesto de fórmula (2), donde: R1 es 2-(pirazolil-1-il)etilo, 3-(isoxazol-3-iloxi)propilo, 2-(isotiazol-3-iloxi)etilo, 2-(tiadiazol-3-iloxi)etilo, 1,3-dihidroxiprop-2-ilo, 1-metil-1-hidroximetiletilo, 1,1-dimetilpropilo, 1-metilciclopropilo, t-butilo, 2-morfolino-1,1-dimetiletilo, 2-pirrolidin-1-il-1,1-dimetiletilo, 2-metiltio-1,1-dimetiletilo, 1,3-dimetoxiprop-2-ilo, 1-metoxiprop-2-ilo, 1-hidroxiprop-2-ilo, 1-etoxiprop-2-ilo, 1-propoxiprop-2-ilo, etoxietilo o 2-metoxi-1,1-dimetiletilo; y R2 es hidrógeno; o R1 y R2 juntos forman 2,2-dimetilaziridin-1-ilo; o una sal aceptable para uso farmacéutico o un éster hidrolizable in vivo del mismo; ii) un compuesto de fórmula (3) donde: R1 es pirid-2-ilmetilo, 2-(2-metil-1,2,4-triazol-5-il)etilo, 2-pirid-2-iletilo, 2-piridazin-3-iletilo, 2-(3,5-dimetiltriazol-4-il)etilo, 2-pirid-3-iletilo, 2-metoxietilo, 3-(5-metilpirazol-4-il)propilo, 2-trifluorometilpirid-5-ilmetilo, 2-piridazin-4-iletilo, 1,1-dimetilprop-2-inilo, 2-etoxietilo, 2-fenoxietilo, 2-(4-metoxifenoxi)etilo, 2-(2-metoxifenoxi)etilo, 2-(viniloxi)etilo, 2-(isopropoxi)etilo y 2-(propoxi)etilo; y R2 es hidrógeno o ciano; o una sal aceptable para uso farmacéutico o un éster hidrolizable in vivo del mismo; con la salvedad de que cuando R1 es 2-metoxietilo, R2 es ciano; iii) un compuesto de fórmula (4), donde: R1 es hidrógeno, heterociclilo, alquilo C1-6 o alcoxi C1-6alquilo C1-6; donde R1 puede ser opcionalmente substituido sobre carbono por uno o más hidroxi, carboxi, alcoxi C1-6, alcoxicarbonilo C1-6, N,N-(alquil C1-6)2amino, heterociclilo, cicloalquilo C3-6 y alcoxi C1-6alcoxi C1-6; y donde si un heterociclilo contiene una porción -NH-, ese nitrógeno puede ser opcionalmente substituido por alquilo C1-6 o bencilo; R2 es hidrógeno, halo o ciano; o una sal aceptable para uso farmacéutico o un éster hidrolizable in vivo del mismo ; con la salvedad de que cuando R1 es 2-metoxietilo, ciclopropilmetilo o pirid-2-ilmetilo, R2 no es hidrógeno; iv) un compuesto de fórmula (5), donde: R1 es hidrógeno, alquilo C1-4, alquenilo C2-4, alquinilo C2-4, cicloalquilo C3-6, cicloalquil C3-6alquilo C1-3, un heterociclilo o heterociclilalquilo C1-3; donde R1 puede ser opcionalmente substituido sobre carbono por uno o más metilo, etilo, metoxi, etoxi, propoxi, trifluorometilo, trifluorometoxi, 2,2,2-trifluoroetoxi o ciclopropilmetoxi; y donde si dicho heterociclilo contiene una porción -NH- ese nitrógeno puede ser opcionalmente substituido por uno o más metilo, etilo, acetilo, 2,2,2-trifluoroetilo o metoxietilo; R2 es hidrógeno, halo o ciano; R3 es alquilo C2-6; o una sal aceptable para uso farmacéutico o un éster hidrolizable in vivo del mismo; v) un compuesto de fórmula (6), donde: R1 es hidrógeno, alquilo C1-4, alquenilo C2-4, alquinilo C2-4, cicloalquilo C3-6, cicloalquil C3-6-alquilo C1-3, un heterociclilo o heterociclilalquilo C1-3; donde R1 puede ser opcionalmente substituido sobre carbono por uno o más metilo, etilo, metoxi, etoxi, propoxi, trifluorometilo, trifluorometoxi, 2,2,2-trifluoroetoxi o ciclopropilmetoxi; y donde si dicho heterociclilo contiene una porción -NH- ese nitrógeno puede ser opcionalmente substituido por uno o más metilo, etilo, acetilo, 2,2,2-trifluoroetilo o metoxietilo; R2 es halo, ciano, alquilo C1-3 o alcoxi C1-3; p es 1-2; donde los valores de R2 pueden ser iguales o diferentes; R3 es hidrógeno, halo o ciano; R4 es alquilo C1-4; R5 es alquilo C1-6 o alquenilo C2-6; donde R5 puede ser opcionalmente substituido sobre carbono por uno o más metoxi, etoxi, propoxi, trifluorometilo, trifluorometoxi, 2,2, 2-trifluoroetoxi o ciclopropilmetoxi; o una sal aceptable para uso farmacéutico o un éster hidrolizable in vivo del mismo; con la salvedad que dicho compuesto no es 4-(1,2-dimetilimidazol-5-il)-2-[2-metoxi-4-(N-metilsulfamoil)-5-metilanilino]pirimidina; vi) un compuesto de fórmula (7), donde: R1 es alquilo C1-4, alquenilo C2-4, alquinilo C2-4, cicloalquilo C3-6, cicloalquil C3-6alquilo C1-3, un heterociclilo o heterociclilalquilo C1-3; donde R1 puede ser opcionalmente substituido sobre carbono por uno o más metilo, etilo, metoxi, etoxi, propoxi, trifluorometilo, trifluorometoxi, dimetilamino, 2,2,2-trifluoroetoxi, fenil o ciclopropilmetoxi; y donde si dicho heterociclilo contiene una porción -NH- es nitrógeno puede ser opcionalmente substituido por uno o más metilo, etilo, acetilo, 2,2,2-trifluoroetilo o metoxietilo; R2 es halo, ciano, alquilo C1-3 o alcoxi C1-3; p es 0-2; donde los valores de R2 pueden ser iguales o diferentes; R3 es hidrógeno, halo o ciano; R4 es alquilo C2-6; R5 es alquilo C1-6 o alquenilo C2-6; donde R5 puede ser opcionalmente substituido sobre carbono por uno o más metoxi, etoxi, propoxi, trifluorometil, trifluorometoxi, 2,2,2-trifluoroetoxi o ciclopropilmetoxi; o una sal aceptable para uso farmacéutico o un éster hidrolizable in vivo del mismo; vii) un compuesto de fórmula (8), donde: R1 es alquilo C1-4, alquenilo C2-4, alquinilo C2-4, cicloalquilo C3-6, cicloalquil C3-6alquilo C1-3, un heterociclilo o heterociclilalquilo C1-3; donde R1 puede ser opcionalmente substituido sobre carbono por uno o más metilo, etilo, metoxi, etoxi, propoxi, trifluorometilo, trifluorometoxi, dimetilamino, 2,2,2-trifluoroetoxi, fenilo o ciclopropilmetoxi; y donde si dicho heterociclilo contiene una porción -NH- ese nitrógeno puede ser opcionalmente substituido por uno o más metilo, etilo, acetilo, 2,2,2-trifluoroetilo o metoxietilo; R2 es halo, ciano, alquilo C1-3 o alcoxi C1-3; p es 0-2; donde los valores de R2 pueden ser iguales o diferentes; R3 es hidrógeno, halo o ciano; R4 es n-propilo o alquilo C4-6; o una sal aceptable para uso farmacéutico o un éster hidrolizable in vivo del mismo.
ARP030100799A 2002-03-09 2003-03-07 Derivados de 4-(imidazol-5-il)-2-(4-sulfoanilino)pirimidina con actividad inhibidora de cdk AR039563A1 (es)

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JP2005524672A (ja) 2002-03-09 2005-08-18 アストラゼネカ アクチボラグ Ｃｄｋ阻害活性を有するイミダゾリル置換ピリミジン誘導体
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