AR066505A1 - Derivados de fenilaminobenceno sustituidos de utilidad para el tratamiento de trastornos y enfermedades hiperproliferativos asociados con actividad quinasa extracelular mediada por mitogenos - Google Patents

Derivados de fenilaminobenceno sustituidos de utilidad para el tratamiento de trastornos y enfermedades hiperproliferativos asociados con actividad quinasa extracelular mediada por mitogenos

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Publication number
AR066505A1
AR066505A1 ARP080101967A ARP080101967A AR066505A1 AR 066505 A1 AR066505 A1 AR 066505A1 AR P080101967 A ARP080101967 A AR P080101967A AR P080101967 A ARP080101967 A AR P080101967A AR 066505 A1 AR066505 A1 AR 066505A1
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AR
Argentina
Prior art keywords
alkyl
group
independently
cycloalkyl
aryl
Prior art date
Application number
ARP080101967A
Other languages
English (en)
Inventor
Yingfu Li
Marian Rudolf
Mario Lobell
Daniel Auclair
Jacques Dumas
Original Assignee
Bayer Schering Pharma Ag
Bayer Healthcare Ag
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Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=39666034&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR066505(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Schering Pharma Ag, Bayer Healthcare Ag filed Critical Bayer Schering Pharma Ag
Publication of AR066505A1 publication Critical patent/AR066505A1/es

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Abstract

Composiciones farmacéuticas que contienen dichos compuestos y el uso de tales compuestos o composiciones para el tratamiento de trastornos hiperproliferativos y/o de angiogénesis, como un agente unico o en combinacion con otros ingredientes activos. Reivindicacion 1: Un compuesto caracterizado porque responde a la formula general (1) en donde R1 y R2 son iguales o diferentes y son en forma independiente un átomo de hidrogeno, un átomo de halogeno, un grupo alquilo C1-6, alquenilo C2-6,alquinilo C2-6, o -CN, en donde al menos uno de R1 y R2 es un átomo de halogeno; cada instancia de R3 es en forma independiente un átomo de halogeno, un grupo alquilo C1-4 o -CN; q es un entero entre 0, 1, 2, o 3; R4 es un átomo de hidrogeno o ungrupo alquilo C1-6; R5 es un grupo -C(=O)R7, -C(=O)OR7, -C(=O)N(R7)(R8), NHC(=O)R7, -S(=O)2R7, -NHS(=O)2R7, -S(=O)2NR7R8, -NO2, -CN, o un grupo de formula (2) en donde cada uno de Z1, Z2, Z3 y Z4 es en forma independiente -CH-, -C(alquil C1-6)-, -C(=O)-, -S-, -O-, -N- o -NH, de manera que al menos uno de Z1, Z2, Z3 y Z4 es -N- o -NH-; X es -O-, -NH-, -N(C1-6 alquil)-, -S-, -S(=O)2-, -C(=O)-, -C(=O)O-, -C(=O)NH, o -NHC(=O)-; R6 es -(CH2)n-(CH(OR11))-(CH2)m-R9, -(CR152)n-(CR15(OR11))-CR152)m-R9, -(CH2)n-(CHN((R12)(R13)))-(CH2)mR10, -(CR152)n-(CR15N(R12)(R13)))-(CR152)m-R10, -(CH2)n-Y, -(CH2)n-CH(OH)-CH(OH)-CH2(OH), o -(CH2)nCH(OH)-C(=O)OH; Y es un grupo -S(=O)2NH2 -S(=O)2NH(alquilo C1-3), -N(R12)(R13), arilo, heteroarilo, alquenilo C2-10, cicloalquenilo C5-10, cicloalquilo o heterocicloalquilo, en donde arilo, heteroarilo, cicloalquilo, o heterocicloalquilo está opcionalmente sustituido con uno o más grupos -(CH2)oR14; R7 y R8 son en forma independiente un átono de hidrogeno, ungrupo -N(R12)(R13), -OH, alcoxi C1-6, alquilo C1-6, -CF3, -O(CH2)n-(CH(OR11))-(CH2)m-R9, -O-(CH2)n-cicloalquilo, arilo, heteroarilo, cicloalquilo o heterocicloalquilo, en donde arilo, heteroarilo, cicloalquilo, o heterocicloalquilo estánopcionalmente sustituidos en forma independiente entre sí con uno o más átomos de halogeno, grupos alquilo C1-6 o alcoxi C1-6; R9 y R10 son en forma independiente -OH, alcoxi C1-6, halogeno, heteroarilo, -NRd1Rd2 o -N(R12)(R13); R11, R12 y R13 sonen forma independiente un átomo de hidrogeno, un grupo alquilo C1-6, arilo, heteroarilo, cicloalquil o heterocicloalquilo, en donde alquilo C1-6, arilo, heteroarilo, cicloalquilo, o heterocicloalquilo están opcionalmente sustituidos en formaindependiente entre sí con uno o más grupos o -(CH2)oR14, o R12 y R13, junto con el átomo de N al cual están unidos, forman un anillo heterocíclico de 5, 6 o 7 miembros que comprende opcionalmente uno o más heteroátomos adicionales, que comprendeopcionalmente uno o más grupos -C(=O)- o -S(=O)2, y que está opcionalmente sustituido con uno o más grupos -(CH2)oR14; cada instancia de R14 es, en forma independiente, un átomo de halogeno, un grupo alquilo C1-6, haloalquilo C1-6, alcoxialquilo C1-6, cicloalquilo, heterocicloalquilo, -ORc, -NRd1Rd2, -CN, -NHS(=O)2H, -NRaS(=O)2Rb, -S(=O)2Rb o -C(=O)Rb; cada instancia de R15 es, en forma independiente, un átomo de hidrogeno o un grupo alquilo C1-6; cada instancia de n es, en formaindependiente, un entero entre 0, 1, 2, 3, o 4; cada instancia de m es, en forma independiente, un entero entre 0, 1, o 2; y cada instancia de o es, en forma independiente, un entero entre 0, 1, o 2; cada instancia de Ra es, en forma independiente,un átomo de hidrogeno o un grupo alquilo C1-6; cada instancia de Rb es, en forma independiente, un grupo -OH, -ORc, -SRc, NRd1Rd2, alquilo C1-6, arilo, heteroarilo, cicloalquilo o heterocicloalquilo, en donde alquilo C1-6, cicloalquilo yheterocicloalquilo están opcionalmente sustituidos en forma independiente entre sí una o más veces con un átomo de halogeno, un grupo -OH o alcoxi C1-6; cada instancia de Rc es, en forma independiente, un átomo de hidrogeno, un grupo -C(=O)Re, -S(=O)2Re, alquilo C1-6, haloalquilo C1-6 cicloalquilo, heterocicloalquilo, arilo, o heteroarilo, en donde alquilo C1-6, haloalquilo C1-6, cicloalquilo, heterocicloalquilo, arilo, o heteroarilo, están opcionalmente sustituidos en forma independienteentre sí una o más veces con un átomo de halogeno, un grupo -OH, arilo, -ORf, -NRd1Rd2, o -OP(=O)(ORf)2; en cada instancia de Rd1, Rd2, Rd1, Rd2 son, en forma independiente entre sí, un átomo de hidrogeno, un grupo alquilo C1-6, cicloalquilo,heterocicloalquilo, arilo, heteroarilo, -C(=O)Re, -S(=O)2Re, o -C(=O)NRg1Rg2, en donde alquilo C1-6, cicloalquilo, heterocicloalquilo, arilo, o heteroarilo están opcionalmente sustituidos en forma independiente entre sí una o más veces, en la mismaforma o en forma diferente, con un átomo de halogeno, un grupo -OH o arilo, -NRg1Rg2, -ORf, -C(=O)Re, -S(=O)2Re, o -OP(=O)(ORf)2; o Rd1 y Rd2, junto con el átomo de nitrogeno al cual están unidos, forman un anillo heterocicloalquilo de 3, 4, 5, 6,7, 8, 9 o 10 miembros, que está opcionalmente sustituido una o más veces, en la misma forma o en forma diferente, con un átomo de halogeno, un grupo alquilo C1-6, -NRg1Rg2, -ORf, -C(=O)Re, -S(=O)2Re, o -OP(=O)(ORf)2; y la estructura de carbono de lamisma está opcionalmente interrumpida una o más veces, en la misma forma o en forma diferente, con NH, NRd3, O, o S, y está opcionalmente interrumpida una o más veces, en la misma forma o en forma diferente, con un grupo -C(=O)-, -S(=O)-, y/o -S(=O)2-, y opcionalmente contiene uno o más enlaces dobles; Rd3 es un átomo de hidrogeno, un grupo alquilo C1-6, cicloalquilo, heterocicloalquilo, arilo, o heteroarilo, en donde alquilo C1-6 o cicloalquilo están opcionalmente sustituidos en formaindependiente entre sí una o más veces con un átomo de halogeno, un grupo -OH, alquilo C1-6, cicloalquilo, haloalquilo C1-6 o alcoxi C1-6; Re es un grupo -NRg1Rg2, alquilo C1-6, cicloalquilo, alcoxi C1-6, arilo o heteroarilo; Rf es un átomo dehidrogeno, un grupo -C(=O)Re, alquilo C1-6, haloalquilo C1-6, cicloalquilo, heterocicloalquilo, arilo, o heteroarilo, en donde alquilo C1-6, haloalquilo C1-6, cicloalquilo, heterocicloalquilo, arilo, o heteroarilo están opcionalmente sustituidos enforma independiente entre sí una o más veces con un átomo de halogeno, un grupo -OH, alcoxi C1-6, arilo, o -NRg1Rg2; Rg1, Rg2, son, en forma independiente entre sí, un átomo de hidrogeno, un grupo alquilo C1-6, cicloalquilo, heterocicloalquilo,arilo, o heteroarilo; o Rg1 y Rg2, junto con el átomo de nitrogeno al cual están unidos, forman un anillo heterocicloalquilo de 3, 4, 5, 6, 7, 8, 9 o 10 miembros, que está opcionalmente sustituido una o más veces, en la misma forma o en formadiferente, con un átomo de halogeno, un grupo -OH, alquilo C1-6, alcoxi C1-6; y la estructura de carbono de la misma está opcionalmente interrumpida una o más veces, en la misma forma o en forma diferente, con NH, NRa, O, S, y está opcionalmenteinterrumpida una o más veces, en la misma forma o en forma diferente, con un grupo -C(=O)-, -S(=O)-, y/o -S(=O)2-, y opcionalmente contiene uno o más enlaces dobles; con la condicion de que X-R6 no es (O o NH)-(CH2)rRr, donde Rr es NRs1Rs2 en donder =1-4, y Rs1, Rs2 = en forma independiente hidrogeno, alquilo C1-8, o tomados junto con el nitrogeno al cual están unidos, forman un anillo cíclico de entre 3 y 10 miembros que contiene opcionalmente un átomo de oxígeno o un átomo de azufre o ungrupo NH o N-alquilo C1-8; o un tautomero, estereoisomero, sal aceptable para uso fisiologico, hidrato, solvato, metabolito o prodroga del mismo.
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