AR092129A1 - 2,3-benzodiazepinas como inhibidoras de proteinas bet - Google Patents

2,3-benzodiazepinas como inhibidoras de proteinas bet

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Publication number
AR092129A1
AR092129A1 ARP130102888A ARP130102888A AR092129A1 AR 092129 A1 AR092129 A1 AR 092129A1 AR P130102888 A ARP130102888 A AR P130102888A AR P130102888 A ARP130102888 A AR P130102888A AR 092129 A1 AR092129 A1 AR 092129A1
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Argentina
Prior art keywords
alkyl
alkoxy
amino
halo
hydroxy
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ARP130102888A
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English (en)
Inventor
Dr Burle Stefan
Dr Siegel Stephan
Dr Haendler Bernard
Ernesto Dr Fernandez-Montalvan Amaury
Dr Mnning Ursula
Dr Krause Sabine
Dr Lejeune Pascale
Dr Schmees Norbert
Dr Busemann Matthias
Dr Holton Simon
Dr Cleve Arwed
Kuhnke Joachim
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Bayer Pharma Aktiengellschaft
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=48979774&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR092129(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Pharma Aktiengellschaft filed Critical Bayer Pharma Aktiengellschaft
Publication of AR092129A1 publication Critical patent/AR092129A1/es

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Abstract

Se describen 2,3-benzodiazepinas inhibidores de proteínas BET, especialmente inhibidoras de BRD4, productos intermedios para la preparación de los compuestos según la presente, agentes farmacéuticos que contienen los compuestos, así como su uso profiláctico y terapéutico en enfermedades hiperproliferativas, especialmente en enfermedades tumorales. Además, se describe el uso de inhibidores de proteínas BET en hiperplasias benignas, enfermedades ateroscleróticas, septicemia, enfermedades autoinmunitarias, enfermedades vasculares, infecciones virales, en enfermedades neurodegenerativas, en enfermedades inflamatorias, en enfermedades ateroscleróticas y en el control de la fertilidad masculina. Reivindicación 1: Compuestos de fórmula general (1) en la que X representa un átomo de oxígeno o de azufre, y A representa un anillo de heteroarilo monocíclico con 5 ó 6 átomos de anillo o representa un anillo de fenilo, y R¹ᵃ representa hidrógeno, halógeno, ciano, carboxi, amino o aminosulfonilo, o representa un resto alcoxi C₁₋₆, alcoxi C₁₋₃-alquilo C₁₋₃, alcoxi C₁₋₃-alcoxi C₂₋₃, alquil C₁₋₆-amino, alquil C₁₋₆-carbonilamino, alquil C₁₋₆-amino-alquilo C₁₋₆, N-(heterociclil)-alquilo C₁₋₆, N-(heterociclil)-alcoxi C₁₋₆, hidroxi-alquilo C₁₋₆, hidroxi-alcoxi C₁₋₆, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆, alquil C₁₋₆-carbonilo o alcoxi C₁₋₆-carbonilo, o representa un resto heterociclilo monocíclico con 3 a 8 átomos de anillo que dado el caso puede estar sustituido una o varias veces, de manera igual o diferente, con halógeno, ciano, nitro, hidroxi, amino, oxo, carboxi, alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, hidroxialquilo C₁₋₆, alquil C₁₋₆-amino, amino-alquilo C₁₋₆, alquil C₁₋₆-amino-alquilo C₁₋₆, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆, cicloalquilo C₃₋₁₀, fenilo, halofenilo, fenil-alquilo C₁₋₆, piridinilo, -NR⁶C(=O)-R⁹, -C(=O)-NR⁶R⁷, -C(=O)-R⁸, -S(=O)₂-NR⁶R⁷, -S(=O)-R⁹, -S(=O)₂-R⁹, -NH-S(=O)₂-R⁹ y/o un resto heterociclilo monocíclico con 3 a 8 átomos de anillo, o representa un resto heteroarilo monocíclico con 5 ó 6 átomos de anillo que dado el caso puede estar sustituido una o varias veces, de manera igual o diferente, con halógeno, hidroxi, amino, ciano, nitro, carboxi, alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, alquil C₁₋₆-amino, amino-alquilo C₁₋₆, alquil C₁₋₆-amino-alquilo C₁₋₆, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆, cicloalquilo C₃₋₁₀, -C(=O)-NR⁶R⁷, -C(=O)-R⁸, -S(=O)₂-NR⁶R⁷, -S(=O)-R⁹, -S(=O)₂-R⁹, -NH-S(=O)₂-R⁹ y/o con un resto heterociclilo monocíclico con 3 a 8 átomos de anillo, y/o con un resto heteroarilo monocíclico con 5 ó 6 átomos de anillo, y/o con un resto fenilo, que a su vez puede estar sustituido dado el caso una o varias veces, de manera igual o diferente, con halógeno, alquilo C₁₋₃ y/o alcoxi C₁₋₃, o representa un resto fenilo que dado el caso puede estar sustituido una o varias veces, de manera igual o diferente, con halógeno, amino, hidroxi, ciano, nitro, carboxi, alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, alquil C₁₋₆-amino, amino-alquilo C₁₋₆, alquil C₁₋₆-amino-alquilo C₁₋₆, -C(=O)NR⁶R⁷, -C(=O)R⁸, alquil C₁₋₃-sulfinilo, alquil C₁₋₃-sulfonilo, -S(=O)₂NH₂, alquil C₁₋₃-sulfonilamino, alquil C₁₋₃-aminosulfonilo, cicloalquil C₃₋₆-aminosulfonilo, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆, hidroxi alquil C₁₋₆, cicloalquilo C₃₋₁₀ y/o un resto heterociclilo monocíclico con 3 a 8 átomos de anillo y/o un resto heteroarilo monocíclico con 5 ó 6 átomos de anillo, que a su vez dado el caso puede estar sustituido una o varias veces, de manera igual o diferente, con halógeno, alquilo C₁₋₃ y/o alcoxi C₁₋₃, y R¹ᵇ y R¹ᶜ representan, independientemente entre sí, hidrógeno, halógeno, hidroxi, ciano, nitro y/o representa un resto alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆, cicloalquilo C₃₋₁₀ y/o un resto heterociclilo monocíclico con 3 a 8 átomos de anillo, y R² representa un resto alquilo C₁₋₃ o trifluorometilo o cicloalquilo C₃ o C₄, y R³ representa ciclopropilo, alquilo C₁₋₃, alcoxi C₁₋₃, amino, ciclopropilamino o alquil C₁₋₃-amino, y R⁴ y R⁵ representan, independientemente entre sí, hidrógeno, hidroxi, ciano, nitro, amino, aminocarbonilo, flúor, cloro, bromo, alquilo C₁₋₆, alcoxi C₁₋₆, alquil C₁₋₆-amino, alquil C₁₋₆-carbonilamino, alquil C₁₋₆-aminocarbonilo o alquil C₁₋₆-aminosulfonilo, o representan alquilo C₁₋₆, alcoxi C₁₋₆, alquil C₁₋₆-amino, alquil C₁₋₆-carbonilamino, alquil C₁₋₆-aminocarbonilo o alquil C₁₋₆-aminosulfonilo que dado el caso pueden estar sustituidos una o varias veces, de manera igual o diferente, con halógeno, amino, hidroxi, carboxi, hidroxi-alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, alquil C₁₋₆-amino, amino-alquilo C₁₋₆, heterociclilo monocíclico con 3 a 8 átomos de anillo y/o heteroarilo monocíclico con 5 ó 6 átomos de anillo, pudiendo estar los restos heterociclilo y heteroarilo monocíclicos mencionados a su vez dado el caso sustituidos una vez con alquilo C₁₋₃, o representan cicloalquilo C₃₋₁₀ que dado el caso puede estar sustituido una o varias veces, de manera igual o diferente, con halógeno, amino, hidroxi, carboxi, alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, alquil C₁₋₆-amino, amino-alquilo C₁₋₈, alquil C₁₋₆-amino-alquilo C₁₋₆, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆ y/o un resto heterociclilo monocíclico con 3 a 8 átomos de anillo, o representan heteroarilo monocíclico con 5 ó 6 átomos de anillo que dado el caso puede estar sustituido una o varias veces, de manera igual o diferente, con halógeno, amino, hidroxi, ciano, nitro, carboxi, alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, hidroxi-alquilo C₁₋₆, alquil C₁₋₆-amino, amino-alquilo C₁₋₆, alquil C₁₋₆-amino-alquilo C₁₋₆, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆, cicloalquilo C₃₋₁₀, -C(=O)R⁸, -S(=O)₂R⁹, -NR⁶R⁷ y/o un resto heterociclilo monocíclico con 3 a 8 átomos de anillo, o representan heterociclilo monocíclico con 3 a 8 átomos de anillo que dado el caso puede estar sustituido una o varias veces, de manera igual o diferente, con halógeno, amino, hidroxi, ciano, oxo, carboxi, alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, alquil C₁₋₆-amino, amino-alquilo C₁₋₆, alquil C₁₋₆-amino-alquilo C₁₋₆, hidroxi-alquilo C₁₋₆, halo-alquilo C₁₋₆, halo-alcoxi C₁₋₆, cicloalquilo C₃₋₁₀, -C(=O)R⁸, -S(=O)₂R⁹, -NR⁶R⁷ y/o un resto heterociclilo monocíclico con 3 a 8 átomos de anillo, o representan fenilo que dado el caso puede estar sustituido una o varias veces, de manera igual o diferente, con halógeno, amino, hidroxi, ciano, nitro, carboxi, alquilo C₁₋₆, alcoxi C₁₋₆, alcoxi C₁₋₆-alquilo C₁₋₆, alquil C₁₋₆-amino, amino-alquilo C₁₋₆, alquil C₁₋₆-aminocarbonilo, alquil C₁₋₆-aminosulfonilo, alquil C₁₋₆-amino-alquilo C₁₋₆, hidroxi-alquilo C₁₋₆, halo-alquilo C₁₋
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