DÉRIVÉS DE 1-(5-TERT-BUTYL-2-ARYL-PYRAZOL-3-YL)-3-[2-FLUORO-4-[(3-OXO-4H-PYRIDO[2, 3-B]PYRAZIN-8-YL)OXY]PHÉNYL]URÉE EN TANT QU'INHIBITEURS DE RAF POUR LE TRAITEMENT D'UN CANCER
INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE);CANCER RESEARCH TECHNOLOGY LIMITED
发明人:
SPRINGER, Caroline Joy,MARAIS, Richard,GIROTTI, Romina,NICULESCU-DUVAZ, Dan,NICULESCU-DUVAZ, Ion,ZAMBON, Alfonso
申请号：
GBGB2014/053490
公开号：
WO2015/075483A1
申请日:
2014.11.25
申请国别(地区):
GB
年份:
2015
代理人:
摘要：
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)- 3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea compounds (referred herein as "TBAP compounds") that, inter alia, inhibit RAF (e.g., BRAF, CRAF, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF, CRAF, etc.)； and to treat disorders including: proliferative disorders； cancer (including, e.g., malignant melanoma, colorectal carcinoma, pancreatic adenocarcinoma)； inflammation； immunological disorders； viral infections； fibrotic disorders； disorders associated with a mutated form of RAF (e.g., BRAF, CRAF, etc.)； disorders ameliorated by the inhibition of RAF (e.g., BRAF, CRAF, etc.)； disorders ameliorated by the inhibition of mutant BRAF； disorders ameliorated by the inhibition of BRAF and CRAF； disorders associated with RAS mutations and/or MAPK pathway activation； disorders ameliorated by the inhibition of SRC, p38, FGFRA, VEGFR-2 (KDR), and/or LCK； etc.La présente invention concerne d'une façon générale le domaine des composés thérapeutiques. Plus spécifiquement, la présente invention concerne certains composés de 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)- 3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phényl]urée (désignés dans la description « composés TBAP ») qui, entre autres, inhibent RAF (par exemple, BRAF, CRAF, etc.). La présente invention concerne également des compositions pharmaceutiques comprenant de tels composés et l'utilisation de tels composés et de telles compositions, à la fois in vitro et in vivo, pour inhiber RAF (par exemple, BRAF, CRAF, etc.) ； et pour traiter des troubles comprenant : des troubles prolifératifs ； un cancer (y compris, par exemple, un mélanome malin, un carcinome colorectal, un adén
