CANCER RESEARCH TECHNOLOGY LIMITED;INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE);ASTEX THERAPEUTICS LIMITED
发明人:
NICULESCU-DUVAZ, DAN,SPRINGER, CAROLINE JOY,GILL, ADRIAN LIAM,TAYLOR, RICHARD DAVID,MARAIS, RICHARD MALCOLM,DIJKSTRA, HARMEN,GAULON, CATHERINE,MENARD, DELPHINE,ROMAN VELA, ESTEBAN
申请号：
CA2584651
公开号：
CA2584651C
申请日:
2005.10.21
申请国别(地区):
CA
年份:
2013
代理人:
摘要：
The present invention pertains to certain imidazo[4,5-b]pyridin-2-one andoxazolo[4,5-b]pyridin-2-one compounds and analogs thereof, which, inter alia,inhibit RAF (e.g., B-RAF) activity, inhibit cell proliferation, treat cancer,etc., and more particularly to compounds of the formula (I): wherein: J isindependently -O- or -NRN1-； RN1, if present, is independently -H or asubstituent； RN2 is independently -H or a substituent； Y is independently -CH=or -N=； Q is independently -(CH2)j-M-(CH2)k- wherein: j is independently 0, 1or 2； k is independently 0, 1, or 2； j+k is 0, 1, or 2； M is independently -O-, -S-, -NH-, -NMe-, or -CH2-； each of RP1, RP2, RP3, and RP4 is independently -H or a substituent； and additionally RP1 and RP2 taken together may be -CH=CH-CH=CH-； L is independently: a linker group formed by a chain of 2, 3, or 4linker moieties； each linker moiety is independently -CH2-,-NRN-, -C(=X)-, or -S(=O)2-； exactly one linker moiety is -NRN-, or: exactly two linker moietiesare -NRN-； exactly one linker moiety is -C(=X)-, and no linker moiety is -S(=O)2-； or: exactly one linker moiety is -S(=O)2-, and no linker moiety is -C(=X)-； no two adjacent linker moieties are -NRN-； X is independently =O or=S； each RN is independently -H or a substituent； A is independently: C6-14carboaryl, C5-14heteroaryl, C3-12carbocyclic, C3-12heterocyclic； and isindependently unsubstituted or substituted； and pharmaceutically acceptablesalts, solvates, amides, esters, ethers, N-oxides, chemically protected forms,and prodrugs thereof. The present invention also pertains to pharmaceuticalcompositions comprising such compounds, and the use of such compounds andcompositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF)activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cellproliferation, and in the treatment of diseases and conditions that areameliorated by the inhibition of RAF, RTK, etc., proliferative c
