SMAILL JEFFREY BRUCE,PATTERSON ADAM VORN,LU GUO-LIANG,LEE HO HUAT,ASHOORZADEH AMIR,ANDERSON ROBERT FORBES,WILSON WILLIAM ROBERT,DENNY WILLIAM ALEXANDER,HSU HUAI-LING (ANNIE),MAROZ ANDREJ,JAMIESON STEP
申请号：
ZA201200994
公开号：
ZA201200994B
申请日:
2012.02.10
申请国别(地区):
ZA
年份:
2012
代理人:
摘要：
The invention provides kinase inhibitors of Formula I: wherein either: (1) R1 is H, and (a) R2 is (3-chlorobenzyl)oxy-and R3 is chloro； (b) R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole； (c) R2 is 2-pyridinylmethoxy and R3 is chloro； (d) R2 and R3 are both chloro； (e) R2 is chloro and R1 is bromo； (f) R2 and R3 are both bromo； (g) R2 is fluoro and R3 is ethynyl； (h) R2 is chloro and R3 is ethynyl； (i) R2 is bromo and R3 is ethynyl； (j) other than when R1 is in the 3-position in combination with R3, in the 4-position, R2 is bromo and R3 is fluoro； (k) R2 is 2-pyridinylmethoxy and R3 is fluoro； or (l) R2 is 2-pyridinylmethoxy and R1 is bromo； or (2) at least one of R1, R2 and R3 is selected from benzyloxy, 3-chlorobenzyloxy and 2-pyridinylmethoxy and when at least one of R1, R2 and R3 is not benzyloxy, 3-chlorobenzyloxy or 2-pyridinylmethoxy, each of the others is independently selected from H, halogen, and C2-C4 alkynyl, with the proviso that when one of R1, R2 and R3 is benzyloxy or 2-pyridinylmethoxy, the other two of R1, R2 and R3 are not H； or (3) two of R1, R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole； and the other is selected from H, halogen and C2-C4 alkynyl. Also provided are reductive prodrugs, comprising a kinase inhibitor as defined above and a reductive trigger linked directly or indirectly to a nitrogen of the kinase inhibitor. Further provided are pharmaceutical compositions, comprising the kinase inhibitors or the prodrugs, and the use of such compositions in therapy, in particular for treating cancer.
