SMAILL JEFFREY BRUCE,스메일, 제프리 브루스,PATTERSON ADAM VORN,패터슨, 아담 보른,LU GUO LIANG,루, 구오-리앙,LEE HO HUAT,리, 호 후앗,ASHOORZADEH AMIR,아쇼르자데, 아미르,ANDERSON ROBERT FORBES,앤더슨, 로버트 포브즈,WILSON WILLIAM ROBERT,윌슨, 윌리엄
申请号：
KR1020127008569
公开号：
KR1020120076350A
申请日:
2010.09.02
申请国别(地区):
KR
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.본 발명은 하기 화학식 I의 키나아제 억제제를 제공한다:상기에서, (1) R1은 H 이고, (a) R2는 (3-클로로벤질)옥시- 이며, R3는 클로로이거나； (b) R2 및 R3는, 그들이 부착되는 탄소 원자와 함께 1-(3-플루오로벤질)-1H-피라졸을 형성하거나； (c) R2는 2-피리디닐메톡시이며, R3는 클로로이거나； (d) R2 및 R3는 모두 클로로이거나； (e) R2는 클로로이고, R3는 브로모이거나； (f) R2 및 R3는 모두 브로모이거나； (g) R2는 플루오로이고, R3는 에티닐이거나； (h) R2는 클로로이고, R3는 에티닐이거나；
