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 R3 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 R2 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 R3 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. |