| 主权项 |
1. A method of treating cancer comprising administering a therapeutically effective amount of a compound of Formula I: wherein Y2 is O, S, NR6, NCOR6, or NSO2R6 R6 is C1-C6 alkyl, C1-C6 heteroalkyl, aryl, or heteroaryl; R3 and R4 are independently selected from the group consisting of 2-haloalkyl, 2-alkylsulfonyloxyalkyl, 2-heteroalkylsulfonyloxyalkyl, 2-arylsulfonyloxyalkyl, and 2-heteroalkylsulfonyloxyalkyl; R1 has the formula L-Z3; L is C(Z1)2; each Z1 independently is hydrogen, halogen, C1-C6 alkyl, C1-C6 heteroalkyl, aryl, heteroaryl, C3-C8 cycloalkyl, heterocyclyl, C1-C6 acyl, C1-C6 heteroacyl, aroyl, or heteroaroyl; or L is: Z3 is a bioreductive group having a formula selected from the group consisting of: each X1 is independently N or CR8; X2 is NR7, S, or O; each R7 is independently C1-C6 alkyl, C1-C6 heteroalkyl, C3-C8 cycloalkyl, heterocyclyl, aryl or heteroaryl; and R8 is independently hydrogen, halogen, cyano, CHF2, CF3, CO2H, amino, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 dialkylamino, aryl, CON(R7)2, C1-C6 acyl, C1-C6 heteroacyl, aroyl or heteroaroyl; or a pharmaceutically acceptable salt thereof; in combination with a therapeutically effective amount of a pharmacological agent that down-regulates or inhibits homology directed repair (HDR) of DNA to a patient in need thereof.
|
