Phosphoramidate alkylator prodrugs

A compound of formula (I):

• wherein
• Y1 is O, S, NR6 or NSO2R6
• Y2 is O, S, NR6, NCOR6, or NSO2R6 wherein each R6 is independently (C1-C6)alkyl, C1-C6 heteroalkyl, aryl, or heteroaryl;
• R1 is a Trigger, T, having the formula L-Z3;
• L is selected from the group consisting of:
• —[C(Z1)2—Y3]v—[C(═O)—O)]q—[C(Z 1)2—Z2—Y4]u—[C(Z1)2]Z—[C(Z1)═C(Z1)]g;
• —[C(Z1)2—Y3]v—(S(═O)2)q—[C(Z1)2—Z2—Y4]u—[C(Z1)2]Z—[C(Z1)═C(Z1)]g;
• —[C(Z1)2—Y3]—[C(Z1)2—Z2—Y4]—[C(Z1)2]Z—[C(Z1)═C(Z1)]—;
• —[C(Z1)2—Y3]—[C(Z1)2]z—[C(Z1)═C(Z1)]—;
• —[C(Z1)2—Y3]—[C(Z1)2]Z—;
• —[C(Z1)2—Y3]—(C(═O)—O)—[C(Z1)2]Z—[C(Z1)═C(Z1)]—;
• —[C(Z1)2—Y3]—(C(═O)—O)—[C(Z1)2]Z—;
• —[C(Z1)2—Y3]—(C(═O)—O)—[C(Z1)2]Z—[C(Z1)═C(Z1)]—;
• —[C(Z1)2—Z2—Y4]—[C(Z1)2]Z—[C(Z1)═C(Z1)]—;
• —[C(Z1)2]Z—[C(Z1)═C(Z1)]—;
• and
• —[C(Z1)2]Z:
• wherein each z, v, q, u, and g independently is 0 or 1;
• Y3 is S, O, or NR7 wherein each R7 is independently hydrogen, hydroxyl, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C8 cycloalkyl, heterocyclyl, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 dialkylamino, aryl, heteroaryl, C1-C6 acyl, C1-C6heteroacyl, aroyl, or heteroaroyl;
• Y4 is O, S, or —NR7—C(═O)—O—;
• each Z1 independently is hydrogen, halogen, C1-C6 alkyl, C1-C6 heteroalkyl, aryl, heteroaryl, C3-C8 cycloalkyl, heterocyclyl, C1-C6 acyl, C1-C6heteroacyl, aroyl, or heteroaroyl;
• Z2 is C1-C6alkylene, C1-C6 heteroalkylene,
• wherein each X1 is independently N or CR8 wherein R8 is independently hydrogen, OH, OP(═O)(OH)2, halogen, nitro, cyano, CHF2, CF3, CH2CF3, CO2H, amino, C1-C6 alkyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 dialkylamino, aryl, CON(R7)2, C1-C6 acyl, C1-C6heteroacyl, aroyl or heteroaroyl;
• X2 is NR7, S, or O;
• and
• Z3 is a bioreductive group having a formula selected from the group consisting of:
• with the proviso that in formula (I):
• (a) NR2R3 is NHR3;
• NR4R5 is NHR5 and R3 and R5 independently are selected from the group consisting of 2-haloalkyl, 2- C1-C6 alkylsulfonyloxyalkyl, heteroalkylsulfonyloxyalkyl, 2-arylsulfonyloxyalkyl, and 2-heteroarylsulfonyloxyalkyl;
• (b) NR2R3 is NHR3;
• and R3 independently is selected from the group consisting of 2-haloalkyl, 2-C1-C6 alkylsulfonyloxyalkyl, 2-heteroalkylsulfonyloxyalkyl 2-arylsulfonyloxyalkyl, and 2 -heteroarylsulfonyloxyalkyl;
• and NR4R5 is
• or
• (c) NR2R3 and NR4R5 are
• an individual stereoisomer or a racemic or non-racemic mixture of stereoisomers, or a pharmaceutically acceptable salt, solvate, or hydrate, thereof.