Compositions and methods for treating cancer

A protected anti-neoplastic agent, in which the anti-neoplastic agent is an alkylating agent, and includes one or more protectable hydroxyl groups or amine groups, and wherein one or more of the protectable hydroxyl groups or amine groups is substituted with a group selected from Hyp-L- or Hyp-, wherein Hyp is a hypoxic activator having the formula

• wherein R1 is substituted or unsubstituted C1-C6 alkyl or substituted or unsubstituted C1-C6 alkoxy;
• R2 is hydrogen;
• R3 is —H or C1-C6 alkyl;
• and
• R4 is —H, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 alkoxy;
• wherein the R1 and R4 substituted alkyl and substituted alkoxy are independently substituted with one or more heteroatom-containing groups selected from ether (—OR20), amino (—NH2), mono-substituted amino (—NR20H), di-substituted amino (—NR21R22), cyclic C1-5 alkylamino, imidazolyl, C1-6 alkylpiperazinyl, morpholino, thiol (—SH), thioether —(SR20), tetrazole, carboxylic acid (—COOH), ester (—COOR20), amide (—CONH2), mono-substituted amide (—CONHR20), disubstituted amide (—CONR21R22), N-connected amide (—NH2—C(═O)—R20), mono-substituted N-connected amide (—NHR21—C(═O)—R20), disubstituted N-connected amide (—NR21R22—S(═O)2—R20), N-connected sulfonamide (—NH2—S(═O)2—R20), mono-substituted N-connected sulfonamide (—NHR21—S(═O)2—R20), disubstituted N-connected sulfonamide (—NR21R22—S(═O)2—R20), sulphoxy (—S(═O)2OH), sulphonate (S(═O)2OR20), sulphonyl (S(═O)2R20), sulphixy (S(═O)OH), sulphinate (S(═O)OR20), sulphinyl (S(═O)R20), phosphonooxy (OP(═O)(OH)2), phosphate (OP(═O)(OR20)2), and sulfonamide (—S(═O)2NH2, —S(═O)2NHR21, or —S(═O)2NR21R22), where R20, R21, and R22 are independently selected from a C1-C6 alkyl group;
• and
• L is a linking group of the formula
• where X is selected from
• wherein R6 is unsubstituted alkyl or alkyl substituted with one or more heteroatom containing groups;
• R7 is hydrogen, unsubstituted alkyl or alkyl substituted with one or more heteroatom containing groups;
• and
• Y is a spacer group selected from a substituted or unsubstituted —(CH2)n— chain with n=1-4;
• a substituted or unsubstituted —(CH2)n— chain with n=1-4 in which one of the carbon backbone chain atoms is substituted by a heteroatom containing group;
• or a delayed release group comprising an aromatic group.