Patent ID: 7550496

Claim:
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 R 1 is substituted or unsubstituted C 1 -C 6 alkyl or substituted or unsubstituted C 1 -C 6 alkoxy; R 2 is hydrogen; R 3 is —H or C 1 -C 6 alkyl; and R 4 is —H, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 1 -C 6 alkoxy; wherein the R 1 and R 4 substituted alkyl and substituted alkoxy are independently substituted with one or more heteroatom-containing groups selected from ether (—OR 20 ), amino (—NH 2 ), mono-substituted amino (—NR 20 H), di-substituted amino (—NR 21 R 22 ), cyclic C 1-5 alkylamino, imidazolyl, C 1-6 alkylpiperazinyl, morpholino, thiol (—SH), thioether —(SR 20 ), tetrazole, carboxylic acid (—COOH), ester (—COOR 20 ), amide (—CONH 2 ), mono-substituted amide (—CONHR 20 ), disubstituted amide (—CONR 21 R 22 ), N-connected amide (—NH 2 —C(═O)—R 20 ), mono-substituted N-connected amide (—NHR 21 —C(═O)—R 20 ), disubstituted N-connected amide (—NR 21 R 22 —S(═O) 2 —R 20 ), N-connected sulfonamide (—NH 2 —S(═O) 2 —R 20 ), mono-substituted N-connected sulfonamide (—NHR 21 —S(═O) 2 —R 20 ), disubstituted N-connected sulfonamide (—NR 21 R 22 —S(═O) 2 —R 20 ), sulphoxy (—S(═O) 2 OH), sulphonate (S(═O) 2 OR 20 ), sulphonyl (S(═O) 2 R 20 ), sulphixy (S(═O)OH), sulphinate (S(═O)OR 20 ), sulphinyl (S(═O)R 20 ), phosphonooxy (OP(═O)(OH) 2 ), phosphate (OP(═O)(OR 20 ) 2 ), and sulfonamide (—S(═O) 2 NH 2 , —S(═O) 2 NHR 21 , or —S(═O) 2 NR 21 R 22 ), where R 20 , R 21 , and R 22 are independently selected from a C 1 -C 6 alkyl group; and L is a linking group of the formula where X is selected from wherein R 6 is unsubstituted alkyl or alkyl substituted with one or more heteroatom containing groups; R 7 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 —(CH 2 ) n — chain with n=1-4; a substituted or unsubstituted —(CH 2 ) 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.