Targeted Delivery and Prodrug Designs for Platinum-Acridine Anti-Cancer Compounds and Methods Thereof

12) A method of treating cancer comprising administering to a subject in need thereof an effective amount of the compound of Formula I:

• wherein X is halo, OC(O)R9, nitrate or sulfate;
• R1 and R2 are amino groups or together with the platinum atom to which they are attached, R1 and R2 form the ring —NH2—(CH2)v—NH2— wherein v is 1, 2, 3, or 4 or R1 and R2 together can be any of the following groups a-h;
• wherein A is H, —CH3, —OCH3, CF3 or NO2;
• R3 is —N(R6)—;
• wherein R6 is hydrogen or C1-C6alkyl;
• R4 is independently an amino, a nitro, —NHC(O)(R10), —NHC(O)O(R10), —C(O)NHR10, —OC(O)NHR10, or halo;
• R10 is hydrogen, C1-6 alkyl, phenyl, naphthyl, C3-6 cycloalkyl, norbornyl, or adamantyl;
• q is 0, 1, or 2;
• R5 is a direct bond, —NH— or C1-C6alkylene;
• or R5 and X together with the atoms to which they are attached form a 6- or 7-membered ring, wherein said 6- or 7-membered ring contains a linking group —C(O)O— or —OC(O)—;
• R7 is hydrogen, methyl, or —C(O)O—R8;
• wherein
• R8 is hydrogen, C1-6 alkyl, phenyl, naphthyl, C3-6 cycloalkyl, norbornyl, adamantyl, a natural or unnatural amino acid or a peptide;
• R9 is hydrogen, C1-6 alkyl, phenyl, naphthyl, C3-6 cycloalkyl, norbornyl, adamantyl, a natural or unnatural amino acid or a peptide;
• either or both of R11 and R12 contain a reactive group on to which a linker and/or one or more of compound W can be added;
• and if only one of R11 and R12 contains a reactive group, then the other of R11 and R12 is hydrogen;
• compound W is one or more amino acids, one or more sugars, polymeric ethers, C1-6alkylene-phenyl-NH—C(O)—R15, folic acid, αvβ3, integrin RGD binding peptide, tamoxifen, endoxifen, EGFR (epidermal growth factor receptor) antibody conjugates, kinase inhibitors, diazoles, triazoles, oxazoles, erlotinib, and mixtures thereof,
• wherein R15 is a peptide;
• Y is C1-C6alkyl;
• and
• Z is one or more counterions sufficient to balance the charge of the compound.

20) A pharmaceutical composition comprising the compound of Formula I:

• wherein X is halo, OC(O)R9, nitrate or sulfate;
• R1 and R2 are amino groups or together with the platinum atom to which they are attached, R1 and R2 form the ring —NH2—(CH2)v—NH2— wherein v is 1, 2, 3, or 4 or R1 and R2 together can be any of the following groups a-h;
• wherein A is H, —CH3, —OCH3, CF3 or NO2;
• R3 is —N(R6)—;
• wherein R6 is hydrogen or C1-C6alkyl;
• R4 is independently an amino, a nitro, —NHC(O)(R10), —NHC(O)O(R10), —C(O)NHR10, —OC(O)NHR10, or halo;
• R10 is hydrogen, C1-6 alkyl, phenyl, naphthyl, C3-6 cycloalkyl, norbornyl, or adamantyl;
• q is 0, 1, or 2;
• R5 is a direct bond, —NH— or C1-C6alkylene;
• or R5 and X together with the atoms to which they are attached form a 6- or 7-membered ring, wherein said 6- or 7-membered ring contains a linking group —C(O)O— or —OC(O)—;
• R7 is hydrogen, methyl, or —C(O)O—R8;
• wherein
• R8 is hydrogen, C1-6 alkyl, phenyl, naphthyl, C3-6 cycloalkyl, norbornyl, adamantyl, a natural or unnatural amino acid or a peptide;
• R9 is hydrogen, C1-6 alkyl, phenyl, naphthyl, C3-6 cycloalkyl, norbornyl, adamantyl, a natural or unnatural amino acid or a peptide;
• either or both of R11 and R12 contain a reactive group on to which a linker and/or one or more of compound W can be added;
• and if only one of R11 and R12 contains a reactive group, then the other of R11 and R12 is hydrogen;
• compound W is one or more amino acids, one or more sugars, polymeric ethers, C1-6alkylene-phenyl-NH—C(O)—R15, folic acid, αvβ3 integrin ROD binding peptide, tamoxifen, endoxifen, EGFR (epidermal growth factor receptor) antibody conjugates, kinase inhibitors, diazoles, triazoles, oxazoles, erlotinib, and mixtures thereof;
• wherein R15 is a peptide;
• Y is C1-C6alkyl;
• and
• Z is one or more counterions sufficient to balance the charge of the compound;
• and a pharmaceutically acceptable diluent, carrier, or excipient.