Water-soluble etoposide analogs and methods of use thereof

A compound selected from the group consisting of:

• (i) compounds of Formula IIa:
• 39
• wherein:
• X is a linking group selected from the group consisting of —O—, —S—, —NH—, —CO—, —CH═N—, and CH2NH—;
• R1 is a covalent linkage between X and Y, or is loweralkyl, loweralkenyl, or phenyl, and when phenyl is unsubstituted or is substituted from one to four times with loweralkyl, hydroxy, alkoxyl, alkylogen, alkyl amino, alkyoxycarbonyl, amino, halogen, nitro, or nitrile;
• Y is none, —NHCO—, —CONH—, —OCO—, or —COO—;
• Z is —CHR2(CH2)nR3, where n is 0 to 8, or —(CH2)n— is incorporated into Z as a five-, six-, seven-, or eight-membered ring;
• R2 is H, and R3 is a loweralkyl, loweralkenyl, aryl, lower alkylamino, lower alkenylamino, or arylamino;
• or a pharmaceutically acceptable salt thereof;
• and
• (ii) compounds of Formula IIb:
• 40
• wherein:
• X is a linking group selected from the group consisting of —O—, —S—, —NH—, —CO—, —CH═N—, or CH2NH—, and in one preferred embodiment is —NH—;
• R1 is a covalent linkage between X and Z, or is loweralkyl, loweralkenyl, or phenyl, and when phenyl is unsubstituted or is substituted from one to four times with loweralkyl, hydroxy, alkoxyl, alkylogen, alkylamino, alkyoxycarbonyl, amino, halogen, nitro, or nitrile;
• Y is none, —NHCO—, —CONH—, —OCO—, or —COO—;
• Z is —(CH2)nR3, where n is 0 to 8, or —(CH2)n— is incorporated into Z as a five-, six-, seven-, or eight-membered ring,. R3 is a loweralkyl, loweralkenyl, aryl, lower alkylamino, lower alkenylamino, or arylamino;
• R12 is —OR4, —NR4R5, —OCOR4, —OCOOR4, —OCOSR4, or —OCONR4R5, where R4 and R5 are selected from the group consisting of lower alkylamino, lower alkenylamino, and arylamino;
• or a pharmaceutically acceptable salt thereof.