Prodrugs for selective anticancer therapy

1. A compound having the structure:

wherein

X is a chemotherapeutic agent,

wherein the chemotherapeutic agent is a nucleoside or deoxynucleoside;

Y is a chemical linker,

wherein Y is absent;

Z is CH 3 or CF 3 ;

R 1 is —NR 2 R 3 , —NH—C(═O)—R 4 or —NH—C(═O)—OR 4 ,

wherein R 2 , R 3 and R 4 , are each, independently, —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, an amino acid or an oligopeptide;

wherein the amine of the amino acid or oligopeptide is substituted or unsubstituted; and

n is 4,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

2. The compound of claim 1 having the structure:

wherein

X is a chemotherapeutic agent containing at least one amine nitrogen and the amine nitrogen on the chemotherapeutic agent covalently bonds directly to carbon α,

wherein the chemotherapeutic agent is a nucleoside or deoxynucleoside;

Z is CH 3 or CF 3 ;

R 1 is —NR 2 R 3 , —NH—C(═O)—R 4 or —NH—C(═O)—OR 4 ,

wherein R 2 , R 3 and R 4 , are each, independently, —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, an amino acid or an oligopeptide;

wherein the amine of the amino acid or oligopeptide is substituted or unsubstituted; and

n is 4,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

3. The compound of claim 2 having the structure:

wherein

X is a chemotherapeutic agent containing at least one amine nitrogen and the amine nitrogen on the chemotherapeutic agent covalently bonds directly to carbon α,

wherein the chemotherapeutic agent is a nucleoside or deoxynucleoside;

Z is CH 3 or CF 3 ;

R 1 is —NR 2 R 3 , —NH—C(═O)—R 4 or —NH—C(═O)—OR 4 ,

wherein R 2 , R 3 and R 4 , are each, independently, —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, an amino acid or an oligopeptide;

wherein the amine of the amino acid or oligopeptide is substituted or unsubstituted; and

n is 4,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

4. The compound of claim 2 having the structure:

wherein

X is a chemotherapeutic agent containing at least one amine nitrogen and the amine nitrogen on the chemotherapeutic agent covalently bonds directly to carbon α,

wherein the chemotherapeutic agent is a nucleoside or deoxynucleoside;

Z is CH 3 or CF 3 ;

R 1 is —NR 2 R 3 , —NH—C(═O)—R 4 or —NH—C(═O)—OR 4 ,

wherein R 2 , R 3 and R 4 are each, independently, —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, an amino acid or an oligopeptide;

wherein the amine of the amino acid or oligopeptide is substituted or unsubstituted; and

n is 4,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

5. The compound of claim 2 ,

wherein R 1 is

wherein R 10 is —H, —CH 3 , Ac, —C(O)-Ot-Bu, —C(O)—OCH 2 Ph, —CHO, phenyl, or benzyl,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of compound.

6. The compound of claim 2 ,

wherein X is puromycin, 5-fluorocytidine, 2′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorocytidine, gemcitabine, cytarabine, cladribine, troxacitabine, azacitidine, clofarabine, decitabine, fludarabine, fludarabine phosphate, gemcitabine hydrochloride, or nelarabine,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

7. The compound of claim 2 having the structure:

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

8. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

9. The compound of claim 2 ,

wherein X is puromycin, 5-fluorocytidine, 2′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorocytidine, gemcitabine or cytarabine,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

10. The compound of claim 1 ,

wherein R 1 is

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

11. The compound of claim 1 ,

wherein

R 1 is —NHBoc;

n is 4;

X is puromycin or 5-fluorocytidine; and

Z is CH 3 ,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

12. The compound of claim 1 ,

wherein Z is CF 3 ,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

13. A compound having the structure:

wherein

X is a chemotherapeutic agent,

wherein the chemotherapeutic agent is a nucleoside or deoxynucleoside;

Y is a chemical linker,

wherein Y is absent;

Z is CH 3 or CF 3 ;

R 3 is —NR 2 R 3 ,

wherein

R 2 is —H; and

R 3 is an amino acid or oligonucleotide,

wherein the amino acid is bonded to the nitrogen through an amide bond, or

R 1 is

wherein R 8 and R 9 are each independently —H, —CH 3 , t-butyl, phenyl, or benzyl; and

n is 4,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

14. The compound of claim 13 having the structure:

wherein

X is a chemotherapeutic agent,

wherein the chemotherapeutic agent is a nucleoside or deoxynucleoside;

Y is a chemical linker,

wherein Y is absent;

Z is CH 3 or CF 3 ;

R 1 is —NR 2 R 3 ,

wherein

R 2 is —H; and

R 3 is an amino acid or oligonucleotide,

wherein the amino acid is bonded to the nitrogen through an amide bond, or

R 1 is

wherein R 8 and R 9 are each independently —H, —CH 3 , t-butyl, phenyl, or benzyl; and

n is 4,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

15. The compound of claim 13 having the structure:

wherein

X is a chemotherapeutic agent,

wherein the chemotherapeutic agent is a nucleoside or deoxynucleoside;

Y is a chemical linker,

wherein Y is absent;

Z is CH 3 or CF 3 ;

R 1 is —NR 2 R 3 ,

wherein

R 2 is —H; and

R 3 is an amino acid or oligonucleotide,

wherein the amino acid is bonded to the nitrogen through an amide bond, or

R 1 is

wherein R 8 and R 9 are each independently —H, —CH 3 , t-butyl, phenyl, or benzyl; and

n is 4,

or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

16. A pharmaceutical composition comprising the compound of claim 7 and a pharmaceutically acceptable carrier.