Metabolically stable alkoxyalkyl esters of antiviral or antiproliferative phosphonates, nucleoside phosphonates and nucleoside phosphates

1. A nucleoside phosphonate selected from the group of compounds having the following structures:

wherein

R is selected from the group consisting of —R 1 —O—R 2 , wherein R 1 is selected from the group consisting of an optionally substituted C 1 to C 11 alkyl group and R 2 is selected from the group consisting of a C 6 to C 17 alkyl group or a C 6 to C 17 alkenyl group;

wherein

said C 6 to C 17 alkyl group is substituted with one or more alkyl groups selected from the group consisting of methyl, ethyl, propyl, or cycloalkyl, including cyclopropyl and/or one or more halogens selected from the group consisting of F, Cl, Br and I; and further wherein said C 6 to C 17 alkyl group includes one or more substituents at or near the terminal position of the alkyl group; and

wherein

said C 6 to C 17 alkenyl group is optionally-substituted with an alkyl group selected from the group consisting of methyl, ethyl, propyl, a cycloalkyl group including, cyclopropyl and/or one or more halogens selected from the group consisting of F, Cl, Br and I; and further wherein the said C 6 to C 17 alkenyl group contains one or more double bonds, including a terminal double bond;

B is selected from a purine or pyrimidine base; and

A is a counterion selected from the group consisting of H + , Li + , Na + , K + , NH 4 + , tetraalkyl ammonium and other tertiary amine salts including triethylamine.

2. The phosphonate of claim 1 wherein R is selected from the group of compounds having the following structure:

wherein p is selected from 1 to 11 and q is selected from 6 to 17.

3. The phosphonate of claim 1 wherein R is selected from the group of compounds having the following structure:

wherein p is selected from 1 to 11 and q is selected from 6 to 17.

4. The phosphonate of claim 1 wherein R is selected from the group of compounds having the following structure:

wherein p is selected from 1 to 11 and q is selected from 6 to 17 and X is a halogen.

5. The phosphonate of claim 4 wherein X is F.

6. The phosphonate of claim 1 wherein R is selected from the group of compounds having the following structure:

wherein p is selected from 1 to 11 and q is selected from 6 to 17 and X is independently selected from a halogen.

7. The phosphonate of claim 6 wherein X is F.

8. The phosphonate of claim 6 wherein R is selected from the group of compounds having the following structures:

9. The nucleoside phosphonate of claim 1 wherein R is selected to prevent or decrease metabolic degradation of the phosphonate.

10. The nucleoside phosphonate of claim 1 wherein said phosphonate is selected from a compound having the following structures:

11. The nucleoside phosphonate of claim 1 wherein said phosphonate is selected from a compound having the following structures:

12. A nucleoside phosphonate selected from the group consisting of: 3-(12-methyltridecyloxy)propyl cyclic cidofovir, 3-(13-methyltetradecyloxy)propyl cyclic cidofovir, 3-(14-methylpentadecyloxy)propyl cyclic cidofovir, 2-(17-methyloctadecyloxy)ethyl cyclic cidofovir, 3-(15-methylhexadecyloxy)propyl cyclic cidofovir, 3-(15-methylhexadecyloxy)ethyl(S)-cyclic HPMPA, 3-(15-methylhexadecyloxy)propyl(S)-cyclic HPMPA, 2-(17-methyloctadecyloxy)ethyl-(S)-cyclic HPMPA, 3-(12-methyltridecyloxy)propyl cidofovir, 3-(13-methyltetradecyloxy)propyl cidofovir, 3-(14-methylpentadecyloxy)propyl cidofovir, 3-(15-methylhexadecyloxy)propyl cidofovir, sodium, 3-(15-methylhexadecyloxy)propyl cidofovir, ammonium, 2-(17-methyloctadecyloxy)ethyl cidofovir, 2-(15-methylhexadecyloxy)ethyl cidofovir, 3-(phytanyloxy)propyl cidofovir, 3-(15-methylhexadceyloxy)ethyl-(S)-HPMPA, 2-(17-methyloctadecyloxy)ethyl-(S)-HPMPA, 3-(hex-dec-15-enyloxy)propyl cidofovir, ammonium, 3-(15-fluorohexadecyloxy)propyl cidofovir, 3-(15-fluorohexadecyloxy)propyl cyclic cidofovir, 3-(15-fluorohexadceyloxy)propyl-(S)-HPMPA, 3-(15-fluorohexadceyloxy)propyl-(S)-cyclic HPMPA, 3-(16-fluorohexadecyloxy)propyl cidofovir, 3-(16-fluorohexadecyloxy)propyl cyclic cidofovir, 3-(16-fluorohexadceyloxy)propyl-(S)-HPMPA, 3-(16-fluorohexadceyloxy)propyl-(S)-cyclic HPMPA, and 11-(7,7,8,8,8-pentafluoro-octyloxy)-undecyl cidofovir, ammonium salt.

13. The nucleoside phosphonate of claim 1 wherein said phosphonate is selected from an antiviral or an antineoplastic agent.

14. The nucleoside phosphonate of claim 13 , wherein said antiviral agent is a derivative is adefovir, cidofovir, cyclic cidofovir, tenofovir, phosphonomethyoxyethylguanine or HPMPA.

15. A pharmaceutical composition comprising a nucleoside phosphonate according to claim 1 and a pharmaceutically acceptable carrier.

16. A method for treating a viral infection, said method comprising administering to a host in need thereof an effective amount of a phosphonate compound according to claim 1 .