Methods and compositions for treating hepatitis C virus

1. A method for the treatment of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVII:

or a pharmaceutically acceptable salt or ester thereof, wherein:

Base is a purine;

R 1 and R 2 are independently H; phosphate; a stabilized phosphate prodrug; acyl; or pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1 and R 2 are independently H or phosphate;

R 6 is, alkyl,

R 7 and R 9 are independently hydrogen, OR 2 , hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chlorine, bromine, iodine, NO 2 , NH 2 , —NH(lower alkyl), —NH(acyl), —N(lower alkyl) 2 , or —N(acyl) 2 ;

R 10 is H, alkyl, chlorine, bromine or iodine;

alternatively, R 7 and R 9 , or R 7 and R 10 can come together to form a bond; and

X is O.

2. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula II:

or a pharmaceutically acceptable salt or ester thereof, wherein:

R 1 , R 2 and R 3 are independently H; phosphate or a stabilized phosphate prodrug; acyl; or pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1 , R 2 and R 3 are independently H or phosphate; and

Y is hydrogen, bromo, chloro, fluoro, iodo, OR 4 , NR 4 R 5 or SR 4 ;

X 1 and X 2 are independently selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR 4 , NR 4 NR 5 or SR 4 ; and

R 4 and R 5 are independently hydrogen, acyl, or alkyl.

3. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula X or XI:

or a pharmaceutically acceptable salt or ester thereof, wherein:

Base is a purine;

R 1 , R 2 and R 3 are independently H; phosphate or a stabilized phosphate prodrug; acyl; or pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1 , R 2 and R 3 are independently H or phosphate;

R 6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, —(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chloro, bromo, fluoro, iodo, NO 2 , NH 2 , —NH(lower alkyl), —NH(acyl), —N(lower alkyl) 2 , or —N(acyl) 2 ;

R 7 is hydrogen, OR 3 , alkyl, and

X is O.

4. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, wherein, in the compound of Formula XVII:

R 10 is H, alkyl, chlorine, bromine or iodine;

R 7 and R 9 are independently hydrogen, OR 2 , alkyl, alkenyl, alkynyl, Br-vinyl,

O-alkenyl, chlorine, bromine, iodine, NO 2 , NH 2 , —NH(lower alkyl), —NH(acyl), —N(lower alkyl) 2 , or —N(acyl) 2 ;

R 6 is alkyl, chlorine, bromine or iodine;

alternatively, R 7 and R 9 , or R 8 and R 9 can come together to form a bond; and

X is O, S, SO 2 or CH 2 .

5. The method of claim 1 wherein R 1 is hydrogen or phosphate.

6. The method of claim 1 wherein R 2 is hydrogen, of acyl.

7. The method of claim 1 wherein R 7 and R 9 are independently hydrogen, OR 2 , or hydroxy.

8. The method of claim 1 , wherein R 7 is hydroxy.

9. The method of claim 1 wherein R 9 is hydroxy.

10. The method of claim 1 wherein R 7 and R 9 are hydroxy.

11. The method of claim 1 wherein R 10 is hydrogen.

12. The method of claim 1 wherein

R 1 is hydrogen or phosphate;

R 2 is hydrogen, acyl or alkyl;

R 6 is alkyl;

R 7 and R 9 are independently hydrogen, OR 2 , or hydroxy;

R 10 is hydrogen; and

X is O.

13. The method of claim 1 , wherein the base is a purine selected from the group consisting of N 6 -alkylpurines, N 6 -acylpurines, N 6 -halopurine, N 6 -vinylpurine, N 6 -acetylenic purine, N 6 -acyl purine, N 6 -hydroxyalkyl purine, N 6 -thioalkyl purine, N 2-alkylpurines, N 2 -alkyl-6-thiopurines, N 2 -alkylpurines, N 2 -alkyl-6-thiopurines, 5-azacytidinyl, guanine, adenine, hypoxanthine, 2,6-diaminopurine, and 6-chloropurine.

14. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

15. The method of claim 1 for the treatment of a hepatitis c virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof, wherein R is hydrogen or alkyl.

16. The method of claim 15 , wherein R is methyl, ethyl, propyl, isopropyl, or cyclopropyl.

17. The method of claim 15 , wherein R is butyl, isobutyl, t-butyl, pentyl, cyclopentyl, isopentyl, or neopentyl.

18. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

19. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

20. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

21. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

22. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

23. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

24. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

25. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

26. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

or a pharmaceutically acceptable salt or ester thereof.

27. The method of claim 1 for the treatment of a hepatitis C virus infection in a host, wherein the purine base is selected from the group consisting of

wherein R

is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, cyclopentyl, isopentyl, or neopentyl.

28. The method of claim 1 , wherein the method comprises administering the compound or a pharmaceutically acceptable salt or ester thereof in combination or alternation with a second anti-hepatitis C virus agent.

29. The method of claim 28 , wherein the second anti-hepatitis C virus agent is selected from the group consisting of consisting of interferon, ribavirin, a protease inhibitor, a thiazolidine derivative, a polymerase inhibitor, and a helicase inhibitor.

30. The method of claim 29 , wherein the second anti-hepatitis C virus agent is interferon.

31. The method of claim 29 , wherein the second anti-hepatitis C virus agent is a protease inhibitor.

32. The method of claim 29 , wherein the second anti-hepatitis C virus agent is ribavirin.

33. The method of claim 1 , wherein the compound is in the form of a dosage unit.

34. The method of claim 33 , wherein the dosage unit contains 50 to 1000 mg of said compound.

35. The method of claim 33 , wherein said dosage unit is a tablet or capsule.

36. The method of claim 1 , wherein the host is a human.

37. The method of claim 1 , wherein the compound is in substantially pure form.

38. The method of claim 1 , wherein the compound is at least 90% by weight of the β-D-isomer.

39. The method of claim 1 , wherein the compound is at least 95% by weight of the β-D-isomer.