2′-chloro nucleoside analogs for HCV infection

1. A compound according to Formula 2001:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof, wherein:

B is

 and

PD is monophosphate, diphosphate, or triphosphate; and Z is —OH; or

PD is

 W is O; Z and Y join to form a six-membered heterocyclic ring wherein Z and Y together represent a single divalent —O—; and X is an N-linked amino acid ester.

2. The compound of claim 1 according to Formula II:

wherein X is an N-linked D-amino acid ester; or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

3. The compound of claim 2 wherein each X is independently an N-linked D-alanine ester.

4. The compound of claim 2 , wherein said compound is according to one of the following the structures:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

5. The compound according to claim 4 , wherein said compound is selected from the group consisting of:

6. The compound of claim 1 according to Formula (2001) wherein PD is monophosphate, diphosphate, or triphosphate; or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

7. The compound of claim 1 which is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

8. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof, wherein:

PD is

and

a pharmaceutically acceptable excipient, carrier or diluent.

9. The pharmaceutical composition of claim 8 , wherein said compound is

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

10. The pharmaceutical composition of claim 9 , wherein said compound is:

11. The pharmaceutical composition according to claim 8 , wherein said compound is selected from the group consisting of:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof, said compound is a designated enantiomer and said composition is substantially free of stereoisomers of said designated enantiomer.

12. The pharmaceutical composition according to claim 11 , wherein said compound is a designated enantiomer selected from the group consisting of:

and said composition is substantially free of stereoisomers of said designated enantiomer.

13. A method of treating an hepatitis C virus (HCV) in a human infected with an HCV, comprising administering to the human an effective amount of the compound of claim 1 .

14. The method of claim 13 where said compound is according to one of the following structures:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

15. The method according to claim 14 , wherein said compound is according to one of the following structures:

16. The method of claim 13 , wherein said compound is

17. The method of claim 13 , wherein the compound is administered in combination or alternation with a second anti-viral agent selected from the group consisting of an interferon, a nucleotide analogue, a polymerase inhibitor, an NS3 protease inhibitor, an NS5A inhibitor, an entry inhibitor, a non-nucleoside polymerase inhibitor, a cyclosporine immune inhibitor, an NS4A antagonist, an NS4B-RNA binding inhibitor, a locked nucleic acid mRNA inhibitor, and a cyclophilin inhibitor, or a combination thereof.

18. A compound according to Formula III:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof;

wherein B is uracil, adenine or guanine;

Y is OR 1 ;

R 1 is phenyl;

X is an N-linked amino acid ester; and

W is O.

19. The compound according to claim 18 , wherein said compound is according to the structure:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

20. The compound according to claim 19 , wherein said compound is according to the structure:

21. The compound according to claim 19 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

22. The compound according to claim 21 , wherein said compound is:

23. The compound according to claim 18 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

24. The compound of claim 23 , wherein said compound is:

25. The compound according to claim 18 , wherein said compound is according to the structure:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

26. The compound according to claim 25 , wherein said compound is according to the structure:

27. The compound according to claim 18 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

28. The compound according to claim 27 , wherein said compound is:

29. The compound according to claim 18 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

30. The compound of claim 29 , wherein said compound is:

31. The pharmaceutical composition according to claim 30 , wherein said compound is a designated enantiomer, and said composition is substantially free of other stereoisomers of said compound.

32. A nucleoside composition comprising a compound selected from the group consisting of:

wherein said compound is a designated enantiomer and said composition is substantially free of other stereoisomers of said compound.

33. A nucleoside composition comprising a compound selected from the group consisting of:

wherein said compound is a designated enantiomer and said composition is substantially free of other stereoisomers of said compound.

34. A pharmaceutical composition comprising a compound according to the structure:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof; and a pharmaceutically acceptable carrier.

35. The pharmaceutical composition according to claim 34 , wherein said compound is according to the structure:

36. The pharmaceutical composition according to claim 34 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

37. The pharmaceutical composition according to claim 36 , wherein said compound is:

38. A pharmaceutical composition comprising a compound according to the structure:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

39. The pharmaceutical composition according to claim 38 , wherein said compound is according to the structure:

40. The pharmaceutical composition according to claim 38 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

41. The pharmaceutical composition according to claim 40 , wherein said compound is:

42. The pharmaceutical composition according to claim 41 , wherein said compound is a designated enantiomer, and said composition is substantially free of other stereoisomers of said compound.

43. A method of treating an hepatitis C virus (HCV) in a human infected with a an HCV, comprising administering to the human an effective amount of a compound according to the structure:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

44. The method according to claim 43 , wherein said compound is according to the structure:

45. The method according to claim 43 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

46. The method according to claim 45 , wherein said compound is:

47. The method according to claim 43 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

48. The method according to claim 47 , wherein said compound is:

49. The method of claim 43 , wherein the compound is administered in combination with or in alternation with a second anti-viral agent selected from the group consisting of an interferon, a nucleotide analogue, a polymerase inhibitor, an NS3 protease inhibitor, an NSSA inhibitor, an entry inhibitor, a non-nucleoside polymerase inhibitor, a cyclosporine immune inhibitor, an NS4A antagonist, an NS4B-RNA binding inhibitor, a locked nucleic acid mRNA inhibitor, a cyclophilin inhibitor, and combinations thereof.

50. The method of claim 49 , wherein said second anti-viral agent is an NS3 protease inhibitor.

51. The method of claim 49 , wherein said second anti-viral agent is an NS5A inhibitor.

52. A method of treating an hepatitis C virus (HCV) in a human infected with a an HCV, comprising administering to the human an effective amount of a compound according to the structure:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

53. The method according to claim 52 , wherein said compound is according to the structure:

54. The method according to claim 52 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

55. The method according to claim 54 , wherein said compound is:

56. The method according to claim 52 , wherein said compound is:

or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof.

57. The method according to claim 56 , wherein said compound is:

58. The method of claim 52 , wherein the compound is administered in combination with or in alternation with a second anti-viral agent selected from the group consisting of an interferon, a nucleotide analogue, a polymerase inhibitor, an NS3 protease inhibitor, an NS5A inhibitor, an entry inhibitor, a non-nucleoside polymerase inhibitor, a cyclosporine immune inhibitor, an NS4A antagonist, an NS4B-RNA binding inhibitor, a locked nucleic acid mRNA inhibitor, a cyclophilin inhibitor, and combinations thereof.

59. The method of claim 58 , wherein said second anti-viral agent is an NS3 protease inhibitor.

60. The method of claim 58 , wherein said second anti-viral agent is an NS5A inhibitor.