Synergistically effective combinations of dihaloacetamide compounds and interferon or ribavirin against HCV infections

1. A method of treating an HCV infection comprising adjunctively administering to a subject a synergistically effective amount of a combination comprising an anti-HCV dihaloacetamide compound with an interferon and/or a ribavirin.

2. The method of claim 1 in which the interferon is an alpha-interferon.

3. The method of claim 2 in which the alpha interferon is IFNα-1a or IFNα-1b.

4. The method of claim 1 in which the interferon is interferon alpha-n1 (INS).

5. The method of claim 1 in which the interferon is β-interferon or an ω-interferon.

6. The method of claim 1 in which the interferon comprises a pegylated interferon.

7. The method of claim 6 in which the pegylated interferon is pegylated interferon-2b, pegylated interferon-2a or a combination thereof.

8. The method of claim 1 in which the ribavirin has the structure 1-β-D-ribofuranosyl-1,2,4-triazole.

9. The method of claim 1 in which the combination includes both the interferon and the ribavirin.

10. The method of any one of claims 1 - 9 in which the anti-HCV dihaloacetamide compound is compound I:

11. The method of any one of claims 1 - 9 in which the anti-HCV dihaloacetamide compound is compound II:

12. The method of any one of claims 1 - 9 in which the anti-HCV dihaloacetamide compound is a mixture of compound I:

and compound II:

13. The method of claim 1 in which the anti-HCV dihaloacetamide compound, interferon and/or ribavirin are administered simultaneously.

14. The method of claim 1 in which the anti-HCV dihaloacetamide compound, interferon and/or ribavirin are administered sequentially in any order.

15. A method of inhibiting HCV replication comprising contacting an HCV virion with a synergistically effective combination comprising an anti-HCV dihaloacetamide compound, an interferon and/or a ribavirin.

16. The method of claim 1 wherein the anti-HCV dihaloacetamide compound is of the following structural formula:

or a pharmaceutically acceptable salt, hydrate, solvate, or N-oxide thereof, wherein:

R 2 and R 6 are independently selected from the group consisting of hydrogen, halo, C 1 -C 15 alkyl, substituted C 1 -C 15 alkyl, C 1 -C 15 alkylthio, substituted C 1 -C 15 alkylthio, alkoxy, substituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, aryl-C 1 -C 15 alkyloxycarbonyl, substituted aryl-C 1 -C 15 alkyloxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, cycloheteroalkyl, substituted cycloheteroalkyl, carbamoyl, substituted carbamoyl, halo-C 1 -C 15 alkyl, sulfamoyl, substituted sulfamoyl, and silyl ethers, provided that at least one of R 2 and R 6 is other than hydrogen;

R 3 and R 5 are independently selected from the group consisting of hydrogen, halo, C 1 -C 15 alkyl, substituted C 1 -C 15 alkyl, C 1 -C 15 alkylthio, substituted C 1 -C 15 alkylthio, alkoxy, substituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, aryl-C 1 -C 15 alkyloxycarbonyl, substituted aryl-C 1 -C 15 alkyloxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, cycloheteroalkyl, substituted cycloheteroalkyl, carbamoyl, substituted carbamoyl, halo-C 1 -C 15 alkyl, sulfamoyl, and substituted sulfamoyl;

R 4 is selected from the group consisting of hydrogen, halo, C 1 -C 15 alkyl, substituted C 1 -C 15 alkyl, C 1 -C 15 alkylthio, substituted C 1 -C 15 alkylthio, carbamoyl, substituted carbamoyl, alkoxy, substituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, aryl-C 1 -C 15 alkyloxycarbonyl, substituted aryl-C 1 -C 15 alkyloxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, di-C 1 -C 15 alkylamino, substituted di-C 1 -C 15 alkylamino, halo-C 1 -C 15 alkylamino, sulfamoyl, and substituted sulfamoyl;

R 8 , R 9 , and R 14 are independently selected from the group consisting of hydrogen, halo, and fluoro;

R 11 is hydrogen, or C 1 -C 15 alkyl; and

R 12 is selected from the group consisting of substituted C 1 -C 15 alkyl, halo-C 1 -C 15 alkyl, cycloheteroalkyl, and substituted cycloheteroalkyl.