β-D-2′-deoxy-2′-α-fluoro-2′-β-C-substituted-2-modified-N6-substituted purine nucleotides for HCV treatment
A compound of the structure: or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to an HCV virus or other disorders more fully described herein.
1. A compound of Formula:
or a pharmaceutically acceptable salt thereof, wherein:
Y is NR 1 R 2 ;
R 1 is methyl;
R 2 is hydrogen;
R 3 is hydrogen; and
R 4 is a thiophosphoramidate.
2. The compound of claim 1 , wherein the thiophosphoramidate is of the formula:
wherein:
R P1 is an aryl, heteroaryl or heterocyclic group;
R P2 is
R 16 is hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 8 cycloalkyl)C 0 -C 4 alkyl-, (aryl)C 0 -C 4 alkyl-, (C 3 -C 6 heterocyclo)C 0 -C 4 alkyl-, or (heteroaryl)C 0 -C 4 alkyl-;
R 17 is hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 8 cycloalkyl)C 0 -C 4 alkyl-, (aryl)C 0 -C 4 alkyl-, (C 3 -C 6 heterocyclo)C 0 -C 4 alkyl-, or (heteroaryl)C 0 -C 4 alkyl-;
R 18 is hydrogen or C 1 -C 3 alkyl; and
R 19 is, (C 1 -C 6 )alkyl, (C 3 -C 6 )alkenyl, (C 3 -C 6 )alkynyl, (C 3 -C 8 cycloalkyl)C 0 -C 4 alkyl-, (aryl)C 0 -C 4 alkyl-, or (heteroaryl)C 0 -C 4 alkyl-.
3. The compound of claim 2 , wherein R P1 is phenyl.
4. The compound of claim 2 , wherein R P1 is naphthyl.
5. The compound of claim 2 , wherein R 16 is hydrogen.
6. The compound of claim 2 , wherein R 17 is methyl.
7. The compound of claim 2 , wherein R 16 is methyl.
8. The compound of claim 2 , wherein R 17 is hydrogen.
9. The compound of claim 2 , wherein R 19 is (C 1 -C 6 )alkyl.
10. The compound of claim 2 , wherein R 18 is hydrogen.
11. The compound of claim 1 , of the formula:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 11 , of the formula
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 11 of the formula:
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 1 , of the formula:
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 14 , of the formula:
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 14 , of the formula:
or a pharmaceutically acceptable salt thereof.
17. The compound of claim 1 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 1 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 1 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
20. The compound of claim 1 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
21. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
22. The pharmaceutical composition of claim 21 , in a solid dosage form.
23. The pharmaceutical composition of claim 22 , wherein the solid dosage form is an oral dosage form.
24. The pharmaceutical composition of claim 23 , wherein the oral dosage form is a tablet.
25. The pharmaceutical composition of claim 23 , wherein the oral dosage form is a capsule.
26. A method of treating a hepatitis C infection comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a human in need thereof.
27. The method of claim 26 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
28. The method of claim 27 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
29. The method of claim 27 , wherein the compound is
or a pharmaceutically acceptable salt thereof.