Nucleoside phosphoramidates
A nucleoside compound having activity against hepatitis C virus is disclosed.
1. A compound represented by formula I, or its stereoisomers, salts, or pharmaceutically acceptable salts thereof:
wherein
Z is
R 1 is hydrogen or phenyl; R 2 is hydrogen; R 3a is hydrogen; R 3b is CH 3 ; R 4 is hydrogen, i Pr, or cyclopentyl; R 5 is hydrogen; R 6 is CH 3 ; X is F; R 8 is OMe, —N(—CH 2 CH 2 CH 2 —), OBn, or OH; and R 9 is NH 2 .
2. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 1 .
3. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1 .
4. The method of treatment according to claim 3 wherein the subject is infected with hepatitis C virus.
5. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 1 .
6. A compound represented by formula I, or a stereoisomer thereof:
wherein
Z is
R 1 is hydrogen or phenyl; R 2 is hydrogen; R 3a is hydrogen; R 3b is CH 3 ; R 4 is hydrogen, i Pr, or cyclopentyl; R 5 is hydrogen; R 6 is CH 3 ; X is F; R 8 is OMe, —N(—CH 2 CH 2 CH 2 —), OBn, or OH; and R 9 is NH 2 .
7. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 6 .
8. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 6 .
9. The method of treatment according to claim 8 wherein the subject is infected with hepatitis C virus.
10. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 6 .
11. The compound of claim 1 wherein R 8 is OMe.
12. The compound of claim 11 wherein R 1 is phenyl.
13. The compound of claim 12 wherein R 4 is i Pr.
14. The compound of claim 12 wherein R 4 is cyclopentyl.
15. The compound of claim 12 wherein R 4 is hydrogen.
16. The compound of claim 11 wherein R 1 and R 4 are both hydrogen.
17. The compound of claim 1 wherein R 8 is OH.
18. The compound of claim 17 wherein R 1 is phenyl.
19. The compound of claim 18 wherein R 4 is i Pr.
20. The compound of claim 18 wherein R 4 is cyclopentyl.
21. The compound of claim 18 wherein R 4 is hydrogen.
22. The compound of claim 17 wherein R 1 and R 4 are both hydrogen.
23. A compound or its stereoisomer thereof selected from among
24. The compound of claim 23 or its stereoisomer thereof selected from among
25. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 11 .
26. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 17 .
27. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 23 .
28. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 11 .
29. The method of treatment according to claim 28 wherein the subject is infected with hepatitis C virus.
30. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 11 .
31. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 17 .
32. The method of treatment according to claim 31 wherein the subject is infected with hepatitis C virus.
33. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 17 .
34. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 23 .
35. The method of treatment according to claim 34 wherein the subject is infected with hepatitis C virus.
36. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 23 .