Nucleoside cyclicphosphates
Cyclic phosphate of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof, represented by the following structure:
1. A compound or a salt thereof having the structure:
2. A composition comprising the compound or a salt thereof as claimed in claim 1 and optionally a pharmaceutically acceptable medium.
3. A composition for the treatment of hepatitis C virus comprising the compound or a salt thereof as claimed in claim 1 and a pharmaceutically acceptable medium.
4. A composition for the treatment of hepatitis C virus comprising an effective amount of the compound or a salt thereof as claimed in claim 1 and a pharmaceutically acceptable medium.
5. A method of treating a subject infected with a virus, which comprises:
administering to the subject an effective amount of the compound or salt thereof as claimed in claim 1 ;
wherein the virus is selected from among hepatitis C virus, West Nile virus, a yellow fever virus, a dengue virus, a rhinovirus, a polio virus, a hepatitis A virus, a bovine viral diarrhea virus, and a Japanese encephalitis virus.
6. A method of treating a hepatitis C virus infection in a subject, which comprises:
administering to the subject an effective amount of the compound or salt thereof as claimed in claim 1 .
7. The method as claimed in claim 6 , wherein the subject is a human.
8. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound or a salt thereof as claimed in claim 1 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor, an HCV NS5B inhibitor, an HCV NS4 inhibitor, and an HCV NS5a inhibitor; and
a pharmaceutically acceptable medium.
9. A method of treating a hepatitis C virus infection in a subject, which comprises:
administering to the subject the composition as claimed in claim 8 .
10. The method as claimed in claim 9 , wherein the subject is a human.
11. A compound or a salt thereof having the structure:
12. A composition comprising the compound or a salt thereof as claimed in claim 11 and optionally a pharmaceutically acceptable medium.
13. A composition for the treatment of hepatitis C virus comprising the compound or a salt thereof as claimed in claim 11 and a pharmaceutically acceptable medium.
14. A composition for the treatment of hepatitis C virus comprising an effective amount of the compound or a salt thereof as claimed in claim 11 and a pharmaceutically acceptable medium.
15. A method of treating a subject infected by a virus, which comprises:
administering to the subject an effective amount of the compound or salt thereof as claimed in claim 11 ;
wherein the virus is selected from among hepatitis C virus, West Nile virus, a yellow fever virus, a dengue virus, a rhinovirus, a polio virus, a hepatitis A virus, a bovine viral diarrhea virus, and a Japanese encephalitis virus.
16. A method of treating a hepatitis C virus infection in a subject, which comprises:
administering to the subject an effective amount of the compound or salt thereof as claimed in claim 11 .
17. The method as claimed in claim 16 , wherein the subject is a human.
18. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound or a salt thereof as claimed in claim 11 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor, an HCV NS5B inhibitor, an HCV NS4A inhibitor, an HCV NS4B inhibitor, and an HCV NS5A inhibitor; and
a pharmaceutically acceptable medium.
19. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound or a salt thereof as claimed in claim 11 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor, an HCV NS5B inhibitor, and an HCV NS5A inhibitor; and
a pharmaceutically acceptable medium.
20. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound or a salt thereof as claimed in claim 11 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor and an HCV NS5B inhibitor; and
a pharmaceutically acceptable medium.
21. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound or a salt thereof as claimed in claim 11 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor and an HCV NS5A inhibitor; and
a pharmaceutically acceptable medium.
22. A method of treating a hepatitis C virus infection in a subject, which comprises: administering to the subject the composition as claimed in any one of claims 18 - 21 .
23. The method as claimed in claim 22 , wherein the subject is a human.
24. A compound having the structure:
25. A composition comprising the compound as claimed in claim 24 and optionally a pharmaceutically acceptable medium.
26. A composition for the treatment of hepatitis C virus comprising the compound as claimed in claim 24 and a pharmaceutically acceptable medium.
27. A composition for the treatment of hepatitis C virus comprising an effective amount of the compound as claimed in claim 24 and a pharmaceutically acceptable medium.
28. A method of treating a subject infected by a virus, which comprises:
administering to the subject an effective amount of the compound as claimed in claim 24 ;
wherein the virus is selected from among hepatitis C virus, West Nile virus, a yellow fever virus, a dengue virus, a rhinovirus, a polio virus, a hepatitis A virus, a bovine viral diarrhea virus, and a Japanese encephalitis virus.
29. A method of treating a hepatitis C virus infection in a subject, which comprises:
administering to the subject an effective amount of the compound as claimed in claim 24 .
30. The method as claimed in claim 29 , wherein the subject is a human.
31. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound as claimed in claim 24 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor, an HCV NS5B inhibitor, an HCV NS4A inhibitor, an HCV NS4B inhibitor, and an HCV NS5A inhibitor; and
a pharmaceutically acceptable medium.
32. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound as claimed in claim 24 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor, an HCV NS5B inhibitor, and an HCV NS5A inhibitor; and
a pharmaceutically acceptable medium.
33. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound as claimed in claim 24 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor and an HCV NS5B inhibitor; and
a pharmaceutically acceptable medium.
34. A composition for the treatment of hepatitis C virus comprising:
an effective amount of the compound as claimed in claim 24 ;
an effective amount of at least one agent selected from among an HCV NS3 protease inhibitor and an HCV NS5A inhibitor; and
a pharmaceutically acceptable medium.
35. A method of treating a hepatitis C virus infection in a subject, which comprises:
administering to the subject the composition as claimed in claim in any one of claims 31 - 34 .
36. The method as claimed in claim 34 , wherein the subject is a human.
37. A compound or a salt thereof having the structure:
38. A composition comprising the compound or a salt thereof as claimed in claim 37 and optionally a pharmaceutically acceptable medium.
39. A composition for the treatment of hepatitis C virus comprising the compound or a salt thereof as claimed in claim 37 and a pharmaceutically acceptable medium.
40. A compound or a salt thereof having the structure:
41. A composition comprising the compound or a salt thereof as claimed in claim 40 and optionally a pharmaceutically acceptable medium.
42. A composition for the treatment of hepatitis C virus comprising the compound or a salt thereof as claimed in claim 40 and a pharmaceutically acceptable medium.
43. A process for preparing the compound or a salt thereof as claimed in claim 1 , said process comprising reacting compound 16 having the structure
with i PrOP(N i Pr 2 ) 2 in the presence of a base to obtain compound 16′ having the structure,
and
reacting compound 16′ with an oxidant to obtain the compound or a salt thereof.
44. The process as claimed in claim 43 , which further comprises separating the individual diastereomers of the compound or a salt thereof.
45. A composition comprising the compound or a salt thereof as obtained by the process as claimed in claim 43 .
46. A composition comprising the compound or a salt thereof as obtained by the process as claimed in claim 44 .