Nucleoside phosphoramidate prodrugs
Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.
1. A compound represented by the following formula:
wherein
(a) R 1 is phenyl;
(b) R 2 is hydrogen;
(c) R 3a is CH 3 ;
(d) R 3b is H;
(e) R 4 is t Pr, n Pr, n Bu, 2-butyl, t Bu, or benzyl;
(f) R 5 is H;
(g) R 6 is CH 3 ;
(h) X is F;
(i) Y is OH;
(j) R 7 is H; and
(k) R 8 is H.
2. The compound of claim 1 , having the following structure:
3. The compound of claim 1 , having the following structure:
4. The compound of claim 1 , having the following structure:
5. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient.
6. A method of treating HCV comprising administering a therapeutically effective amount of a compound according to claim 1 to a human subject in need thereof.
7. The method of claim 6 further comprising administering to the human subject a therapeutically effective amount of a second antiviral agent.
8. The method of claim 7 wherein the second antiviral agent is an NS5A inhibitor.
9. The method of claim 7 wherein the second antiviral agent is an NS3 protease inhibitor.
10. The method of claim 6 further comprising administering to the human subject therapeutically effective amounts of an NS5A inhibitor and an NS3 protease inhibitor.