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 of formula:
wherein
R 4 is C 1-4 alkyl;
R 10 is NH 2 , —NHR′, or —NR′ 2 ;
R 11 is H, —OH, or —NH 2 ; and
R′ is C 1-4 alkyl, or alternatively, in the instance of —NR′ 2 , each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 11 is —NH 2 .
3. The compound of claim 2 , wherein R 10 is —NHR′ or —NR′ 2 .
4. The compound of claim 3 , wherein R 10 is —NHR′.
5. The compound of claim 4 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, or t-butyl.
6. The compound of claim 4 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, or i-butyl.
7. The compound of claim 4 , wherein R′ is methyl.
8. A compound of formula:
wherein
R 4 is CH 3 , Et, iPr, n Bu, or cyclohexyl;
R 10 is NH 2 , —NHR′, or —NR′ 2 ;
R 11 is H, —OH, or —NH 2 ; and
R′ is C 1-4 alkyl, or alternatively, in the instance of —NR′ 2 , each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms;
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 8 , wherein R 11 is —NH 2 .
10. The compound of claim 9 , wherein R 10 is —NHR′ or —NR′ 2 .
11. The compound of claim 10 , wherein R 10 is —NHR′.
12. The compound of claim 11 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, or t-butyl.
13. The compound of claim 11 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, or i-butyl.
14. The compound of claim 11 , wherein R′ is methyl.
15. A compound of formula:
wherein
R 4 is CH 3 , Et, iPr, or n Bu;
R 10 is NH 2 , —NHR′, or —NR′ 2 ;
R 11 is H, —OH, or —NH 2 ; and
R′ is C 1-4 alkyl, or alternatively, in the instance of —NR′ 2 , each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms;
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 15 , wherein R 11 is —NH 2 .
17. The compound of claim 16 , wherein R 10 is —NHR′ or —NR′ 2 .
18. The compound of claim 17 , wherein R 10 is —NHR′.
19. The compound of claim 18 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, or t-butyl.
20. The compound of claim 18 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, or i-butyl.
21. The compound of claim 18 , wherein R′ is methyl.
22. A compound of formula:
wherein
R 4 is C 1-4 alkyl;
R 10 is H, NH 2 , —NHR′, or —NR′ 2 ;
R 11 is H, —OH, or —NH 2 ; and
R′ is C 1-4 alkyl, or alternatively, in the instance of —NR′ 2 , each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms;
or a pharmaceutically acceptable salt thereof.
23. The compound of claim 22 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, or t-butyl.
24. The compound of claim 22 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, or i-butyl.
25. The compound of claim 22 , wherein R′ is methyl.
26. The compound of claim 22 , wherein R 4 is CH 3 , Et, iPr, or n Bu.
27. The compound of claim 26 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, or t-butyl.
28. The compound of claim 26 , wherein R′ is methyl, ethyl, propyl, i-propyl, n-butyl, or i-butyl.
29. The compound of claim 26 , wherein R′ is methyl.