Anti-viral nucleoside analogs and methods for treating viral infections, especially HIV infections
The present invention relates to novel compounds according to the general formulas I, II, III, IV or V: wherein B is nucleoside base according to the structure: and the remaining variables as defined in the specification, and pharmaceutical compositions comprising the compounds. The compounds are useful interalia as anti-viral agents in viral therapy.
1. A compound according to the formula:
Wherein B is
R is H, F, Cl, Br, I or C 1 -C 4 alkyl, —C≡C—R a ,
X is H or F;
R 2 is H, a C 2 -C 21 acyl group, a phosphate, a diphosphate, a triphosphate or a phosphodiester group;
R 3 is a —(CH 2 ) n —C≡C—R a group;
R 3a and R 3b are each independently H or F;
R a is H or a —C 1 -C 4 alkyl;
n is 0.1 or 2;
or an anomer or pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 wherein R is C 1 -C 3 alkyl,
and X is H.
3. The compound according to claim 1 wherein R is CH 3 , R 3 is —(CH 2 ) n —C≡C—R a , n is 0 or 1 and R a is H or CH 3 .
4. The compound according to claim 3 wherein R 3a and R 3b are both H.
5. The compound according to claim 4 wherein R 2 is H or ea a C 2 -C 21 acyl group.
6. The compound according to claim 1 which is
7. The compound according to claim 6 wherein R 2 is H, a C 2 -C 21 acyl group, a phosphate group, disphosphate group or a triphosphate group, or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 7 wherein R 2 is H, a C 2 -C 21 acyl group, a phosphate or diphosphate group, or a pharmaceutically acceptable salt form.
9. The compound according to claim 6 wherein R 2 is H, a C 2 -C 21 acyl group or a phosphate, or a pharmaceutically acceptable salt or anomer thereof.
10. The compound according to claim 9 wherein R 2 is H or a C 2 -C 21 acyl group.
11. A compound according to the chemical structure:
Wherein R 2 is H or a C 2 -C 11 acyl group.
12. A pharmaceutical composition comprising an effective amount of a compound for use in the treatment of a viral disease state, disorder or a condition associated with a viral disease state according to the chemical structure:
Wherein B is
R is H, F, Cl, Br, I, C 1 -C 4 alkyl, —C≡C—R a ,
X is H or F;
R 2 is H, a C 2 -C 21 acyl group, a phosphate group, a diphosphate group, a triphosphate group or a phosphodiester group;
R 3 is a —(CH 2 ) n —C≡C—R a group;
R 3a and R 3b are each independently H or F;
R a is H or a —C 1 -C 4 alkyl;
n is 0, 1 or 2;
or an anomer or pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier, additive or excipient.
13. The composition according to claim 12 wherein R is C 1 -C 3 alkyl,
and X is H.
14. The composition according to claim 12 wherein R is CH 3 , R 3 is —(CH 2 ) n —C≡C—R a , n is 0 or 1 and R a is H.
15. The composition according to claim 14 wherein R 3a and R 3b are both H.
16. The composition according to claim 15 wherein R 2 is H or a C 2 -C 21 acyl group.
17. The composition according to claim 12 wherein said compound is
18. The composition according to claim 17 wherein R 2 is H, a C 2 -C 21 acyl group, a phosphate, diphosphate or triphosphate group, or a pharmaceutically acceptable salt thereof.
19. The composition according to claim 17 wherein R 2 is H, a C 2 -C 21 acyl group, a phosphate or diphosphate group, or a pharmaceutically acceptable salt form thereof.
20. The composition according to claim 17 wherein R 2 is H, a C 2 -C 21 acyl group or a phosphate group, or a pharmaceutically acceptable salt thereof.
21. The composition according to claim 20 wherein R 2 is H or a C 2 -C 21 acyl group.
22. A pharmaceutical composition comprising an effective amount of a compound according to claim 11 for use in the treatment of a viral disease state, disorder or a condition associated with a viral disease state in combination with a pharmaceutically acceptable carrier, additive or excipient.