Substituted nucleosides, nucleotides and analogs thereof
Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.
1. A method for ameliorating or treating a Filoviridae viral infection comprising contacting a cell infected with a Filoviridae virus with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the structure:
wherein:
B 1A is
R 3A is OH;
R 4A is halogen;
R a1 and R a2 are independently hydrogen or deuterium;
R A is hydrogen or deuterium;
R 1A is hydrogen or;
R 2A is azido, halogen(C 1-6 alkyl) or —(CH 2 ) 1-6 N 3 ;
R 5A is hydrogen;
R 6A and R 7A are independently absent or hydrogen R 29A ; or
R 6A is
and R 7A is absent or hydrogen;
R 12A and R 13A are independently absent or hydrogen;
R 14A is O − or OH;
m is 0 or 1; and
Z 1A is O.
2. The method of claim 1 , wherein the Filoviridae virus is Ebolavirus.
3. The method of claim 1 , wherein the Filoviridae virus is Marburgvirus.
4. The method of claim 1 , wherein R 2A is halogen(C 1-6 alkyl).
5. The method of claim 1 , wherein R 2A is azido.
6. The method of claim 1 , wherein R 2A is —(CH 2 ) 1-6 N 3 .
7. The method of claim 1 , wherein R 4A is fluoro.
8. The method of claim 1 , wherein R 1A is hydrogen.
9. The method of claim 1 , wherein R 1A is
wherein R 6A and R 7A are independently absent or hydrogen.
10. The method of claim 1 , wherein R 6A is
wherein m is 0; and R 7A , R 12A and R 13A are independently absent or hydrogen.
11. The method of claim 1 , wherein R 6A is
wherein m is 1; R 7A , R 12A and R 13A are independently absent or hydrogen; and R 14A is O − or OH.
12. The method of claim 1 , wherein R 3A is OH.
13. The method of claim 1 , wherein R A is hydrogen.
14. The method of claim 1 , wherein R a1 and R a2 are both hydrogen.
15. The method of claim 1 , wherein B 1A is
16. The method of claim 1 , wherein B 1A is
17. The method of claim 1 , wherein the compound is selected from the group consisting of:
a pharmaceutically acceptable salt of the foregoing.
18. The method of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt of the foregoing.
19. The method of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt of the foregoing.
20. The method of claim 1 , further comprising the use of an interferon, ribavirin, (2S,3S,4R,5R)-2-(4-amino-5H-pyrrolo [3 ,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)pyrrolidine-3 ,4-diol, 5 -Fluoro-2-oxo-1H-pyrazine-3 -carboxamide, hexadecyloxypropyl-cidofovir, AVI-7537, AVI-7288, ZMapp or TKM-Ebola, or a pharmaceutically acceptable salt of the foregoing.
21. The method of claim 1 , wherein R 2A is —(CH 2 ) 1-6 F.
22. The method of claim 1 , wherein R 2A is fluoromethyl.
23. The method of claim 1 , wherein R 2A is azidomethyl.
24. The method of claim 1 , wherein B 1A is
25. The method of claim 17 , wherein B 1A is