Nucleoside derivatives and methods of use thereof
Certain anti-viral compounds, pharmaceutical compositions, and methods related thereto are disclosed.
1. A compound of Formula IV, or a pharmaceutically acceptable salt thereof,
wherein R 1 or R 2 is independently H, —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, wherein the —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, is optionally substituted with one or more substituents each independently selected from the group consisting of halo and OH.
2. A compound of Formula V, or a pharmaceutically acceptable salt thereof,
wherein R 1 is independently H, —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, wherein the —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, is optionally substituted with one or more substituents each independently selected from the group consisting of halo.
3. A compound of Formula VI, or a pharmaceutically acceptable salt thereof,
wherein R 1 or R 2 is independently H, —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, wherein the —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, is optionally substituted with one or more substituents each independently selected from the group consisting of halo and OH.
4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, having the structure of Formula VII:
wherein R 1 is independently H, —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, wherein the —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, is optionally substituted with one or more substituents each independently selected from the group consisting of halo.
5. A compound of Formula VIII, or a pharmaceutically acceptable salt thereof,
wherein R1 or R2 is independently H, —(CO)C1-C6 alkyl, or —(CO)C5-C10 aryl, wherein the —(CO)C1-C6 alkyl, or —(CO)C5-C10 aryl, is optionally substituted with one or more substituents each independently selected from the group consisting of halo and OH.
6. A compound of Formula IX, or a pharmaceutically acceptable salt thereof,
wherein R1 is independently H, —(CO)C1-C6 alkyl, or —(CO)C5-C10 aryl, wherein the —(CO)C1-C6 alkyl, or —(CO)C5-C10 aryl, is optionally substituted with one or more substituents each independently selected from the group consisting of halo.
7. A compound of Formula X, or a pharmaceutically acceptable salt thereof,
wherein R1 or R2 is independently H, —(CO)C1-C6 alkyl, or —(CO)C5-C10 aryl, wherein the —(CO)C1-C6 alkyl, or —(CO)C5-C10 aryl, is optionally substituted with one or more substituents each independently selected from the group consisting of halo and OH.
8. A compound of Formula XI, or a pharmaceutically acceptable salt thereof,
wherein R 1 is independently H, —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, wherein the —(CO)C 1 -C 6 alkyl, or —(CO)C 5 -C 10 aryl, is optionally substituted with one or more substituents each independently selected from the group consisting of halo.
9. A compound of Formula I
or a pharmaceutically acceptable salt thereof,
wherein R 1 or R 2 is independently H, heteroaryl, —(CO)C 1 -C 6 alkyl, —(CO)OC 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, (CO)OC 5 -C 10 aryl, —(CO)OC 5 -C 10 heteroaryl, —(CO)NHC 1 -C 6 alkyl, (CO)NHC 5 -C 10 aryl, or (CO)NHC 5 -C 10 heteroaryl, wherein the heteroaryl, —(CO)C 1 -C 6 alkyl, —(CO)OC 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, —(CO)OC 5 -C 10 aryl, —(CO)OC 5 -C 10 heteroaryl, —(CO)NHC 1 -C 6 alkyl, (CO)NHC 5 -C 10 aryl or (CO)NHC 5 -C 10 heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halo, OH, —O—C 1 -C 6 alkyl, NR 6 R 5 , C 1 -C 6 alkyl, C 5 -C 10 aryl and heteroaryl,
wherein R 5 or R 6 is independently H, OH, C 1 -C 6 alkyl, —(CO)C 1 -C 6 alkyl, —(CO)OC 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, C 5 -C 10 aryl or C 5 -C 10 heteroaryl,
wherein the link is independently selected from the group consisting of
wherein each R 7 and R 8 is independently selected from H and C 1 -C 6 alkyl and wherein R 7 and R 8 can fuse to each other to form a ring, and,
wherein R 3 or R 4 is independently H, D, F, Cl, Br, CH 3 , or CF 3 .
10. A compound of Formula I
or a pharmaceutically acceptable salt thereof,
wherein R 1 or R 2 is independently H, heteroaryl, —(CO)C 1 -C 6 alkyl, —(CO)C 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, (CO)OC 5 -C 10 aryl, —(CO)OC 5 -C 10 heteroaryl, —(CO)NHC 1 -C 6 alkyl, (CO)NHC 5 -C 10 aryl, or (CO)NHC 5 -C 10 heteroaryl, wherein the heteroaryl, —(CO)C 1 -C 6 alkyl, —(CO)OC 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, —(CO)OC 5 -C 10 aryl, —(CO)OC 5 -C 10 heteroaryl, —(CO)NHC 1 -C 6 alkyl, (CO)NHC 5 -C 10 aryl or (CO)NHC 5 -C 10 heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halo, OH, —O—C 1 -C 6 alkyl, NR 6 R 5 , C 1 -C 6 alkyl, C 5 -C 10 aryl and heteroaryl,
wherein R 3 or R 4 is independently H, D, halo or C 1 -C 3 alkyl, wherein alkyl is optionally substituted with one or more halo,
wherein the link is independently selected from the group consisting of
wherein each R 7 and R 8 is independently selected from H and C 1 -C 6 alkyl and wherein R 7 and R 8 can fuse to each other to form a ring, and
wherein R 5 or R 6 is independently H, OH, C 1 -C 6 alkyl, —(CO)C 1 -C 6 alkyl, or —(CO)OC 1 -C 6 alkyl.
11. A pharmaceutical composition, comprising a pharmaceutically acceptable excipient and a compound of Formula I
or a pharmaceutically acceptable salt thereof,
wherein R 1 or R 2 is independently H, heteroaryl, —(CO)C 1 -C 6 alkyl, —(CO)C 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, (CO)OC 5 -C 10 aryl, —(CO)OC 5 -C 10 heteroaryl, —(CO)NHC 1 -C 6 alkyl, (CO)NHC 5 -C 10 aryl, or (CO)NHC 5 -C 10 heteroaryl, wherein the heteroaryl, —(CO)C 1 -C 6 alkyl, —(CO)OC 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, —(CO)OC 5 -C 10 aryl, —(CO)OC 5 -C 10 heteroaryl, —(CO)NHC 1 -C 6 alkyl, (CO)NHC 5 -C 10 aryl or (CO)NHC 5 -C 10 heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halo, OH, —O—C 1 -C 6 alkyl, NR 6 R 5 , C 1 -C 6 alkyl, C 5 -C 10 aryl and heteroaryl,
wherein R 3 or R 4 is independently H, D, halo or C 1 -C 3 alkyl, wherein alkyl is optionally substituted with one or more halo,
wherein R 5 or R 6 is independently H, OH, C 1 -C 6 alkyl, —(CO)C 1 -C 6 alkyl, —(CO)C 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, C 5 -C 10 aryl or C 5 -C 10 heteroaryl,
wherein the link is independently selected from the group consisting of
and
wherein each R 7 and R 8 is independently selected from H and C 1 -C 6 alkyl and wherein R 7 and R 8 can fuse to each other to form a ring.
12. A method of treating or preventing a virus infection in a patient, comprising;
administering to the patient an effective amount of a compound of Formula I
or a pharmaceutically acceptable salt thereof,
wherein R 1 or R 2 is independently H, heteroaryl, —(CO)C 1 -C 6 alkyl, —(CO)OC 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, (CO)OC 5 -C 10 aryl, —(CO)OC 5 -C 10 heteroaryl, —(CO)NHC 1 -C 6 alkyl, (CO)NHC 5 -C 10 aryl, or (CO)NHC 5 -C 10 heteroaryl, wherein the heteroaryl, —(CO)C 1 -C 6 alkyl, —(CO)OC 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, —(CO)OC 5 -C 10 aryl, —(CO)OC 5 -C 10 heteroaryl, —(CO)NHC 1 -C 6 alkyl, (CO)NHC 5 -C 10 aryl or (CO)NHC 5 -C 10 heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halo, OH, —O—C 1 -C 6 alkyl, NR 6 R 5 , C 1 -C 6 alkyl, C 5 -C 10 aryl and heteroaryl,
wherein R 3 or R 4 is independently H, D, halo or C 1 -C 3 alkyl, wherein alkyl is optionally substituted with one or more halo,
wherein R 5 or R 6 is independently H, OH, C 1 -C 6 alkyl, —(CO)C 1 -C 6 alkyl, —(CO)OC 1 -C 6 alkyl, —(CO)C 5 -C 10 aryl, —(CO)C 5 -C 10 heteroaryl, C 5 -C 10 aryl or C 5 -C 10 heteroaryl,
wherein the link is independently selected from the group consisting of
and
wherein each R 7 and R 8 is independently selected from H and C 1 -C 6 alkyl and wherein R 7 and R 8 can fuse to each other to form a ring.
13. The method of claim 12 , wherein the virus infection is COVID-19.
14. A pharmaceutical composition, comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:
15. A pharmaceutical composition, comprising a pharmaceutically acceptable excipient and a compound of claim 3 .
16. A method of treating or preventing a virus infection in a patient, comprising:
administering to the patient an effective amount of a compound of claim 3 .
17. The method of claim 16 , wherein the virus infection is COVID-19.
18. A pharmaceutical composition, comprising a pharmaceutically acceptable excipient and a compound of claim 4 .
19. A method of treating or preventing a virus infection in a patient, comprising:
administering to the patient an effective amount of a compound of claim 4 .
20. The method of claim 19 , wherein the virus infection is COVID-19.