Macrocyclic spiropyrrolidine derived antiviral agents
The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof: which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.
1. A compound represented by Formula (XIII-6A),
wherein
m is 4;
L is —CH 2 — or —O—;
each R 31 and R 32 is hydrogen;
R 1 is C 1 -C 8 -alkyl, arylalkyl or C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl; and
A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or —(CO)—NHR 2 , wherein R 2 is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl.
2. The compound of claim 1 , wherein the compound is
3. The compound of claim 1 , wherein the compound is
4. The compound of claim 1 , wherein the compound is
5. The compound of claim 1 , wherein the compound is
6. The compound of claim 1 , wherein the compound is
7. The compound of claim 1 , wherein the compound is
8. The compound of claim 1 , wherein the compound is
9. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or excipient.
10. A pharmaceutical composition comprising the compound of claim 2 and a pharmaceutically acceptable carrier or excipient.
11. A pharmaceutical composition comprising the compound of claim 3 and a pharmaceutically acceptable carrier or excipient.
12. A pharmaceutical composition comprising the compound of claim 4 and a pharmaceutically acceptable carrier or excipient.
13. A pharmaceutical composition comprising the compound of claim 5 and a pharmaceutically acceptable carrier or excipient.
14. A pharmaceutical composition comprising the compound of claim 6 and a pharmaceutically acceptable carrier or excipient.
15. A pharmaceutical composition comprising the compound of claim 7 and a pharmaceutically acceptable carrier or excipient.
16. A pharmaceutical composition comprising the compound of claim 8 and a pharmaceutically acceptable carrier or excipient.
17. A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .
18. A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 2 .
19. A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 3 .
20. A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 4 .
21. A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 5 .
22. A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 6 .
23. A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 7 .
24. A method of treating a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound claim 8 .