Cyclic di-nucleotide compounds as sting agonists
A class of polycyclic compounds of general formula (I), of general formula (I′), or of general formula (I″), wherein Base 1 , Base 2 , Y, Y a , X a , X a1 , X b , X b1 , X c , X c1 , X d , X d1 , R 1 , R 1a , R 2 , R 2a , R 3 , R 4 , R 4a , R 5 , R 6 , R 6a , R 7 , R 7a , R 8 , and R 8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.
1. A compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
2. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
3. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
4. A pharmaceutical composition, said pharmaceutical composition comprising:
(a) a compound selected from the group consisting of a compound according to claim 1 , pharmaceutically acceptable salts thereof; and
(b) a pharmaceutically acceptable carrier.
5. A method of inducing an immune response in a subject, said method comprising administering a therapeutically effective amount of a compound selected from the group consisting of a compound according to claim 1 and pharmaceutically acceptable salts thereof to the subject.
6. A method of inducing an immune response in a subject, said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to claim 4 to the subject.
7. A method of inducing a STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound selected from the group consisting of a compound according to claim 1 and pharmaceutically acceptable salts thereof to the subject.
8. A method of inducing a STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to claim 4 to the subject.
9. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
10. The compound according to claim 9 wherein the compound is a pharmaceutically acceptable salt of
11. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
12. The compound according to claim 11 , wherein the compound is a pharmaceutically acceptable salt of
13. The compound according to claim 11 , wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
14. The compound according to claim 11 , wherein the compound is a pharmaceutically acceptable salt of
15. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
16. The compound according to claim 15 , wherein the compound is a pharmaceutically acceptable salt of
17. The compound according to claim 15 , wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
18. The compound according to claim 15 , wherein the compound is a pharmaceutically acceptable salt of
19. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
20. The compound according to claim 19 , wherein the compound is a pharmaceutically acceptable salt of
21. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
22. The compound according to claim 21 , wherein the compound is a pharmaceutically acceptable salt of
23. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
24. The compound according to claim 23 , wherein the compound is a pharmaceutically acceptable salt of
25. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
26. The compound according to claim 25 , wherein the compound is a pharmaceutically acceptable salt of
27. The compound according to claim 25 , wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
28. The compound according to claim 25 , wherein the compound is a pharmaceutically acceptable salt of
29. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
30. The compound according to claim 29 , wherein the compound is a pharmaceutically acceptable salt of
31. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
32. The compound according to claim 31 , wherein the compound is a pharmaceutically acceptable salt of
33. A compound, wherein the compound is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
34. The compound according to claim 33 , wherein the compound is a pharmaceutically acceptable salt of