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 method of inducing 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:
or a pharmaceutically acceptable salt thereof to the subject.
2. 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 to the subject, said pharmaceutical composition comprising:
(a) a compound selected from the group consisting of a compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof; and
(b) a pharmaceutically acceptable carrier.
3. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
4. The method according to claim 3 , wherein the compound is a pharmaceutically acceptable salt of
5. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
6. The method according to claim 5 , wherein the compound is a pharmaceutically acceptable salt of
7. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
8. The method according to claim 7 , wherein the compound is a pharmaceutically acceptable salt of
9. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
10. The method according to claim 9 , wherein the compound is a pharmaceutically acceptable salt of
11. The method according to claim 9 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
12. The method according to claim 11 , wherein the compound is a pharmaceutically acceptable salt of
13. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
14. The method according to claim 13 , wherein the compound is a pharmaceutically acceptable salt of
15. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
16. The method according to claim 15 , wherein the compound is a pharmaceutically acceptable salt of
17. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
18. The method according to claim 17 , wherein the compound is a pharmaceutically acceptable salt of
19. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
20. The method according to claim 19 , wherein the compound is a pharmaceutically acceptable salt of
21. A method of inducing STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
22. The method according to claim 21 , wherein the compound is a pharmaceutically acceptable salt of