Cyclic di-nucleotide compounds as sting agonists

Patent metadata

Field	Value
Publication number	US-10106574-B2
Application number	US-201615234182-A
Country	US
Kind code	B2
Filing date	Aug 11, 2016
Priority date	Aug 13, 2015
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

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.

First claim

What is claimed is:

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

Assignees

• Merck Sharp & Dohme

Inventors

• Altman Michael D
• Chang Wonsuk
• Cumming Jared N
• Liang Rui
• Lim Jongwon
• Siu Tony
• Trotter Benjamin Wesley
• Truong Quang T
• Walsh Shawn P

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K31/7084

  Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide · CPC title

• C07H19/23

  Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22 · CPC title

• A61K31/7076

  containing purines, e.g. adenosine, adenylic acid · CPC title