4-azaindole compounds
Disclosed are compounds of Formula (I) N-oxides, or salts thereof, wherein G, A, R 1 , R 5 , and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.
1. A compound of Formula (I)
or a salt thereof, wherein:
G is
A is cyclohexyl substituted R 12a ;
R 1 is CH(CH 3 ) 2 ;
each R 2 is independently CH 3 or —OCH 3 ;
R 5 is F or —CH 3 ;
R 12a is:
p is 1 or 2; and
n is zero or 1.
2. The compound according to claim 1 or a salt thereof, wherein:
A is:
3. The compound according to claim 1 or a salt thereof, wherein:
G is
4. The compound according to claim 1 or a salt thereof, wherein:
A is:
and
G is
5. The compound according to claim 4 or a salt thereof, wherein:
R 12a is:
6. The compound according to claim 4 or a salt thereof, wherein:
R 12a is:
7. The compound according to claim 1 or a salt thereof, wherein said compound is selected from:
6-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (244);
6-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (248);
6-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (281, 288);
6-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (317, 319);
6-(4-(6-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (343-344);
6-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (435, 437);
6-((1r,4r)-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (438);
6-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-2-oxa-6-azaspiro[3.3]heptane (1037);
6-((1s,4s)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (1053);
6-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-1-oxa-6-azaspiro[3.3]heptane (1055);
6-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-1-oxa-6-azaspiro[3.3]heptane (1057);
7-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-2-oxa-7-azaspiro[4.4]nonane (1059);
6-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-2-oxa-6-azaspiro[3.4]octane (1060);
2-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-6-oxa-2-azaspiro[3.4]octane (1061);
6-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-2-oxa-6-azaspiro[3.4]octane (1063);
2-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-6-oxa-2-azaspiro[3.4]octane (1065);
7-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-2-oxa-7-azaspiro[4.4]nonane (1066);
6-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-2-oxa-6-azaspiro[3.4]octane (1068);
2-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-6-oxa-2-azaspiro[3.4]octane (1069);
2-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-6-oxa-2-azaspiro[3.4]octane (1070);
6-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-2-oxa-6-azaspiro[3.4]octane (1073);
6-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-1-oxa-6-azaspiro[3.3]heptane (1074);
6-[4-(2-{8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-1-oxa-6-azaspiro[3.3]heptane (1075);
6-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-1λ 6 -thia-6-azaspiro[3.3]heptane-1,1-dione (1076);
and 6-[4-(2-{7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-3-(propan-2-yl)-1H-pyrrolo[3,2-b] pyridin-5-yl)cyclohexyl]-1λ 6 -thia-6-azaspiro[3.3]heptane-1,1-dione (1077).
8. A compound having the structure:
or a salt thereof.
9. The compound according to claim 8 .
10. The compound according to claim 8 , wherein said compound is a salt.
11. A pharmaceutical composition comprising a compound according to claim 8 or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier.
12. A method of treating an autoimmune disease or a chronic inflammatory disease, comprising administering to a mammalian patent a compound according to claim 8 or a pharmaceutically-acceptable salt thereof, wherein said autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS), and Sjögren's syndrome.
13. A compound having the structure:
or a salt thereof.
14. The compound according to claim 13 .
15. The compound according to claim 13 , wherein said compound is a salt.
16. A pharmaceutical composition comprising a compound according to claim 13 or a pharmaceutically-acceptable salt thereof and a pharmaceutically acceptable carrier.
17. A method of treating an autoimmune disease or a chronic inflammatory disease, comprising administering to a mammalian patent a compound according to claim 13 or a pharmaceutically-acceptable salt thereof, wherein said autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS), and Sjögren's syndrome.
18. A compound having the structure:
or a salt thereof.
19. The compound according to claim 18 .
20. The compound according to claim 18 , wherein said compound is a salt.
21. A pharmaceutical composition comprising a compound according to claim 18 or a pharmaceutically-acceptable salt thereof and a pharmaceutically acceptable carrier.
22. A method of treating an autoimmune disease or a chronic inflammatory disease, comprising administering to a mammalian patent a compound according to claim 18 or a pharmaceutically-acceptable salt thereof, wherein said autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS), and Sjögren's syndrome.
23. The compound according to claim 1 or a salt thereof, wherein said compound is:
24. The compound according to claim 1 or a salt thereof, wherein said compound is:
25. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier.
26. A method for treating a disease comprising administrating to a subject in need thereof, a therapeutically-effective amount of at least one compound according to claim 1 or a pharmaceutically-acceptable salt thereof, wherein the disease is an autoimmune disease or a chronic inflammatory disease.
27. The method according to claim 26 or a pharmaceutically-acceptable salt thereof, wherein said autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS), and Sjögren's syndrome.