(1-azinone)-substituted pyridoindoles
View Patent ↗Substituted pyridoindoles for incorporation in pharmaceutical compositions employed in the treatment of various diseases correspond to formula (I) wherein R 1 is H or optionally substituted alkyl; R 2 , R 3 , R 4 are each independently selected from H, —O-alkyl, —S-alkyl, alkyl, halo, —CF 3 , and —CN; G is —CR 12 R 13 —NR 5 — or —NR 5 —CR 12 R 13 ; R 5 is H, optionally substituted alkyl, optionally substituted heterocycle, —C(═O)—R 6 , —C(═O)—O—R 7 , or —C(═O)—NR 19 R 20 ; R 6 and R 7 are each optionally substituted alkyl or optionally substituted heterocycle; R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 19 and R 20 are each independently selected from H or optionally substituted alkyl; R 14 and R 15 are each independently H or halogen; L is —CH 2 —O—, —CH 2 CH 2 —, —CH═CH— or a bond; and B is aryl or heteroaryl or cycloalkyl; with the proviso that, when L is a direct bond, B cannot be unsubstituted heteroaryl or heteroaryl monosubstituted with fluorine.
1. A compound of formula I:
wherein
R 1 is H or optionally substituted alkyl;
R 2 , R 3 , R 4 are each independently selected from H, —O-alkyl, —S-alkyl, alkyl, halo, —CF 3 , and —CN;
G is —CR 12 R 13 —NR 5 — or —NR 5 —CR 12 R 13 ;
R 5 is H, optionally substituted alkyl;
R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 are each independently selected from H or optionally substituted alkyl;
Y is CH;
L is —CH 2 —O—; and
B is heteroaryl.
2. A compound according to claim 1 wherein G is —CH 2 —NR 5 —.
3. A compound according to claim 1 wherein G is —NR 5 —CH 2 —.
4. A compound according to claim 1 wherein R 5 is H.
5. A compound according to claim 1 wherein R 5 is optionally substituted alkyl.
6. A compound according to claim 5 wherein R 5 is selected from methyl, ethyl, 2-propyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl and 2-oxo-2-(pyrrolidin-1-yl)ethyl, 2-(pyrrolidin-1-yl)ethyl and (S)-pyrrolidin-2-ylmethyl.
7. A compound according to claim 1 wherein R 1 is H.
8. A compound according to claim 1 wherein R 1 is alkyl.
9. A compound according to claim 8 wherein R 1 is selected from methyl and ethyl.
10. A compound according to claim 1 wherein L is —CH 2 —O—.
11. A compound according to claim 1 wherein B is heteroaryl.
12. A compound according to claim 11 wherein B is pyridinyl.
13. A compound according to claim 12 wherein B is pyridin-2-yl.
14. A compound according to claim 12 wherein B is pyridin-3-yl.
15. A compound according to claim 11 wherein B is pyridazinyl.
16. A compound according to claim 15 wherein B is pyridazin-3-yl.
17. A compound according to claim 11 wherein B is pyrimidinyl.
18. A compound according to claim 17 wherein B is pyrimidin-5-yl.
19. A compound according to claim 17 wherein B is pyrimidin-2-yl.
20. A compound according to claim 1 wherein B, together with R 2 , R 3 and R 4 , is selected from pyridin-2-yl, 5-chloropyridin-2-yl, 5-(trifluoromethyl)pyridin-2-yl, 5-fluoropyridin-2-yl, 6-(trifluoromethyl)pyridazin-3-yl, 6-methylpyridazin-3-yl, 6-(trifluoromethyl)pyridin-3-yl, 2-(trifluoromethyl)pyrimidin-5-yl, 5-(trifluoromethyl)pyrimidin-2-yl, 5-methylpyridin-2-yl, 6-methylpyridin-3-yl, pyrimidin-2-yl, imidazo[1,2-α]pyridin-6-yl, imidazo[1,2-α]pyridin-2-yl.
21. A compound according to claim 1 wherein the compound is selected from,
22. A compound according to claim 1 wherein at least one of R 8 and R 9 is H.
23. A compound according to claim 1 wherein at least one of R 8 and R 9 is alkyl.
24. A compound according to claim 23 wherein at least one of R 8 and R 9 is methyl.
25. A compound according to claim 1 wherein R 10 is alkyl.
26. A compound according to claim 25 wherein R 10 is methyl.
27. A compound according to claim 1 wherein R 11 is alkyl.
28. A compound according to claim 27 wherein R 11 is methyl.
29. A compound according to claim 1 wherein R 12 is alkyl.
30. A compound according to claim 29 wherein R 12 is methyl.
31. A compound according to claim 1 wherein R 13 is alkyl.
32. A compound according to claim 31 wherein R 13 is methyl.
33. A compound according to claim 1 wherein R 10 , R 11 , R 12 and R 13 are each methyl.
34. A compound according to claim 1 wherein
G is —CH 2 —NR 5 — or —NR 5 —CH 2 —;
R 1 and R 5 are each independently H or methyl;
B is heteroaryl; and when L is —CH 2 —O—; then R 2 , R 3 , R 4 are each independently selected from H, —O-alkyl, —S-alkyl, alkyl, halo, —CF 3 , and —CN.
35. A compound according to claim 1 wherein the compound is in a pharmaceutically acceptable salt form.
36. A compound according to claim 35 wherein the salt is an HCl salt.
37. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, excipient or diluent therefore.
38. A method of treating obesity, comprising administering to a patient in need of obesity reduction an obesity-reducing effective amount of a compound according to claim 1 .
39. A method of treating anxiety, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound according to claim 1 .
40. A method of treating depression, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound according to claim 1 .
41. A method of treating non-alcoholic fatty liver disease, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound according to claim 1 .