Substituted pyrido[2,1-a]isoquinolines as VMAT2 inhibitors
This disclosure relates generally to VMAT2 inhibitor compounds of Formula (Ia): and pharmaceutically acceptable salts thereof, as well as compositions and methods related thereto.
1. A compound of Formula (Ia):
or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is:
2. The compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical product comprising at least one pharmaceutically acceptable excipient and a compound according to claim 1 , or a pharmaceutically acceptable salt thereof;
wherein the pharmaceutical product is selected from the group consisting of a kit, a pharmaceutical composition, a pharmaceutical formulation, and a pharmaceutical unit dosage form.
7. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the compound according to claim 2 , or a pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the compound according to claim 3 , or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the compound according to claim 4 , or a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the compound according to claim 5 , or a pharmaceutically acceptable salt thereof.
12. A method for treating a neurological disease, a neurological disorder, a psychiatric disease, or a psychiatric disorder in a subject in need thereof, wherein the method comprises administering to the subject a compound according to claim 1 , or a pharmaceutically acceptable salt thereof;
wherein the neurological disease, neurological disorder, psychiatric disease, or psychiatric disorder is selected from the group consisting of:
an agitation associated with Alzheimer's disease, an agitation associated with fragile X syndrome, an agitation associated with fragile X-associated tremor-ataxia syndrome, an autism spectrum disorder, chorea-acanthocytosis, a hyperkinetic movement disorder, a mood disorder, a neurological dysfunction associated with Lesch-Nyhan syndrome, Rett syndrome, schizoaffective disorder, schizophrenia, and treatment-refractory obsessive-compulsive disorder.
13. The method according to claim 12 , wherein the neurological disease, neurological disorder, psychiatric disease, or psychiatric disorder is an autism spectrum disorder.
14. The method according to claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
15. The method according to claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
16. The method according to claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
17. The method according to claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
18. The method according to claim 12 , wherein the neurological disease, neurological disorder, psychiatric disease, or psychiatric disorder is a hyperkinetic movement disorder.
19. The method according to claim 18 , wherein the hyperkinetic movement disorder is tardive dyskinesia.
20. The method according to claim 19 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
21. The method according to claim 19 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
22. The method according to claim 19 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
23. The method according to claim 19 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
24. The method according to claim 12 , wherein the neurological disease, neurological disorder, psychiatric disease, or psychiatric disorder is treatment-refractory obsessive-compulsive disorder.
25. The method according to claim 24 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
26. The method according to claim 24 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
27. The method according to claim 24 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
28. The method according to claim 24 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.