SUBSTITUTED PYRIDO[2,1-a]ISOQUINOLINES AS VMAT2 INHIBITORS
This disclosure relates generally to VMAT 2 inhibitor compounds of Formula (Ia): and pharmaceutically acceptable salts thereof, as well as compositions and methods related thereto.
1 . A compound of Formula (Ia):
wherein:
R 1 is:
2 - 4 . (canceled)
5 . The compound according to claim 1 , wherein the compound is;
6 . (canceled)
7 . The compound according to claim 1 , wherein the compound is:
8 - 9 . (canceled)
10 . The compound according to claim 1 , wherein the compound is:
11 . (canceled)
12 . The compound according to claim 1 , wherein the compound is:
13 - 14 . (canceled)
15 . A pharmaceutical product comprising at least one pharmaceutically acceptable excipient and a compound according to claim 1 ;
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.
16 . A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a compound according to claim 1 .
17 - 19 . (canceled)
20 . 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 ;
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, 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.
21 - 29 . (canceled)
30 . A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the compound according to claim 5 .
31 . A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the compound according to claim 7 .
32 . A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the compound according to claim 10 .
33 . A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the compound according to claim 12 .
34 . The method according to claim 20 , wherein the neurological disease, neurological disorder, psychiatric disease, or psychiatric disorder is a hyperkinetic movement disorder.
35 . The method according to claim 34 , wherein the hyperkinetic movement disorder is tardive dyskinesia.
36 . The method according to claim 35 , wherein the compound is:
37 . The method according to claim 35 , wherein the compound is:
38 . The method according to claim 35 , wherein the compound is:
39 . The method according to claim 35 wherein the compound is:
40 . The method according to claim 20 , wherein the neurological disease, neurological disorder, psychiatric disease, or psychiatric disorder is treatment-refractory obsessive-compulsive disorder.
41 . The method according to claim 40 , wherein the compound is:
42 . The method according to claim 40 , wherein the compound is:
43 . The method according to claim 40 , wherein the compound is:
44 . The method according to claim 40 , wherein the compound is:
45 . The method according to claim 20 , wherein the neurological disease, neurological disorder, psychiatric disease, or psychiatric disorder is an autism spectrum disorder.
46 . The method according to claim 45 , wherein the compound is:
47 . The method according to claim 45 , wherein the compound is:
48 . The method according to claim 45 , wherein the compound is:
49 . The method according to claim 45 , wherein the compound is:
50 . The method according to claim 20 , wherein the neurological disease, the neurological disorder, the psychiatric disease, or the psychiatric disorder is schizophrenia.
51 . The method according to claim 50 , wherein the compound is:
52 . The method according to claim 50 , wherein the compound is:
53 . The method according to claim 50 , wherein the compound is:
54 . The method according to claim 50 , wherein the compound is:
55 . The method according to claim 50 , wherein the method comprises using the compound in adjunctive therapy.
56 . The method according to claim 55 , wherein the compound is:
57 . The method according to claim 55 , wherein the compound is:
58 . The method according to claim 55 , wherein the compound is:
59 . The method according to claim 55 , wherein the compound is:
60 . The method according to claim 20 , wherein the neurological disease, the neurological disorder, the psychiatric disease, or the psychiatric disorder is schizoaffective disorder.
61 . The method according to claim 60 , wherein the compound is:
62 . The method according to claim 60 , wherein the compound is:
63 . The method according to claim 60 , wherein the compound is:
64 . The method according to claim 60 , wherein the compound is:
65 . The method according to claim 60 , wherein the method comprises using the compound in adjunctive therapy.
66 . The method according to claim 65 , wherein the compound is:
67 . The method according to claim 65 , wherein the compound is:
68 . The method according to claim 65 , wherein the compound is:
69 . The method according to claim 65 , wherein the compound is:
70 . The method according to claim 20 , wherein the neurological disease, the neurological disorder, the psychiatric disease, or the psychiatric disorder is chorea.
71 . The method according to claim 70 , wherein the chorea is chorea associated with Huntington's disease.
72 . The method according to claim 71 , wherein the compound is:
73 . The method according to claim 71 , wherein the compound is:
74 . The method according to claim 71 , wherein the compound is:
75 . The method according to claim 71 , wherein the compound is:
76 . The method according to claim 71 , wherein the method comprises using the compound in adjunctive therapy.
77 . The method according to claim 76 , wherein the compound is:
78 . The method according to claim 76 , wherein the compound is:
79 . The method according to claim 76 , wherein the compound is:
80 . The method according to claim 76 , wherein the compound is: