COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS
Provided herein is a compound of Formula (1-I): or a pharmaceutically acceptable salt thereof, wherein R 2a , R 2b , R 3 , R 4a , R 4b , R 5 , R 6a , R 6b , R 11a , R 11b , R 16a , R 16b , R 19 , R 18 , X, q, r, s, t, u, and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (1-I) and methods of using the compounds, e.g. in the treatment of CNS-related disorders.
1 - 54 . (canceled)
55 . A compound of Formula (1-III-a), (1-III-b), (1-III-c), or (1-III-d):
or a pharmaceutically acceptable salt thereof,
wherein:
is a single or double bond, provided if a double bond is present, then R 5 and one of R 6a or R 6b are absent;
each n is independently 1 or 2;
each X is independently hydrogen, halogen, or 5-6 membered monocyclic heteroaryl having 2-4 nitrogen atoms, wherein the heteroaryl is optionally substituted with one group selected from halo, C 1-3 alkyl, —CN, or C 1-3 alkoxy;
R 5 is hydrogen or methyl, or when is a double bond, R 5 is absent;
R 19 is hydrogen, methyl, ethyl, or unsubstituted cyclopropyl;
R 18 is methyl or ethyl;
R 3 is C 1-3 alkyl optionally substituted with C 1-3 alkoxy; and
each of R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 11a , R 11b , R 16a , and R 16b is hydrogen.
56 . The compound or pharmaceutically acceptable salt of 55, wherein is a single bond.
57 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 5 is hydrogen or methyl in the cis position relative to the R 19 group.
58 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 5 is hydrogen or methyl in the trans position relative to the R 19 group.
59 . The compound or pharmaceutically acceptable salt of claim 55 , wherein is a double bond, and R 5 and one of R 6a or R 6b is absent.
60 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 18 is methyl.
61 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 18 is ethyl.
62 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 19 is hydrogen, methyl, or ethyl.
63 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 19 is hydrogen.
64 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 19 is ethyl.
65 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 19 is cyclopropyl.
66 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 3 is unsubstituted C 1-3 alkyl.
67 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 3 is methyl optionally substituted with C 1-3 alkoxy.
68 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 3 is selected from methyl, ethyl, propyl, methoxymethyl, or ethoxymethyl.
69 . The compound or pharmaceutically acceptable salt of claim 55 , wherein n is 1, and X is hydrogen.
70 . The compound or pharmaceutically acceptable salt of claim 55 , wherein n is 2, and X is hydrogen.
71 . The compound or pharmaceutically acceptable salt of claim 55 , wherein n is 1, and X is a 5-6 membered monocyclic heteroaryl having 2-4 nitrogen atoms, wherein the heteroaryl is optionally substituted with one group selected from halo, C 1-3 alkyl, —CN, or C 1-3 alkoxy.
72 . The compound or pharmaceutically acceptable salt of claim 71 , wherein X is
73 . The compound or pharmaceutically acceptable salt of claim 72 , wherein X is
74 . A compound selected from the group consisting of:
Example
STRUCTURE
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
85
86
87
88
89
90
91
and
92
or a pharmaceutically acceptable salt thereof.
75 . The compound or pharmaceutically acceptable salt of claim 74 , wherein the compound or pharmaceutically acceptable salt is a compound selected from the group consisting of:
Example
STRUCTURE
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
and
35
or a pharmaceutically acceptable salt thereof.
76 . The compound or pharmaceutically acceptable salt of claim 74 , wherein the compound or pharmaceutically acceptable salt is a compound selected from the group consisting of:
Example
STRUCTURE
85
86
87
88
89
90
91
and
92
or a pharmaceutically acceptable salt thereof.
77 . The compound or pharmaceutically acceptable salt of claim 74 , wherein the compound or pharmaceutically acceptable salt is a compound selected from the group consisting of:
Example
STRUCTURE
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
85
86
87
88
89
90
91
and
92
78 . A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt of claim 55 and a pharmaceutically acceptable excipient.
79 . A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 74 and a pharmaceutically acceptable excipient.
80 . A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of the compound or pharmaceutically acceptable salt of claim 55 .