Neuroactive steroids and compositions thereof
Provided herein is a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein R 1a , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 5 , R 6a , R 6b , R 7a , R 7a , R 11a , R 11b , R 12a , R 12b , R 16a , R 16b , R 19 , R 11a , R 22 , R X , R Y and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.
1. A compound of Formula (I-e6):
or a pharmaceutically acceptable salt thereof;
wherein:
each of R 2a , R 2b , R 15a ,and R 15b is hydrogen;
R 3 is unsubstituted C 1-3 alkyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 ;
R 19 is hydrogen, methyl, or ethyl;
R X is —OH;
R Y is methyl; and
R 22 is —CN.
2. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 3 is methyl, ethyl, or propyl.
3. The compound or pharmaceutically acceptable salt of claim 2 , wherein R 3 is methyl.
4. The compound or pharmaceutically acceptable salt of claim 2 , wherein R 3 is ethyl.
5. The compound or pharmaceutically acceptable salt of claim 2 , wherein R 3 is propyl.
6. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 3 is —CH 2 OCH 3 .
7. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 3 is —CH 2 OCH 2 CH 3 .
8. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 19 is hydrogen.
9. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 19 is methyl.
10. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 19 is ethyl.
11. A compound selected from
Com-
pound
No.
Structure
2
3
7
11
15
24
26
or a pharmaceutically acceptable salt thereof.
12. A compound selected from
Com-
pound
No.
Structure
29
42
44
or a pharmaceutically acceptable salt thereof.
13. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 1 and a pharmaceutically acceptable excipient.
14. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 11 and a pharmaceutically acceptable excipient.
15. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 12 and a pharmaceutically acceptable excipient.
16. A compound of the formula
or a pharmaceutically acceptable salt thereof.
17. A compound of the formula
or a pharmaceutically acceptable salt thereof.
18. A compound of the formula
or a pharmaceutically acceptable salt thereof.
19. A compound of the formula
or a pharmaceutically acceptable salt thereof.
20. A compound of the formula
or a pharmaceutically acceptable salt thereof.
21. A compound of the formula
or a pharmaceutically acceptable salt thereof.
22. A compound of the formula
or a pharmaceutically acceptable salt thereof.
23. A compound of the formula
or a pharmaceutically acceptable salt thereof.
24. A compound of the formula
or a pharmaceutically acceptable salt thereof.
25. A compound of the formula
or a pharmaceutically acceptable salt thereof.