Neuroactive 19-alkoxy-17-substituted steroids, prodrugs thereof, and methods of treatment using same
The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.
1. A compound of Formula (I-g):
or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is selected from (C 1 -C 4 alkyl)-O, spirooxirane, cyano, ═O, nitro, (C 1 -C 4 alkyl)C(O), and HO(C 1 -C 4 alkyl)C(O);
R 2 is ═O, H, or OR a , where R a is selected from H, optionally substituted C 1 -C 4 alkyl, or optionally substituted aryl, with the proviso that when R 2 is ═O, R 8 is not present;
R 3 is H, optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, optionally substituted C 2 -C 4 alkynyl, or optionally substituted aryl;
R b is methyl;
R 8 , when present, is H or optionally substituted C 1 -C 4 alkyl;
- - - denotes an optional, additional C—C bond, resulting in a C═C bond between C 16 -C 17 , with the proviso that when present, the R 1 is not ═O or spirooxirane.
2. The compound of claim 1 , wherein the R 3 group is selected from the group consisting of H, methyl, and trifluoromethyl.
3. The compound of claim 1 , wherein R 2 is ═O, methoxy or H.
4. The compound of claim 1 , wherein R 1 is beta-cyano.
5. The compound of claim 1 selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
6. The compound of claim 1 , wherein
R 1 is selected from (C 1 -C 4 alkyl)-O, spirooxirane, cyano, ═O, (C 1 -C 4 alkyl)C(O), and HO(C 1 -C 4 alkyl)C(O).
7. A compound of the formula:
or a pharmaceutically acceptable salt thereof.
8. A compound of the formula:
or a pharmaceutically acceptable salt thereof.
9. A compound of the formula:
or a pharmaceutically acceptable salt thereof.
10. A compound of the formula:
or a pharmaceutically acceptable salt thereof.
11. A compound of the formula:
or a pharmaceutically acceptable salt thereof.
12. A compound of the formula:
or a pharmaceutically acceptable salt thereof.
13. A pharmaceutical composition comprising a compound of formula:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
14. A pharmaceutical composition comprising a compound of formula:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
15. A pharmaceutical composition comprising a compound of formula:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
16. A pharmaceutical composition comprising a compound of formula:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
17. A pharmaceutical composition comprising a compound of formula:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
18. A pharmaceutical composition comprising a compound of formula:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.