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 method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of 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. A method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof.
3. A method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof.
4. A method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof.
5. A method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof.
6. A method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof.
7. A method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof.