Neuroactive substituted cyclopent[
The present disclosure is generally directed to neuroactive substituted cyclopent[a]anthracenes 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):
or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is H,
R 2 is H,
R 3 is H, ═O, ═CHCN, ═CHCO 2 R t , where R t is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituded C 2 -C 4 alkynyl, —CN, β-OH, β-OR s , where R s is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl, β-NO 2 , spiroepoxy, or C(O)R r , where R r is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl;
R 4 is methyl;
R 5 is H,
R 6 is H,
R 7 is H,
R 8 is H,
R 9 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 10 is H,
R 11 is H or C(O)R e , where R e is optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl, or optionally substituted C 2 -C 20 alkynyl; and,
- - - denotes an optional double bond with the proviso that when present R 3 is not ═O, ═CHCN or ═CHCO 2 R t .
2. The compound of claim 1 , wherein R 11 is H.
3. The compound of claim 1 , wherein R 3 is ═O.
4. The compound of claim 1 , wherein R 3 is spiroepoxy.
5. The compound of claim 1 , wherein R 3 is β-CN.
6. The compound of claim 1 , wherein a double bond is present between C 2 -C 3 .
7. The compound of claim 6 , wherein R 3 is —CN.
8. The compound of claim 1 , having the structure (I-a):
wherein R 3 is ═O, ═CHCN, ═CHCO 2 R t , where R t is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl, —CN, β-OH, β-OR s , where R s is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl, β-NO 2 , spiroepoxy, or C(O)R r , where R r is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl; and,
- - - denotes an optional double bond, with the proviso that when present, R 3 is not ═O, ═CHCN or ═CHCO 2 R t .
9. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
13. A pharmaceutical composition comprising the compound of claim 1 , a pharmaceutically acceptable salt thereof, or a combination of two or more thereof, and a pharmaceutically acceptable carrier.
14. A method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.