NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

摘要

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.

主权项

1. A compound of Formula (I): or a pharmaceutically acceptable salt thereof; wherein:
R1 is selected from (C1-C4 alkyl)-O, spirooxirane, cyano, ═O, nitro, (C1-C4 alkyl)C(O), and HO(C1-C4 alkyl)C(O);R2 is ═O, H, or ORa, where Ra is selected from H, optionally substituted C1-C4 alkyl, or optionally substituted aryl, with the proviso that when R2 is ═O, R5 is not present;R3 is H, optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl;R4 is independently selected from H and unsubstituted C1-C4 alkyl;R5 is substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;R6 is H, optionally substituted C1-C4 alkyl, or optionally substituted C1-C4 alkoxy;R7 is H, optionally substituted C1-C4 alkoxy, or an optionally substituted morpholinyl ring;R8, when present, is H or optionally substituted C1-C4 alkyl;- - - denotes an optional, additional C—C bond, resulting in either a C═C bond between C4-C5 or C5-C6, with the proviso that when present, the C5—H substituent is not present; and,- - - denotes an optional, additional C—C bond, resulting in a C═C bond between C16-C17, with the proviso that when present, the R1 is not ═O.