N-methyl-d-aspartate receptors (NMDAR) and/or potentiating y-aminobutyric acid receptors (GABAAR) agents and uses thereof are described. Uses of these agents include methods of treating or preventing various psychiatric diseases, disorders, or conditions and methods of treating or preventing alcohol use disorder in a subject in need thereof.

The present disclosure relates to stereodefined polycyclic (e.g., tetracyclic) compounds that contain quaternary centers at one or multiple ring fusions, synthetic methods for preparing such compounds, and methods of using such compounds to treat a disease, such as a brain tumor and, particularly, a glioma.

Provided herein is a compound of Formula (I) or pharmaceutically acceptable salt thereof, wherein R.sup.2a, R.sup.2b, R.sup.4a, R.sup.4b, R.sup.6, R.sup.7, R.sup.11a, R.sup.11b, R.sup.16, R.sup.17, R.sup.3, R.sup.5, R.sup.19 and R.sup.X are defined herein and wherein R.sup.Y represents optionally substituted heteroaryl. 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.

##STR00001##

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein -------, R.sup.1, R.sup.2, R.sup.5, A and L are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia. ##STR00001##

The present disclosure provides modified neuroactive steroids. The modified neuroactive steroids may comprise, consist of, or consist essentially of a therapeutic agent and/or a modifying moiety. The modified neuroactive steroid can have modified characteristics as compared to native neuroactive steroids that do not include a modifying moiety and/or therapeutic agent. The modified neuroactive steroid may be, for example, modified pregnenolone, pregnenolone metabolites, allopregnanolone, and/or allopregnanolone metabolites. The modified neuroactive steroids can be used to treat, prevent and/or ameliorating a phenotypic state of interest in a subject.

The present invention relates to compounds which are intermediates in the synthesis of bile acid derivatives with pharmacological activity. The invention relates to compounds of general formula (I): ##STR00001##
wherein: , R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease. In addition, the invention relates to a method of synthesizing these intermediates and a method of preparing obeticholic acid and obeticholic acid analogues from the compounds of the invention.

Provided herein is a compound of Formula (1-I): or a pharmaceutically acceptable salt thereof, wherein R.sup.2a, R.sup.2b, R.sup.3, R.sup.4a, R.sup.4b, R.sup.5, R.sup.6a, R.sup.6b, R.sup.11a, R.sup.11b, R.sup.16a, R.sup.16b, R.sup.19, R.sup.18, X, q, r, s, t, u, and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (1-I) and methods of using the compounds, e.g, in the treatment of CNS-related disorders.

##STR00001##

Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein n, R.sup.19, R.sup.5, R.sup.3a, R.sup.6a, R.sup.6b, R.sup.1, R.sup.2a, R.sup.2b, R.sup.4a, R.sup.4b, R.sup.7a, R.sup.7b, R.sup.11a, R.sup.11b, R.sup.12a, R.sup.12b, R.sup.17b, R.sup.15a, R.sup.15b, R.sup.16a and R.sup.16b 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. ##STR00001##

Described herein are neuroactive steroids of the Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof, wherein , A, R.sup.1, R.sup.2, R.sup.3a, R.sup.4a, R.sup.4b, R.sup.5, R.sup.7a, and R.sup.7b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

Provided herein is a compound of Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof, wherein R.sup.1a, R.sup.1b, R.sup.2a, R.sup.2b, R.sup.3, R.sup.4a, R.sup.4b, R.sup.5, R.sup.6a, R.sup.6b, R.sup.7a, R.sup.7a, R.sup.11a, R.sup.11b, R.sup.12a, R.sup.12b, R.sup.16a, R.sup.16b, R.sup.19, R.sup.11a, R.sup.22, R.sup.X, R.sup.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.