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 are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I):

##STR00001##

and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, status epilepticus.

Compounds are provided according to Formula (I):

##STR00001##

and pharmaceutically acceptable salts thereof, wherein Z is a group of the formula (i), (ii), (iii), (iv), or (v):

##STR00002##

and wherein L.sup.1, L.sup.2, L.sup.3, X.sup.1, X.sup.2, Y, R.sup.Z4, R.sup.Z5, R.sup.Z6, n, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.6a, R.sup.6b, R.sup.7a, R.sup.7b, R.sup.11a, R.sup.11b, R.sup.14, R.sup.17, R.sup.19, R.sup.20, R.sup.23a, R.sup.23b, and R.sup.24 are as defined herein, and pharmaceutical compositions thereof. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of CNS-related conditions in mammals.

Described herein are steroids of Formula (I):

##STR00001##

and pharmaceutically acceptable salts thereof; wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.3, R.sup.4, R.sup.5a, R.sup.5b, R.sup.6 and Z are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

Provided herein are compounds of Formula (I-I): and pharmaceutically acceptable alts thereof; wherein p, R.sup.1, R.sup.3a, R.sup.2a, R.sup.11a, R.sup.11b, R.sup.6a, and R.sup.6b are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I-X) 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##

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I):

##STR00001##

and pharmaceutically acceptable salts thereof; wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined herein, and A is a heteroaryl ring system comprising 3 or 4 nitrogens as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I):

##STR00001##

and pharmaceutically acceptable salts thereof; wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are as defined herein, and A is a heteroaryl ring system comprising 3 or 4 nitrogens as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds.

##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.