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.

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

##STR00001##

A process is provided for the making of estetrol starting from a 3-A-oxy-estra-1,3,5(10),15-tetraen-17-one, wherein A is an C.sub.1-C.sub.5 alkyl group, preferably a methyl group, or a C.sub.7-C.sub.12 benzylic group, preferably a benzyl group. This process is particularly suitable to industry.

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.3a, R.sup.3b, R.sup.4a, and R.sup.4b are as defined herein, and A is a carbon bound substituted or unsubstituted 5- to 6-membered heteroaryl ring 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.

A process for fluorination of aromatic compounds employing iodonium ylides and applicable to radiofluorination using .sup.18F is described. Processes, intermediates, reagents and radiolabelled compounds are described.

The invention relates to a process for producing a compound comprising an .sup.18F-difluoromethyl group or a compound comprising an .sup.18F-difluoromethylene group, which process comprises contacting a compound comprising a nucleophilic group with .sup.18F-difluorocarbene. The invention also relates to a compound of Formula (I). Compounds comprising an .sup.18F-difluoromethyl group or an .sup.18F-difluoromethylene group are also the subject of the present invention.

A process for the preparation of a compound of formula (IIa) is described where A is a silyl protecting group, in high diastereoisomeric purity and in crystalline form, comprising the crystallization of a mixture of the compound of formula (IIa) and its isomer of formula (IIb), where A is a silyl protecting group, from an ethereal solvent. The invention also provides a process for preparing Estetrol of formula (I) in high diastereoisomeric purity, comprising the use of the compound of formula (IIa), in a crystalline form, as a starting material.

##STR00001##

Methods of preparing fluorinated compounds by carboxylative fluorination using fluoride are contained herein. Fluorinated compounds are provided. Methods of using fluorinated compounds are contained herein.

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 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I): ##STR00001##
and pharmaceutically acceptable salts thereof; wherein , R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.5, R.sup.6, and R.sup.7 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.