Methods and systems for making intermediates in the synthesis of onapristone are provided. Aspects include the photoconversion of onapristone synthesis intermediates using a narrow band frequency light source.

The present disclosure describes glucocorticoid agonist compounds, their conjugates with binding proteins, pharmaceutical compositions thereof, as well as methods and uses for treating diseases or conditions, such as autoimmune or inflammatory conditions.

The present invention relates to a new process for the synthesis of 3?-hydroxy-5?-pregnan-20-one, commonly known as brexanolone, wherein the corresponding cyclic 20-ketal or cyclic 20-thioketal compound of formula (IV) is deprotected with the use or iodine in an organic solvent: (I). ##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.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.

Described herein are neuroactive steroids of the Formula (II): or a pharmaceutically acceptable salt thereof; wherein A, R.sup.1, R.sup.2a, R.sup.2b, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.5, R.sup.6 and 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##

Compounds having the formula ##STR00001##
or solvates of the compounds can be used as intermediates in the preparation of the synthetic steroids, Etonogestrel and Desogestrel, as well as other pharmaceutically active agents.

Methods and systems for making intermediates in the synthesis of onapristone are provided. Aspects include the photoconversion of onapristone synthesis intermediates using a narrow band frequency light source.

The functionalized 3,4-alkylenedioxythiophene (ADOT+) monomers can be represented by a chemical formula (CR.sup.1R.sup.2)(CR.sup.3R.sup.4)(CR.sup.4R.sup.5).sub.xO.sub.2C.sub.4H.sub.2S, wherein x=0 or 1; wherein each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is independently selected from hydrogen, a hydrocarbyl moiety, and a heteroatom-containing functional group; and wherein at least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 comprises the heteroatom-containing functional group selected from an aldehyde, a maleimide, and their derivatives thereof. Also, disclosed herein are aldehyde derivatives represented by (ADOT-CH.sub.2NH).sub.pY and a maleimide derivative represented by (ADOT-(CH.sub.2).sub.qN).sub.pZ where p=1-2 and each of Y and Z is a hydrocarbyl moiety or a biofunctional hydrocarbyl moiety. In an embodiment of the ADOT+ monomers, one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is replaced by a direct bond to an amide group, an azide group, or an ester group of a biofunctional hydrocarbyl moiety. Also, disclosed herein are polymers and copolymers made therefrom.

The present disclosure provides processes for the synthesis of withanolides such as Withanolide A and Withanolide D.

Described herein are compositions and methods for the treatment or prevention of dermal or ocular surface disorders. Ocular surface disorders include ocular allergy, dry eye disease, ocular manifestation of graft versus host disease and other inflammatory and/or infectious diseases of the (e.g., anterior) surface of the eye(s). Said compositions and methods comprise keratolytic conjugates which demonstrate immunological, keratolytic, anti-inflammatory, and/or other desirable activities. Topical administration of said compositions to the eyelid margin or surrounding areas provides therapeutic benefit to patients suffering from ocular surface disorders.