The invention relates to an efficient and industrially applicable process for the preparation and purification of allopregnanolone and intermediates thereof without the assistance of column chromatography.

The present invention contemplates novel neurosteroid derivative compounds, such as derivatives of ganaxolone and allopregnanolone, having improved solubility and bioavailability. The novel neurosteroid derivative compounds are characterized by the following formulas:

##STR00001## wherein R.sup.1 is methyl or hydrogen, R.sup.2 is an ester function (R—C(O)O—), R.sup.3 is hydrogen, R.sup.4 is alpha or beta hydrogen, R.sup.5 is R—CO— or any hydrocarbon structure (R—), and wherein R (in R.sup.2 or R.sup.5) is independently selected from any structure comprising 10 carbon atoms or fewer, which is linear or branched, saturated or unsaturated, may comprise cyclic or aromatic functions within the structure, and wherein R contains no more than 1 OH or NR.sub.2, or 2 ether or thioether functions.

Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein n, R.sup.19, R.sup.5, R.sup.3, R.sup.6a, R.sup.6b, R.sup.2a, R.sup.2b, R.sup.4a, R.sup.4b, R.sup.7a, R.sup.7b, R.sup.11, R.sup.12a, R.sup.12b, R.sup.16, R.sup.21a, R.sup.21b, and R.sup.21c 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##

The present invention generally relates to a specific pregnenolone derivative for its use for the treatment of a cognitive disorders. More particularly, the invention relates to a compound of Formula (I)

##STR00001##

for its use in the treatment of cognitive disorders. Indeed, the compound of the invention is in vivo very potent in correcting the cognitive impairments observed in cognitive disorders.

Steroid derivative regulators, a method for preparing the same, and uses thereof are described. Specifically, a compound as shown in formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and uses thereof as a regulator of GABA A receptor for treating depression, convulsion, Parkinson's disease, and nervous system diseases are described, wherein the substituents of the formula (I) are as defined in the description.

##STR00001##

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.

The present invention further provides method of preparing nanocrystals of a hydrophobic therapeutic gent such as fluticasone or triamcinolone, pharmaceutical compositions (e.g., topical or intranasal compositions) thereof and methods for treating and/or preventing the signs and/or symptoms of disorders such as blepharitis, Meibomian gland dysfuntion or skin inflammation or a respiratory disease (e.g., asthma).

Potent soft corticosteroid pharmaceutical compositions comprising them and method for use as anti-inflammatory agents. Also, a method for softening fluticasone propionate and similar corticosteroids to arrive at potent but safer alternatives. The compound 5-fluoromethyl 17α-dichloroacetoxy-6α,9α-difluoro-11β-hydroxy-16a-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, which is equally potent to but safer than fluticasone, is among those provided. Another compound of particular interest is 2-hydroxyethyl 17α-dichloroacetoxy-6α,9α-difluoro-11β-hydroxy-16β-methyl-3-oxoandrosta-1,4-diene-17β-carboxylate.

A crystal form X of 3α-hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1′-yl)-19-nor-5β-pregnan-20-one, a preparation method of said crystal form and an application thereof in preparing a drug for treatment of central nervous system disease.

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.