38398-32-2

Usage

Uses

Used in Pharmaceutical Industry:
Ganaxolone is used as an antiseizure agent for the treatment of epilepsy and migraine. It acts as a potent and selective positive allosteric modulator of GABAA receptors, enhancing GABA-evoked currents at GABAA receptor complexes containing α1, α2, α3, β2, and γ2L subunits expressed in Xenopus oocytes. This modulation helps in reducing seizure activity and managing the symptoms of epilepsy and migraine.

Biological Activity

Potent positive allosteric modulator of GABA A receptors. Enhances GABA-evoked chloride currents in Xenopus oocytes expressing GABA A receptors (EC 50 values are 94, 122 and 213 nM for α 2 β 1 γ 2 L , α 3 β 1 γ 2 L and α 1 β 1 γ 2 L receptors respectively). Exerts anticonvulsive effects in a broad range of animal seizure models.

Biochem/physiol Actions

Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnane-20-one) is a positive allosteric modulator of the GABAA receptor subtype; synthetic analog of the endogenous neurosteroid allopregnanolone; effective against chemically induced seizures in rats and mice. Ganaxolone is an orally active analog of allopregnanolone that is not converted to the hormonally active 3-keto form. The enhanced anticonvulsant potency of ganaxolone after neurosteroid withdrawal supports the use of ganaxolone as a specific treatment for perimenstrual catamenial epilepsy.

InChI:InChI=1/C22H36O2/c1-14(23)17-7-8-18-16-6-5-15-13-20(2,24)11-12-21(15,3)19(16)9-10-22(17,18)4/h15-19,24H,5-13H2,1-4H3/t15-,16-,17+,18-,19-,20+,21-,22+/m0/s1

Upstream product

• 566-65-4 dihydroprogesterone 
• 145-13-1 Pregnenolone 
• 516-55-2 isopregnanolone 
• 75-16-1 methylmagnesium bromide 
• 75-24-1 trimethylaluminum 
• 917-54-4 methyllithium 
• 676-58-4 methylmagnesium chloride 
• 148256-45-5 1-((2’R,8R,10S,13S,14S,17S)-10,13-dimethylhexadecahydrospiro[cyclopenta[a]phenanthrene-3,2’-oxiran]-17-yl)ethanone 
• 55571-86-3 20,20-ethylenedioxy-3β-methyl-5α-pregnan-3α-ol 
• 162882-87-3 1-((3R,5S,8R,9S,10S,13S,14S,17S)-3-Hydroxy-3-iodomethyl-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-ethanone 

Relevant academic research and scientific papers

NEUROSTEROID COMPOUNDS AND METHODS FOR THEIR PREPARATION AND USE IN TREATING CENTRAL NERVOUS SYSTEM DISORDERS

Described herein is the chemical structure of neurosteroid derivative compounds, methods of synthesizing the derivatives, and their uses in treating disorders, including those of the central nervous system. These compounds are readily synthesized and have improved pharmaceutical properties, including water solubility, compared to known neurosteroids.

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein (II), A, R1, R2, R3a, R4a, R4b, R5, R7a, and R7b 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.

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Described herein are deuterium-enriched neuroactive steroids of the Formula (II) or a pharmaceutically acceptable salt thereof; wherein R2a, R2b, R3, R4a, R4b, R5, R6a, R6b

METHOD FOR MAKING 3α-HYDROXY, 3β- METHYL-5α-PREGNAN-20-ONE (GANAXOLONE)

Applicants have discovered a method for the stereoselective and regioselective synthesis of 3α-hydroxy, 3β-methyl-5α- pregnan-20-one (ganaxolone) comprising reacting 5α-pregnane-3,20-dione; with an organometallic methylating agent in an inert solvent to provide a compound of the formula.

Use of neurosteroids to treat neuropathic pain

Ganaxolone (3α-hydroxy-3β-methyl-5β-pregnan-20-one) and 3α-hydroxy-3β-methyl-5β-pregnan-20-one and their physiologically cleavable esters are useful for treating neuropathic pain. Compositions comprising a pharmaceutically acceptable excipient and an appropriate compound, along with methods for preparing the compositions are disclosed. Also disclosed are articles of manufacture wherein the composition is combine with labeling instructions for treating neuropathic pain.

Synthesis and in vitro activity of 3β-substituted-3α-hydroxypregnan- 20-ones: Allosteric modulators of the GABA(A) receptor

Two naturally occurring metabolites of progesterone, 3α-hydroxy-5α- and 5β-pregnan-20-one (1 and 2), are potent allosteric modulators of the GABA(A) receptor. Their therapeutic potential as anxiolytics, anticonvulsants, and sedative/hypnotics is limited b

Method for making 3α-hydroxy, 3β-substituted-pregnanes

This invention provides a simplified method for converting pregnan-3,20-dione compounds to 3α-hydroxy,3β-substituted-pregnanes. By selective use of reagents the unprotected dione is converted chemoselectively and diastereoselectively into a 3(R)-pregnan-3-spiro-2'oxirane-20-one intermediate. This intermediate can then be converted regioselectively by a second set of reactions to the 3α-hydroxy,3β-substituted-20-one form, which can be further modified at the 20-keto position. Through this method, each ketone group is independently treated. By modifying the ketones one at a time, one can obtain the desired stereo-specificity at each site.

METHODS, COMPOSITIONS, AND COMPOUNDS FOR ALLOSTERIC MODULATION OF THE GABA RECEPTOR BY MEMBERS OF THE ANDROSTANE AND PREGNANE SERIES

Method, compositions, and compounds for modulating brain excitability to alleviate stress, anxiety, insomnia and seizure activity using certain steroid derivatives that act at a newly identified site on the gamma-aminobutyric acid receptor-chloride ionophore (GR) complex.