| Identification | Back Directory | [Name]
GANAXOLONE | [CAS]
38398-32-2 | [Synonyms]
3α-hydroxy-3β-methyl-5α-pregnan-20-one
(3α,5α)-3-Hydroxy-3-methyl-pregnan-20-one
1-((3R,5S,8R,9S,10S,13S,14S,17S)-3-Hydroxy-3,10,13-trimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethanone | [Molecular Formula]
C22H36O2 | [MDL Number]
MFCD00945298 | [MOL File]
38398-32-2.mol | [Molecular Weight]
332.52 |
| Chemical Properties | Back Directory | [Melting point ]
190-192° | [alpha ]
D +103° | [Boiling point ]
434.8±18.0 °C(Predicted) | [density ]
1.036±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: ~4.2 mg/mL
| [form ]
solid
| [pka]
15.18±0.70(Predicted) | [color ]
white
|
| Hazard Information | Back Directory | [Description]
Ganaxolone is a 3β-methylated synthetic analog of the neurosteroid allopregnanolone that allosterically enhances GABAA receptor current.1,2 At nanomolar concentrations, it can potentiate GABA-evoked currents at GABAA receptor complexes containing α1, α2, α3, β2, and γ2L subunits expressed in Xenopus oocytes.1,2 Ganaxolone has been shown to have a broad range of antiseizure activity in animal epilepsy models and human clinical trials.3,4,5 | [Uses]
Treatment of epilepsy and migraine. | [Application]
Ganaxolone (marketed as Ztalmy) is a first-in-class neuroactive steroid that acts as a positive modulator of gamma-aminobutyric acid (GABA) A receptors for the treatment of seizures associated with cyclooxygenase-dependent kinase-like 5 (CDKL5) deficiency (CDD). | [Definition]
ChEBI: Ganaxolone is a corticosteroid hormone. | [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. | [Mechanism of action]
Ganaxolone works by positively modulating GABAA receptors, the major inhibitory neurotransmitter receptors in the central nervous system. This modulatory effect helps reduce the frequency and severity of seizures associated with CDD. | [Synthesis]
The synthesis begins with protection of the keto functionality in the natural steroid pregnenolone 10.1. Using acid catalysis, reaction with boiling ethylene glycol in toluene forms the acetal 10.2 in 88% yield. Oxidation of 10.2 to form the ketone 10.3 has been accomplished by a variety of methods, including Swern, Dess-Martin, and TPAP conditions. The oxidation process depicted in Figure 3.1 demonstrates the formation of the ketone 10.3 using calcium hypochlorite and TEMPO. Next, methylation is accomplished by the addition of MeMgBr in the presence of lithium chloride and ferric chloride to afford the tertiary alcohol 10.4. Finally, removal of the acetal protecting group by treatment with iodine in dichloromethane and acetone affords ganaxolone 10 in 98% yield over the last two steps.
 | [storage]
+4°C |
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