23930-19-0

Basic information

• Product Name: ALFAXALONE
• Synonyms: 3ALPHA-HYDROXY-5ALPHA-PREGNANE-11,20-DIONE;3-HYDROXY-5ALPHA-PREGNANE-11,20-DIONE;5ALPHA-PREGNAN-3ALPHA-OL-11,20-DIONE;ALFAXALONE;ALPHAXALONE;(3-alpha,5-alpha)-3-hydroxypregnane-11,20-dione;20-dione,3-alpha-hydroxy-5-alpha-pregnane-1;20-dione,3-hydroxy-,(3-alpha,5-alpha)-pregnane-1
• CAS NO: 23930-19-0
• Molecular Formula: C₂₁H₃₂O₃
• Molecular Weight: 332.48
• Mol File: 23930-19-0.mol

Chemical Properties

• Melting Point: 172-174°
• Boiling Point: 409.59°C (rough estimate)
• Flash Point: 251 °C
• Appearance: white/powder
• Density: 1.0834 (rough estimate)
• Vapor Pressure: 9.95E-11mmHg at 25°C
• Refractive Index: 1.5192 (estimate)
• Storage Temp.: Store at RT
• Solubility: chloroform: ≥5 mg/mL, clear, colorless
• PKA: 15.05±0.70(Predicted)
• CAS DataBase Reference: ALFAXALONE(CAS DataBase Reference)
• NIST Chemistry Reference: ALFAXALONE(23930-19-0)
• EPA Substance Registry System: ALFAXALONE(23930-19-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 22-36
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: TU4157800
• Hazardous Substances Data: 23930-19-0(Hazardous Substances Data)

Usage

Originator

Althesin ,Glaxo ,UK ,1972

Uses

Anesthetic;nociception blocker

Manufacturing Process

A solution of 3α-hydroxy-5α-pregn-16-ene-11,20-dione (200 mg) in freshly distilled tetrahydrofuran (8 ml) with 5% palladium on carbon (100 ml) was hydrogenated until hydrogen uptake ceased. The mixture was filtered through a pad of kieselguhr and the tetrahydrofuran removed in vacuum to give 196 mg, MP 171°C to 172°C.

Therapeutic Function

Anesthetic component

Biological Activity

A neurosteroid anesthetic that directly activates and potentiates GABA A receptor-activated membrane current (I GABA ). Efficacy but not potency is determined by the alpha subunit of the receptor (EC 50 values are 1.4, 1.8, 2.1, 2.4 and 2.5 μ M for α 1 β 1 γ 3, α 1 β 1 γ 1, β 1 γ 1, α 2 β 1 γ 2L and α 1 β 1 γ 2L isoforms respectively).

InChI:InChI=1/C21H32O3/c1-12(22)16-6-7-17-15-5-4-13-10-14(23)8-9-20(13,2)19(15)18(24)11-21(16,17)3/h13-17,19,23H,4-11H2,1-3H3/t13-,14+,15-,16+,17-,19+,20-,21+/m0/s1

Upstream product

• 2089-06-7 5α-pregnane-3,11,20-trione 
• 516-15-4 11-Ketoprogesterone 
• 5009-82-5 3β-acetoxy-5α,9β-pregnane-11,20-dione 
• 3684-81-9 3β-acetoxy-5α-pregnane-11,20-dione 
• 2265-09-0 3β-acetoxy-17-bromo-16β-fluoro-5α-pregnane-11,20-dione 
• 23738-34-3 (3S,20S)-20-formyl-5α-pregn-7-en-3-yl-acetate 
• 14646-73-2 3β-acetoxy-5α-pregn-7-en-20-one 
• 118490-28-1 3β-acetoxy-5α-pregna-7,9(11)-dien-20-one 
• 911653-74-2 3β-acetoxy-5α,9β-pregn-7-ene-11,20-dione 
• 115484-60-1 (20Ξ)-3β,21-diacetoxy-23,24-dinor-5α-chola-7,20-diene 
• 1053-19-6 3β-acetoxy-20β_F-hydroxy-5α,9β-pregnan-11-one 
• 1449-60-1 5-dihydroergosteryl acetate 
• 113926-54-8 3β-acetoxy-9,11α-epoxy-5α-pregn-7-en-20-one 
• 2724-68-7 3β-acetoxy-5α-pregn-16-ene-11,20-dione 

Downstream Products

• 570-39-8 (3β,5α)-3,17-dihydroxypregnane-11,20-dione 
• 989-80-0 3β-(toluene-4-sulfonyloxy)-5α-pregnane-11,20-dione 
• 20703-79-1 21-bromo-3β,17-dihydroxy-5α-pregnane-11,20-dione 
• 23930-29-2 5α-pregnan-3α,11β-diol-20-one 
• 38540-45-3 (3R,5S,8S,9S,10S,13S,14S,17S)-10,13-Dimethyl-3-nitrooxy-11-oxo-hexadecahydro-cyclopenta[a]phenanthrene-17-carboxylic acid phenyl ester 
• 38540-44-2 (3R,5S,8S,9S,10S,13S,14S,17S)-10,13-Dimethyl-3-nitrooxy-11-oxo-hexadecahydro-cyclopenta[a]phenanthrene-17-carboxylic acid 3,5-dihydroxy-phenyl ester 
• 38540-29-3 (3R,5S,8S,9S,10S,13S,14S,17S)-10,13-Dimethyl-3-nitrooxy-11-oxo-hexadecahydro-cyclopenta[a]phenanthrene-17-carboxylic acid 2-dibenzylamino-ethyl ester 
• 38540-31-7 (3R,5S,8S,9S,10S,13S,14S,17S)-10,13-Dimethyl-3-nitrooxy-11-oxo-hexadecahydro-cyclopenta[a]phenanthrene-17-carboxylic acid 2-[(4-ethoxy-phenyl)-ethyl-amino]-ethyl ester 
• 167947-08-2 (3β,5α)-21-(acetyloxy)-3-{[(4-methylphenyl)sulfonyl]oxy}pregnane-11,20-dione 
• 2089-06-7 5α-pregnane-3,11,20-trione 

Relevant articles and documents

NEUROACTIVE STEROIDS AND METHODS OF PREPARATION

Disclosed are neuroactive steroid anaesthetic agents, methods for their preparation and compositions comprising the same. The invention provides scaled up and/or GMP methods for preparing neuroactive steroids, such as alfaxalone, alfadolone and alfadolone acetate.

Allopregnanolone and pregnanolone analogues modified in the C ring: Synthesis and activity

(25R)-3β-Hydroxy-5α-spirostan-12-one (hecogenin) and 11α-hydroxypregn-4-ene-3,20-dione (11α-hydroxyprogesterone) were used as starting materials for the synthesis of a series of 11- and 12-substituted derivatives of 5ξ-pregnanolone (3α-hydroxy-5α- pregnan-20-one and 3α-hydroxy-5β-pregnan-20-one), the principal neurosteroid acting via γ-aminobutyric acid (GABA). These analogues were designed to study the structural requirements of the corresponding GABA A receptor. Their biological activity was measured by in vitro test with [3H]flunitrazepam as radioligand in which allopregnanolone and its active analogues stimulated the binding to the GABAA receptor. Analysis of the SAR data suggests dependence of the flunitrazepam binding activity on the hydrophobic-hydrophilic balance of the groups at the C-ring edge rather than on specific interactions between them and the receptor.

First synthesis of a C-homosteroid from pregn-4-ene-3,11,20-trione

(3α,5α)-3-Hydroxy-C-homopregnane-11,20-dione (3) was prepared in eleven steps from the commercially available pregn-4-ene-3,11,20-trione (4) via the 11-oxo-13-formyl-12,13-secopregnane intermediate 11 (Scheme 2). Subjection of this secopregnane to an intramolecular aldol condensation afforded the α,β-unsaturated key intermediate C-homopregn-12-en-11-one 12. Copyright