Synthesis and GABA A receptor activity of 6-oxa-analogs of neurosteroids

The 6-oxasteroids 3α-hydroxy-6-oxa-5α-pregnan-20-one ( 3) and 3α-hydroxy-6-oxa-5β-pregnan-20-one ( 4) were obtained from pregnenolone acetate via the corresponding (5α or 5β) 3β,20β-diacetoxy-6-oxa-pregnane. Both steroids showed ca. 100-fold reduced potency for modulating [ 3H]flunitrazepam, [ 3H]mu...

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Veröffentlicht in:	Steroids 2000-06, Vol.65 (6), p.349-356
Hauptverfasser:	Nicoletti, Daniel, Ghini, Alberto A, Furtmüller, Roman, Sieghart, Werner, Dodd, Robert H, Burton, Gerardo
Format:	Artikel
Sprache:	eng
Schlagworte:	6-Oxapregnanolone 6-Oxasteroids Animals Antipsychotic Agents - chemistry Antipsychotic Agents - pharmacology Binding Sites Bridged Bicyclo Compounds, Heterocyclic - metabolism Bridged Bicyclo Compounds, Heterocyclic - pharmacology Cholestanones - chemical synthesis Cholestanones - pharmacology Flunitrazepam - metabolism Flunitrazepam - pharmacology GABA GABA A receptor GABA Modulators - chemistry GABA Modulators - pharmacology Hydrogen Bonding Inhibitory Concentration 50 Molecular Structure Muscimol - metabolism Muscimol - pharmacology Neurosteroids Rats Receptors, GABA-A - drug effects Receptors, GABA-A - metabolism Steroid Steroids - chemistry Structure-Activity Relationship
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Zusammenfassung:	The 6-oxasteroids 3α-hydroxy-6-oxa-5α-pregnan-20-one ( 3) and 3α-hydroxy-6-oxa-5β-pregnan-20-one ( 4) were obtained from pregnenolone acetate via the corresponding (5α or 5β) 3β,20β-diacetoxy-6-oxa-pregnane. Both steroids showed ca. 100-fold reduced potency for modulating [ 3H]flunitrazepam, [ 3H]muscimol or [ 35S]TBPS binding to the GABA A receptor when compared to their natural carbon analogs 3α-hydroxy-5α-pregnan-20-one ( 1) and 3α-hydroxy-5β-pregnan-20-one ( 2).
ISSN:	0039-128X 1878-5867
DOI:	10.1016/S0039-128X(00)00088-X