Synthesis and GABA(A) receptor activity of 6-oxa-analogs of neurosteroids.
The 6-oxasteroids 3alpha-hydroxy-6-oxa-5alpha-pregnan-20-one (3) and 3alpha-hydroxy-6-oxa-5beta-pregnan-20-one (4) were obtained from pregnenolone acetate via the corresponding (5alpha or 5beta) 3beta, 20beta-diacetoxy-6-oxa-pregnane. Both steroids showed ca. 100-fold reduced potency for modulating [(3)H]flunitrazepam, [(3)H]muscimol or [(35)S]TBPS binding to the GABA(A) receptor when compared to their natural carbon analogs 3alpha-hydroxy-5alpha-pregnan-20-one (1) and 3alpha-hydroxy-5beta-pregnan-20-one (2).
Nicoletti
D
D
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de, Buenos Aires, Argentina.
Ghini
A A
AA
Furtmüller
R
R
Sieghart
W
W
Dodd
R H
RH
Burton
G
G
D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000494:pharmacology; D002778:Cholestanones / Q000138:chemical synthesis* / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism / Q000494:pharmacology; D018757:GABA Modulators / Q000737:chemistry / Q000494:pharmacology; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013256:Steroids / Q000737:chemistry*; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002778:Cholestanones; D018757:GABA Modulators; D011963:Receptors, GABA-A; D013256:Steroids; D009118:Muscimol; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate