Bioorg Med Chem. 2008 Apr 1;16(7):3831-8. Epub 2008 Jan 30.

Synthesis and GABA(A) receptor activity of oxygen-bridged neurosteroid analogs.

Alvarez LD, Veleiro AS, Baggio RF, Garland MT, Edelsztein VC, Coirini H, Burton G.

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Departamento de Química Orgánica and UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.

Abstract

Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3alpha-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activity of the synthetic steroids was assayed in vitro using t-[(3)H]butylbicycloorthobenzoate as radiolabeled ligand for the GABA(A) receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1alpha,11alpha-Epoxypregnanolone (6) was more active than pregnanolone (2).

PMID:: 18262792; [PubMed - indexed for MEDLINE]

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