Synthesis and GABAA Receptor Activity of Oxygen-Bridged Neurosteroid Analogues

ALVAREZ, L.D; VELEIRO, A.S.; BAGGIO, R.F.; GARLAND, M.T.; EDELSZTEIN, V.C.; COIRINI, H.; BURTON, G.

BIOORGANIC & MEDICINAL CHEMISTRY.

Elsevier

Año: 2008 vol. 16 p. 3831 - 3838

0968-0896

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 3a-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-[3H]butylbicycloorthobenzoate as radiolabeled ligand for the GABAA receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1a,11a-Epoxypregnanolone (6) was more active than pregnanolone (2).