Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogues

ALVAREZ, LAUTARO D.; VELEIRO, ADRIANA S.; BAGGIO, RICARDO F.; GARLAND, MARÍA T.; EDELSZTEIN, VALERIA C.; COIRINI, HÉCTOR; BURTON, GERARDO

BIOORGANIC & MEDICINAL CHEMISTRY.

Elsevier

Año: 2008 vol. 16 p. 3831 - 3838

0968-0896

Three analogues 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 radiolabelled 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)