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

Bioorg Med Chem. 2008 Apr 1;16(7):3831-8. doi: 10.1016/j.bmc.2008.01.048. Epub 2008 Jan 30.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Male
  • Models, Molecular
  • Molecular Structure
  • Neurons / drug effects*
  • Oxygen / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism*
  • Steroids / chemical synthesis*
  • Steroids / chemistry
  • Steroids / pharmacology*

Substances

  • Receptors, GABA-A
  • Steroids
  • Oxygen