Referenced in: none

Automatically associated channels: Kir2.3

Title: Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids.

Authors: María V Dansey, Pablo H Di Chenna, Adriana S Veleiro, Zdena Kristofíková, Hana Chodounska, Alexander Kasal, Gerardo Burton

Journal, date & volume: Eur J Med Chem, 2010 Jul , 45, 3063-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20417993

Abstract
A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3alpha-Hydroxy and 4alpha-hydroxy-A-homo-5-pregnen-20-one, analogues of the neuroactive steroid allopregnanolone, were obtained by means of a regioselective epoxidation of a double bond in the expanded A-ring, using a fructose-derived chiral ketone as catalyst and oxone as oxidant. Although both these compounds were marginally active in inhibiting TBPS binding to GABA(A) receptors, 3beta-hydroxy-A-homo-5-pregnen-20-one was almost as active as allopregnanolone. Reduction of the double bond of the latter compound resulted in a ten fold loss of activity.