Science and Technology Production
Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids
Article
Authorship:
DANSEY, MARIA VIRGINIA ; Di Chenna, Pablo Hector ; Veleiro, Adriana S. ; Kritofíková, Z ; Chodounska, H. ; Kasal, A. ; Burton, GerardoDate:
2010Publishing House and Editing Place:
ElsevierMagazine:
EUROPEAN JOURNAL OF MEDICAL CHEMISTRY, vol. 45 (pp. 3063-3069) ElsevierSummary *
A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3á-Hydroxy and 4á-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, 3â-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. Information provided by the agent in SIGEVAKey Words
A-homopregnanegAminobutyric acidNeurosteroidGABAA receptor