Allopregnanolone and Pregnanolone Analogues Modified in the C Ring: Synthesis and Activity

0392261 - ÚOCHB 2014 RIV US eng J - Journal Article
Slavíková, Barbora - Bujons, J. - Matyáš, Libor - Vidal, M. - Babot, Z. - Krištofíková, Z. - Suňol, C. - Kasal, Alexander
Allopregnanolone and Pregnanolone Analogues Modified in the C Ring: Synthesis and Activity.
Journal of Medicinal Chemistry. Roč. 56, č. 6 (2013), s. 2323-2336. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA ČR(CZ) GAP303/12/1464
Institutional support: RVO:61388963
Keywords : steroids * synthesis of neurosteroid analogues * GABAA receptor * [3H]flunitrazepam binding * intact neurons in culture * 3D-QSAR analysis
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 5.480, year: 2013

25R-3 beta-Hydroxy-5 alpha-spirostan-12-one (hecogenin) and 11 alpha-hydroxypregn-4-ene-3,20-dione (11 alpha-hydroxyprogesterone) were used as starting materials for the synthesis of a series of 11- and 12-substituted derivatives of 5 xi-pregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one), the principal neurosteroid acting via gamma-aminobutyric acid (GABA). These analogues were designed to study the structural requirements of the corresponding GABA(A) receptor. Their biological activity was measured by in vitro test with [H-3]flunitrazepam as radio-ligand in which allopregnanolone and its active analogues stimulated the binding to the GABA(A) receptor. Analysis of the SAR data suggests dependence of the flunitrazepam binding activity on the hydrophobic-hydrophilic balance of the groups at the C-ring edge rather than on specific interactions between them and the receptor.
Permanent Link: http://hdl.handle.net/11104/0221183