Synthesis and GABA(A) receptor activity of 2,19-sulfamoyl analogues of allopregnanolone.

Fernando J Durán Valeria C Edelsztein Alberto A Ghini Mariana Rey Héctor Coirini Philippe Dauban 1 Robert H Dodd 1 Gerardo Burton
1 ICSN - Institut de Chimie des Substances Naturelles
Abstract : The synthesis of new analogues of allopregnanolone with a bridged sulfamidate ring over the beta-face of ring A has been achieved from easily available precursors, using an intramolecular aziridination strategy. The methodology also allows the synthesis of 3alpha-substituted analogues such as the 3alpha-fluoro derivative. GABA(A) receptor activity of the synthetic analogues was evaluated by assaying their effect on the binding of [(3)H]flunitrazepam and [(3)H]muscimol. The 3alpha-hydroxy-2,19-sulfamoyl analogue and its N-benzyl derivative were more active than allopregnanolone for stimulating binding of [(3)H]flunitrazepam. For the binding of [(3)H]muscimol, both synthetic analogues and allopregnanolone stimulated binding to a similar extent, with the N-benzyl derivative exhibiting a higher EC(50). The 3alpha-fluoro derivative was inactive in both assays.
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https://hal.archives-ouvertes.fr/hal-00433251
Contributeur : Jocelyne Brunet <>
Soumis le : mercredi 18 novembre 2009 - 15:34:48
Dernière modification le : vendredi 15 novembre 2019 - 17:16:05

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Fernando J Durán, Valeria C Edelsztein, Alberto A Ghini, Mariana Rey, Héctor Coirini, et al.. Synthesis and GABA(A) receptor activity of 2,19-sulfamoyl analogues of allopregnanolone.. Bioorganic and Medicinal Chemistry, Elsevier, 2009, 17 (18), pp.6526-33. ⟨10.1016/j.bmc.2009.08.008⟩. ⟨hal-00433251⟩

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