کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1359204 | 981397 | 2009 | 8 صفحه PDF | دانلود رایگان |
The synthesis of new analogues of allopregnanolone with a bridged sulfamidate ring over the β-face of ring A has been achieved from easily available precursors, using an intramolecular aziridination strategy. The methodology also allows the synthesis of 3α-substituted analogues such as the 3α-fluoro derivative. GABAA receptor activity of the synthetic analogues was evaluated by assaying their effect on the binding of [3H]flunitrazepam and [3H]muscimol. The 3α-hydroxy-2,19-sulfamoyl analogue and its N-benzyl derivative were more active than allopregnanolone for stimulating binding of [3H]flunitrazepam. For the binding of [3H]muscimol, both synthetic analogues and allopregnanolone stimulated binding to a similar extent, with the N-benzyl derivative exhibiting a higher EC50. The 3α-fluoro derivative was inactive in both assays.
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Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 18, 15 September 2009, Pages 6526–6533