Neuroactive steroids with perfluorobenzoyl group

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• 作者：Ivan ?erny ; Milo? Bud¨§?¨ªnsky ; Vladim¨ªr Pouzar ; Vojt¨§ch Vyklicky ; Barbora Krausov¨¢ ; Ladislav Vyklicky Jr.
• 关键词：Neuroactive steroids ; Synthesis ; Perfluorobenzoates ; NMDA receptor
• 刊名：Steroids
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：77
• 期：12
• 页码：1233-1241
• 全文大小：460 K

文摘

During an initial study in searching for the alternative derivatives suitable for photolabeling of neuroactive steroids, perfluorobenzoates and perfluorobenzamides in position 17 of 5¦Â-androstan-3¦Á-ol were synthesized from the corresponding 17-hydroxy and 17-amino derivatives. After transformation into glutamates or sulfates, 17¦Á-epimers had comparable inhibitory activity at NMDA receptors to the natural neurosteroid (20-oxo-5¦Â-pregnan-3¦Â-yl sulfate), however, were more potent (2- to 36-fold) than their 17¦Â-substituted analogs. In one case, fluorine in position 4¡ä of perfluorobenzoate group was substituted with azide and activity of the final glutamate was retained comparing with the corresponding perfluorobenzoate. The series was expanded with perfluorobenzoyl derivatives of pregnanolone: Perfluorobenzamide of glutamate and perfluorobenzoate of 11¦Á-hydroxy pregnanolone were prepared and tested. From nine tested compounds, four of them exhibit very good inhibition activity and can serve as promising leads for photolabeling experiments.