Neuroactive steroids with perfluorobenzoyl group

作者：Cerny Ivan^*; Budesinsky Milos; Pouzar Vladimir; Vyklicky Vojtech; Krausova Barbora; Vyklicky Ladislav Jr

来源：Steroids, 2012, 77(12): 1233-1241.

DOI：10.1016/j.steroids.2012.07.004

• Neuroactive steroids
• Synthesis
• Perfluorobenzoates
• NMDA receptor

During an initial study in searching for the alternative derivatives suitable for photolabeling of neuroactive steroids, perfluorobenzoates and perfluorobenzamides in position 17 of 5 beta-androstan-3 alpha-ol were synthesized from the corresponding 17-hydroxy and 17-amino derivatives. After transformation into glutamates or sulfates, 17 alpha-epimers had comparable inhibitory activity at NMDA receptors to the natural neurosteroid (20-oxo-5 beta-pregnan-3 beta-yl sulfate), however, were more potent (2- to 36-fold) than their 17 beta-substituted analogs. In one case, fluorine in position 4%26apos; 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 alpha-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.

• 出版日期2012-10