title: Neuroactive steroids with perfluorobenzoyl group.
abstract: During an initial study in searching for the alternative derivatives suitable for photolabeling of neuroactive steroids, perfluorobenzoates and perfluorobenzamides in position 17 of 5β-androstan-3α-ol were synthesized from the corresponding 17-hydroxy and 17-amino derivatives. After transformation into glutamates or sulfates, 17α-epimers had comparable inhibitory activity at NMDA receptors to the natural neurosteroid (20-oxo-5β-pregnan-3β-yl sulfate), however, were more potent (2- to 36-fold) than their 17β-substituted analogs. In one case, fluorine in position 4' 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 11α-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.
authors: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., 166 10 Prague 6, Czech Republic. cerny@uochb.cas.cz
authors: Ivan
authors: I
authors: Cerný
authors: Miloš
authors: M
authors: Buděšínský
authors: Vladimír
authors: V
authors: Pouzar
authors: Vojtěch
authors: V
authors: Vyklický
authors: Barbora
authors: B
authors: Krausová
authors: Ladislav
authors: L
authors: Vyklický
mesh_terms: D001386:Azides / Q000737:chemistry; D005466:Fluorocarbons / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D011278:Pregnanes / Q000737:chemistry; D011280:Pregnanolone / Q000737:chemistry; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001386:Azides; D005466:Fluorocarbons; D011278:Pregnanes; D016194:Receptors, N-Methyl-D-Aspartate; D013256:Steroids; D018698:Glutamic Acid; D011280:Pregnanolone