- Stereoselective synthesis of the two major metabolites of spironolactone, 3α- and 3β-hydroxy-7α-methylthio-17α-pregn-4-ene-21,17-carbolactone
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7α-Methylthio-3β-hydroxy-17α-pregn-4-ene-21,17-carbolactone and 7α-methylthio-3α-hydroxy-17α-pregn-4-ene-21,17-carbolactone, the two major metabolites of spironolactone, were prepared stereoselectively by exploring different types of reduction reagents. For the 3β-hydroxyl isomer, the application of NaBH4/CeCl3·7H2O gave the best result while for the 3α-hydroxyl isomer, K-selectride seemed to provide the highest stereoselectivity.
- Li, Guo,Zhang, Yan
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Read Online
- EX VIVO METHODS FOR PREDICTING AND CONFIRMING IN VIVO METABOLISM OF PHARMACEUTICALLY ACTIVE COMPOUNDS
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Methods and compositions for the catalytic oxidation of pharmaceutically active compounds, and more particularly to ex vivo methods for predicting in vivo metabolism of pharmaceutically active compounds, including predicting in vivo interaction between two or more pharmaceutically active compounds.
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Page/Page column 36; 37; 38
(2015/06/25)
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- A safe and practical method for the preparation of 7α-Thioether and thioester derivatives of spironolactone
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Spironolactone is a renal competitive aldosterone antagonist. One of its most important metabolite is the 7α-methylthio spironolactone: thus it is very important to have an efficient and safe access to this compound, for pharmacokinetic studies. In this context, we synthesized this metabolite by thioalkylation of 7α-Thio spironolactone using Hu?nig's base with a very good yield. We also used our procedure to prepare, with an easy work-up and high yields, 7α-Thioether and thioester derivatives of spironolactone, that could be useful for further Structure-Activity Relationships studies.
- Agusti, Géraldine,Bourgeois, Sandrine,Cartiser, Nathalie,Fessi, Hatem,Le Borgne, Marc,Lomberget, Thierry
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p. 102 - 107
(2013/02/22)
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- Isolation and identification of novel sulfur-containing metabolites of spironolactone (Aldactone)
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In the urine of subjects given an oral dose of spironolactone [3-(3-oxo-7α-acetylthio-17β-hydroxy-4-androsten-17α-y1)propionic acid γ-lactone], six metabolites have been detected. One of the major metabolites was found to be the previously characterized de-thioacetylated compound, 3-(3-oxo-17β-hydroxy-4,6-androstadien-17α-y1)propionic acid γ-lactone (canrenone). Besides this a new major sulfur-containing metabolite has been isolated and identified as 3-(3-oxo-7α-methylsulfinyl-6β,17β-dihydroxy-4-androsten-17α-y1)propionic acid γ-lactone. This structural assignment was based on detailed analysis of its IR, NMR and UV spectra as well as comparison of its physical constants and chromatographic (TLC and GLC) characteristics with a synthetic sample. The three minor metabolites were found to be very labile and were readily converted to canrenone.
- Karim, Aziz,Brown, Edward A.
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