A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone

@article{Agusti2013ASA,
  title={A safe and practical method for the preparation of 7$\alpha$-thioether and thioester derivatives of spironolactone},
  author={G. Agusti and S. Bourgeois and N. Cartiser and H. Fessi and M. B. Borgne and Thierry Lomberget},
  journal={Steroids},
  year={2013},
  volume={78},
  pages={102-107}
}
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 Hünig'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… Expand

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References

SHOWING 1-10 OF 22 REFERENCES
Isolation and identification of novel sulfur-containing metabolites of spironolactone (Aldactone).
TLDR
The three minor metabolites were found to be very labile and were readily converted to canrenone, and a new major sulfur-containing metabolite has been isolated and identified as 3-oxo-7 α -methylsulfinyl-6 β ,17 β -dihydroxy-4-androsten-17 α -y1)propionic acid γ -lactone. Expand
Identification of spironolactone metabolites in plasma and target organs of guinea pigs.
TLDR
Data suggest that TM is principally responsible for the renal antimineralocorticoid effects of SL and support the purported role of TH in the degradation of testicular cytochrome P-450. Expand
Simultaneous determination of spironolactone and its metabolites in human plasma.
TLDR
The precision and accuracy of the method were confirmed by relative standard deviations below 10% for different concentrations, except for the concentration equal to the quantitation limit, where these parameters ranged from 12-15%. Expand
Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain.
A series of thiol-based inhibitors containing a benzyl moiety at the P1' position have been synthesized and tested for their abilities to inhibit glutamate carboxypeptidase II (GCP II).Expand
Spironolactone-related inhibitors of type II 17beta-hydroxysteroid dehydrogenase: chemical synthesis, receptor binding affinities, and proliferative/antiproliferative activities.
TLDR
It was found that a para-substituted benzylthio group at the 7alpha-position enhances the inhibitory potency of spironolactone derivatives on type II 17beta-HSD, and offer an interesting tool to study the regulation of this enzyme in several biological systems. Expand
Spironolactone Metabolism: Steady‐State Serum Levels of the Sulfur‐Containing Metabolites
TLDR
It was concluded that unmetabolized spironolactone is present in the serum and that the sulfur‐containing metabolite IV rather than canrenone is the major metabolite in serum following single or repeated doses of spironlactone. Expand
Selective oxidation of spirolactone-related sulfides to corresponding sulfoxides and sulfones by hydrogen peroxide in the presence of N-hydroxysuccinimde
Spirolactone-related sulfides were oxidized to corresponding sulfoxides and sulfones selectively and in high yield by hydrogen peroxide using N-hydroxysuccinimide as an efficient catalyst underExpand
Inhibitors of 17β-Hydroxysteroid Dehydrogenases
: The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) play an important role in the regulation of steroid hormones, such as estrogens and androgens, by catalysing the reduction of 17-ketosteroidsExpand
Quinone reductase induction activity of methoxylated analogues of resveratrol.
  • W. Zhang, M. Go
  • Chemistry, Medicine
  • European journal of medicinal chemistry
  • 2007
TLDR
Compared to resveratrol, analogues with ortho-methoxy substituents were found to be more potent inducers of QR and to exert their activity in a qualitatively different manner. Expand
Advances in development of inhibitors of 17beta hydroxysteroid dehydrogenases.
  • D. Poirier
  • Chemistry, Medicine
  • Anti-cancer agents in medicinal chemistry
  • 2009
TLDR
In conclusion, the present review article gives a description of novel inhibitors of 17beta-HSD that were published in 2003-2006 that could be used to block the degradation of estradiol, an attractive strategy for treating osteoporosis and Alzheimer's disease. Expand
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3
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