Aldosterone antagonists. 3. Synthesis and activities of steroidal 7 alpha-(alkoxycarbonyl)-15,16-methylene spirolactones

Several A- and D-ring substituted steroidal 7 alpha-alkoxycarbonyl spirolactones were synthesized with the purpose of increasing the aldosterone antagonistic potency and reducing the endocrinological side effects relative to the standard drug spironolactone. It was found that the 15 beta,16 beta-met...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1990-02, Vol.33 (2), p.509-513
Main Authors: Nickisch, K, Bittler, D, Laurent, H, Losert, W, Nishino, Y, Schillinger, E, Wiechert, R
Format: Article
Language:English
Subjects:
Animals
Biological Assay
Chemical Phenomena
Chemistry
Female
Male
Mineralocorticoid Receptor Antagonists - chemical synthesis
Mineralocorticoid Receptor Antagonists - metabolism
Orchiectomy
Ovulation - drug effects
Pregnadienes - chemical synthesis
Pregnadienes - pharmacology
Pregnancy
Rabbits
Rats
Rats, Inbred Strains
Receptors, Androgen - metabolism
Receptors, Progesterone - metabolism
Spironolactone - analogs & derivatives
Spironolactone - chemical synthesis
Spironolactone - pharmacology
Structure-Activity Relationship
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Summary:Several A- and D-ring substituted steroidal 7 alpha-alkoxycarbonyl spirolactones were synthesized with the purpose of increasing the aldosterone antagonistic potency and reducing the endocrinological side effects relative to the standard drug spironolactone. It was found that the 15 beta,16 beta-methylene derivative 17 exhibited a 2-fold higher aldosterone antagonistic activity compared to either spironolactone or the 15,16-unsubstituted derivative 29 while showing remarkably reduced antiandrogenicity.
ISSN:0022-2623
DOI:10.1021/jm00164a007