Synthesis and activity of new inhibitors of aldosterone biosynthesis

• Published in: Journal of steroid biochemistry Vol. 30; no. 1-6; p. 469
• Main Authors: Viger, A, Coustal, S, Perard, S, Chappe, B, Marquet, A
• Format: Journal Article
• Language: English
• Published: England 1988
• Subjects: Adrenal Glands - drug effects; Adrenal Glands - metabolism; Animals; Kinetics; Mineralocorticoid Receptor Antagonists - biosynthesis; Progesterone - analogs & derivatives; Progesterone - chemical synthesis; Progesterone - pharmacology; Rats; Rats, Inbred Strains; Structure-Activity Relationship
• ISSN: 0022-4731
• DOI: 10.1016/0022-4731(88)90145-8

A new family of aldosterone biosynthesis inhibitors, designed as 18-mono-oxygenase, cytochrome-P450-dependent, potential Kcat inhibitors, is described. These compounds are progesterone derivatives substituted at the 18-methyl group. Preliminary results on the in vitro biological evaluation of these modified progesterones are presented. Aldosterone biosynthesis is completely inhibited by 18-vinyl progesterone 5 at a concentration of 0.8 microM and by 18-ethynyl progesterone 6 at 8 microM. It appears that products designed as alkylating agents for the prosthetic heme group are the most potent inhibitors in that series.