Synthesis and activity of new inhibitors of aldosterone biosynthesis.
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.
Viger
A
A
Laboratoire de Chimie Organique Biologique, Université Paris VI, France.
Coustal
S
S
Perard
S
S
Chappe
B
B
Marquet
A
A
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D007700:Kinetics; D000451:Mineralocorticoid Receptor Antagonists / Q000096:biosynthesis*; D011374:Progesterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000451:Mineralocorticoid Receptor Antagonists; D011374:Progesterone