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.