Aldosterone antagonists. 1. Synthesis and activities of 6 beta,7 beta:15 beta,16 beta-dimethylene steroidal spirolactones.
Several derivatives of the highly active aldosterone antagonists dihydrospirorenone (2) and spirorenone (3) were synthesized. The purpose of these efforts was to prepare compounds exhibiting reduced endocrinological properties with the same or better aldosterone antagonistic activity than that of spirorenone. The 1 alpha,2 alpha-methylene derivative 20 has a similar aldosterone antagonistic potency compared to that of spirorenone but does not show decreased endocrinological side effects. Other substituents as in compounds 4-11, 15-19, and 21 sharply decreased the aldosterone antagonistic activity of 2 or 3, respectively.
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D005260:Female; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000138:chemical synthesis*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000730:Androstadienes; D000451:Mineralocorticoid Receptor Antagonists; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D013148:Spironolactone; C035143:spirorenone