Aldosterone antagonists. 2. Synthesis and biological activities of 11,12-dehydropregnane derivatives.
Several steroid derivatives having the delta 11-pregnane skeleton with a 17-gamma-spirolactone function were synthesized to evaluate their antialdosterone activity and to elucidate the relation between their binding affinity to mineralocorticoid receptor (MR) and their mineralo- and/or antimineralocorticoid activity. Although many of the synthesized compounds showed strong binding affinity for the MR and aldosterone agonist activity, 3-(17 beta-hydroxy-3-oxoandrosta-1,4,6,11-tetraen-17 alpha-yl)propionic acid gamma-lactone exhibited good aldosterone antagonist activity in an in vivo assay. Its in vivo antiandrogenic activity was also found to be relatively weak.
D000315:Adrenalectomy; D000818:Animals; D007668:Kidney / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism; D018161:Receptors, Mineralocorticoid; D011980:Receptors, Progesterone / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D013329:Structure-Activity Relationship
D000451:Mineralocorticoid Receptor Antagonists; D011944:Receptors, Androgen; D018161:Receptors, Mineralocorticoid; D011980:Receptors, Progesterone; D011987:Receptors, Steroid