A structure-activity relationship study of spirolactones. Contribution of the cyclopropane ring to antimineralocorticoid activity.
A series of spirolactones containing a cyclopropane ring in the molecule was examined for its effects on the mineralocorticoid receptor. The results were compared with those of a similar series of spirolactones in which the cyclopropane ring was replaced by a double bond. Insertion of a double bond or an alpha-cyclopropane ring into the 1,2 or the 6,7 position leads to a reduction in the binding affinity. The pi-bonding system of the beta-cyclopropane ring at C-6 and C-7 does not promote binding to the receptor. The presence of the 6 beta, 7 beta-cyclopropane ring may deter metabolic activation to account for the enhanced in vivo activity.
D055598:Chemical Phenomena; D002621:Chemistry; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D013148:Spironolactone