Structure-activity relationship study of spirolactones. Contribution of the cyclopropane ring to antimineralocorticoid activity

Abstract

Spirolactones inhibit the effects of aldosterone. 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 inactivation to account for the enhanced in vivo activity [in animals].