Structure-activity relationships of steroids with mineralocorticoid activity

Fourteen steroid homologues, belonging to the series of 18-substituted progesterone and 17-hydroxymethylketone derivatives were modeled by both molecular and quantum mechanics. We have studied the dependency of the affinity of these compounds for the hMR (human mineralocorticoid receptor) by means of various parameters describing the structure and its molecular properties. Using variable mapping coupled to a discriminant analysis, this work demonstrates the non-linear relationships between affinity and some structural features. We have constructed a model allowing us to predict the affinity and the activity of new compounds. The principal electronic and structural characteristics leading to a selective affinity and activity were revealed.