VARIABLE MAPPING OF STRUCTURE-ACTIVITY-RELATIONSHIPS - APPLICATION TO17-SPIROLACTONE DERIVATIVES WITH MINERALOCORTICOID ACTIVITY

Fifty-four steroid homologs, belonging to the series of 17-spirolacton es, were modelled by molecular and quantum mechanics. We studied the a ffinity of these compounds for the cytosolic mineralocorticoid recepto r by way of various parameters describing each structure and its molec ular properties. After the failure of a classic preliminary QSAR study , demonstrating the nonlinear relationships between affinity and struc tural descriptors, we constructed a model allowing us to predict the a ffinity of new compounds. Our method is based on simple graphic tools coupled to a cluster significance analysis. A complementary study of t he activity relating the prediction of the antagonist/agonist characte r of 37 high-affinity compounds was also carried out using the same me thodology. The principal electronic and structural characteristics lea ding to a selective activity were revealed.