SYNTHESIS OF NEW 11-BETA-SUBSTITUTED SPIROLACTONE DERIVATIVES - RELATIONSHIP WITH AFFINITY FOR MINERALOCORTICOID AND GLUCOCORTICOID RECEPTORS

Various steroidal 17-spirolactones substituted in the 11beta-position were synthesized to study the relationship between the nature of the 1 1beta-arm and their affinity for cytosolic mineralocorticoid (MR) and glucocorticoid (GR) receptors prepared from adrenalectomized rabbit ki dney or liver. One of them, the -oxo-19-nor-17-pregna-4,9-diene-21,17- carbolactone derivative, exhibited the same affinity for MR as aldoste rone and a 5-fold higher affinity than mespirenone. Its affinity for G R was found to be relatively low. As suggested by molecular modeling, the marked differences in mineralocorticoid receptor binding affinity could be related to the structural features induced by this 11beta-all enic substituent.