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 11beta-arm and their affinity for cytosolic mineralocorticoid (MR) and glucocorticoid (GR) receptors prepared from adrenalectomized rabbit kidney or liver. One of them, the 11beta-allenyl-3-oxo-19-nor-17-pregna-4,9-diene-21,17-carbolactone derivative, exhibited the same affinity for MR as aldosterone and a 5-fold higher affinity than mespirenone. Its affinity for GR 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-allenic substituent.