A Free‐Wilson Analysis of 5β,14β‐Androstane Derivatives Inhibiting the Na/K‐ATPase from Human Heart

A Free-Wilson analysis of 95 digitalis-like steroids inhibiting the Na/K-ATPase is presented. The chosen parent structure – 5β,14β-androstane-3β,14-diol – was varied at 12 individual substitution sites. The high significance of the multiple regression of the data obtained with the great majority of the derivatives tested revealed the general applicability of the additivity model, allowing the prediction of the potency of hypothetical compounds from the derived 57 de novo substituent constants. Derivatives carrying voluminous substituents at C3 or C17, in which the cis/trans/cis-junction of the steroid rings were altered, disclosed incompatibilities with the model.