4-(3'alpha15'beta-Dihydroxy-5'beta-estran-17'beta-yl)furan-2-methyl Alcohol: An Anti-Digoxin Agent with a Novel Mechanism of Action

摘要

The synthesis and some pharmacological properties of 4-(3'alpha-15'beta-dihydroxy-5beta-estran-17'beta-yl)furan-2-methyl alcohol (16) have been described.The compound was synthesized by reacting a synthetic 3alpha-benzyloxy-5beta-estr-15-en-17-one with the ethylene acetal of 4-bromo-2-furancarboxyaldehyde,followed by hydrolysis of the ethylene acetal and reduction of the aldehyde.Despite its resemblance to the structure of cardiac steroids (CS),16 does not bind to the CS receptor on Na~+,K~+-ATPase and does not increase the force of contraction of heart muscle.However,16 inhibited the digoxin-induced increase in the force of contraction and arrhythmias in guinea pig papillary muscle and human atrial appendages.The steroid also inhibited digoxin-induced alteration in endocytosed membrane traffic,indicating a novel mechanism of action.