4-(3′α15′β-dihydroxy-5′β-estran- 17′β-yl)furan-2-methyl alcohol: An anti-digoxin agent with a novel mechanism of action

Joseph Deutsch*, Huang G. Jang, Nura Mansur, Ohad Ilovich, Uri Shpolansky, Dana Galili, Tomer Feldman, Haim Rosen, David Lichtstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The synthesis and some pharmacological properties of 4-(3′α- 15′β-dihydiOxy-5β-estran-17′β9-yl)furan-2-methyl alcohol (16) have been described. The compound was synthesized by reacting a synthetic 3α-benzyloxy-5β-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.

Original languageAmerican English
Pages (from-to)600-606
Number of pages7
JournalJournal of Medicinal Chemistry
Volume49
Issue number2
DOIs
StatePublished - 26 Jan 2006

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