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

doi:10.1021/jm0505819

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 journal › Article › peer-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 language	English
Pages (from-to)	600-606
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	2
DOIs	https://doi.org/10.1021/jm0505819
State	Published - 26 Jan 2006

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title = "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",

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.",

author = "Joseph Deutsch and Jang, {Huang G.} and Nura Mansur and Ohad Ilovich and Uri Shpolansky and Dana Galili and Tomer Feldman and Haim Rosen and David Lichtstein",

year = "2006",

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doi = "10.1021/jm0505819",

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AU - Deutsch, Joseph

AU - Jang, Huang G.

AU - Mansur, Nura

AU - Ilovich, Ohad

AU - Shpolansky, Uri

AU - Galili, Dana

AU - Feldman, Tomer

AU - Rosen, Haim

AU - Lichtstein, David

PY - 2006/1/26

Y1 - 2006/1/26

N2 - 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.

AB - 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.

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ER -

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

Abstract

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