title: 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.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. odj@cc.huji.ac.il
authors.forename: Joseph
authors.initials: J
authors.lastname: Deutsch
authors.forename: Huang G
authors.initials: HG
authors.lastname: Jang
authors.forename: Nura
authors.initials: N
authors.lastname: Mansur
authors.forename: Ohad
authors.initials: O
authors.lastname: Ilovich
authors.forename: Uri
authors.initials: U
authors.lastname: Shpolansky
authors.forename: Dana
authors.initials: D
authors.lastname: Galili
authors.forename: Tomer
authors.initials: T
authors.lastname: Feldman
authors.forename: Haim
authors.initials: H
authors.lastname: Rosen
authors.forename: David
authors.initials: D
authors.lastname: Lichtstein
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D004077:Digoxin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D004962:Estranes / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D011869:Radioligand Assay; D013574:Synaptosomes / Q000378:metabolism; D014168:Transferrin / Q000096:biosynthesis
chemical_list: C508796:4-(3',15'-dihydroxy-5'-estran-17'-yl)furan-2-methyl alcohol; D004962:Estranes; D014168:Transferrin; D004077:Digoxin