Synthetic cardenolides and related compounds

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Abstract

The medical application of cardenolides and bufadienolides is associated with a high risk, due to their toxicity and the small difference between the therapeutic and toxic doses. In the past few years, increasing attention has been paid to the mechanism of cardiotonic action and the synthesis of cardenolide and bufadienolide analogs which are expected to have better therapeutic indices. A cardenolide analog in which the lactone ring is replaced by a nitrogen-containing unsaturated heterocycle was found to be almost as active as the parent compound. A knowledge of the activity of such compounds would contribute to the question of the structural requirements for a heterocyclic substitutent. Pharmacological examinations have shown that the cardiotonic activity of the 17β-exo-heterocyclic steroids is weaker than that of the parent compound, although the ratio of the therapeutic effect to the toxic effect is favorable. Besides cardiotonic activity, a large number of exo-heterocyclic steroids display a potential as inhibitors of human cytochrome P45017α, the enzyme responsible for the conversion of C21 steroids to the related C19 steroids (androgens). This is a potential approach for the therapeutic treatment of this disease, which frequently exhibits an androgen dependence. This review deals with recent studies of the synthesis of modified cardenolides which are expected to have better cardiotonic activities, and with the synthesis of steroids with a variety of heterocycles at C-17 which have been tested against P45017α.

Original languageEnglish
Pages (from-to)1381-1403
Number of pages23
JournalCurrent Organic Chemistry
Volume8
Issue number14
DOIs
Publication statusPublished - Sep 1 2004

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ASJC Scopus subject areas

  • Organic Chemistry

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