Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents

Isaac O. Donkor, Yasar S. Abdel-Ghany, Peter F. Kador, Tadashi Mizoguchi, Anita Bartoszko-Malik, Duane D. Miller

Research output: Contribution to journalArticle

4 Scopus citations


Derivatives of alrestatin (1-5) and alconil (6-8) possessing Michael acceptor substituents were synthesized as aldose reductase inhibitors. The alrestatin derivatives demonstrated enhanced aldose reductase inhibitory activity. The most potent reversible inhibitor of the series (compound 3) was 15-fold more active than alrestatin. Additionally, lipophilic analogues of alrestatin selectively inhibited rat lens aldose reductase versus rat kidney aldehyde reductase. Unlike alrestatin derivatives, alconil derivatives with similar substituents did not demonstrate significant reversible or irreversible inhibition of aldose reductase.

Original languageEnglish (US)
Pages (from-to)235-243
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Issue number3
StatePublished - Mar 1999



  • Aldehyde reductase
  • Aldose reductase
  • Alrestatin
  • Diabetic complications
  • Michael acceptors

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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