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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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
Volume34
Issue number3
DOIs
StatePublished - Jan 1 1999

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Aldehyde Reductase
Bioactivity
Derivatives
Rats
Lenses
alrestatin
Kidney

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents. / Donkor, Isaac; Abdel-Ghany, Yasar S.; Kador, Peter F.; Mizoguchi, Tadashi; Bartoszko-Malik, Anita; Miller, Duane.

In: European Journal of Medicinal Chemistry, Vol. 34, No. 3, 01.01.1999, p. 235-243.

Research output: Contribution to journalArticle

Donkor, Isaac ; Abdel-Ghany, Yasar S. ; Kador, Peter F. ; Mizoguchi, Tadashi ; Bartoszko-Malik, Anita ; Miller, Duane. / Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents. In: European Journal of Medicinal Chemistry. 1999 ; Vol. 34, No. 3. pp. 235-243.
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