Selective Irreversible Inhibitors of Aldose Reductase

Michael W. Smar, Jeffrey J. Ares, Duane Miller, Toshihiro Nakayama, Hiroyuki Itabe, Peter F. Kador

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

A series of 5-substituted-1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid analogues have been examined as irreversible inhibitors of aldose reductase. The 5-α-bromoacetamide and 5-α-iodoacetamide analogues 5 and 6 gave irreversible inhibition of aldose reductase while the 5-α-chloroacetamide analogue 3 did not show this type of inhibition. Protection studies indicate that irreversible inhibitions are occurring at the inhibitor binding site. Comparative irreversible inhibition studies with rat lens aldose reductase (RLAR) and rat kidney aldehyde reductase (RKALR) indicate that 5-α-haloacetamide analogues 5 and 6 are much more effective inhibitors of RLAR.

Original languageEnglish (US)
Pages (from-to)1117-1120
Number of pages4
JournalJournal of Medicinal Chemistry
Volume35
Issue number6
DOIs
StatePublished - Mar 1 1992
Externally publishedYes

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Aldehyde Reductase
Lenses
Iodoacetamide
Acetic Acid
Binding Sites
Kidney

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Smar, M. W., Ares, J. J., Miller, D., Nakayama, T., Itabe, H., & Kador, P. F. (1992). Selective Irreversible Inhibitors of Aldose Reductase. Journal of Medicinal Chemistry, 35(6), 1117-1120. https://doi.org/10.1021/jm00084a017

Selective Irreversible Inhibitors of Aldose Reductase. / Smar, Michael W.; Ares, Jeffrey J.; Miller, Duane; Nakayama, Toshihiro; Itabe, Hiroyuki; Kador, Peter F.

In: Journal of Medicinal Chemistry, Vol. 35, No. 6, 01.03.1992, p. 1117-1120.

Research output: Contribution to journalArticle

Smar, MW, Ares, JJ, Miller, D, Nakayama, T, Itabe, H & Kador, PF 1992, 'Selective Irreversible Inhibitors of Aldose Reductase', Journal of Medicinal Chemistry, vol. 35, no. 6, pp. 1117-1120. https://doi.org/10.1021/jm00084a017
Smar, Michael W. ; Ares, Jeffrey J. ; Miller, Duane ; Nakayama, Toshihiro ; Itabe, Hiroyuki ; Kador, Peter F. / Selective Irreversible Inhibitors of Aldose Reductase. In: Journal of Medicinal Chemistry. 1992 ; Vol. 35, No. 6. pp. 1117-1120.
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