Molecular Modeling Studies of Aldose Reductase Inhibitors

Yong S. Lee, Robert Pearlstein, Peter F. Kador

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Molecular modeling studies using the AM1 quantum chemical method and a torsional fitting method have been conducted on a series of aldose reductase inhibitors (ARIs) possessing an ionizable group and/or functional group susceptible to nucleophilic attack with the aim of defining the spatial position of ARI pharmacophores. AM1 quantum chemical calculations were conducted on ARIs possessing only an ionizable group to obtain their optimized geometries. These optimized structures were then superimposed on the model compound spirofluorene-9,5′-imidazolidine-2′,4′- dione (17). This superposition study suggests that a negative charge center residing in the vicinity of the 2′-oxygen of the imidazolidine-2′,4′-dione ring participates in the binding interactions. In addition, the optimized geometries of ARIs possessing both an ionizable group and an electronegative functional group were superimposed on spirofluorene-9,5′-imidazolidine-2′,4′-dione (17). The latter results also suggest the presence of a region where nucleophilic substitution can occur.

Original languageEnglish (US)
Pages (from-to)787-792
Number of pages6
JournalJournal of Medicinal Chemistry
Volume37
Issue number6
DOIs
StatePublished - Mar 1 1994

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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