Synthesis and biological evaluation of [1,2,4]triazino[4,3-a] benzimidazole acetic acid derivatives as selective aldose reductase inhibitors

Eur J Med Chem. 2010 Mar;45(3):909-14. doi: 10.1016/j.ejmech.2009.11.031. Epub 2009 Dec 4.

Abstract

The acetic acid derivatives of [1,2,4]triazino[4,3-a]benzimidazole (TBI) were synthesized and tested in vitro and in vivo as selective aldose reductase (ALR2) inhibitors. Compound PS11 showed highest inhibitory activity (IC(50)) 0.32 microM and was found to be effective in preventing cataract development in severely galactosemic rats when administered as an eyedrop solution. All the compounds investigated were selective for ALR2, since none of them inhibited appreciably aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase.

Publication types

  • Retracted Publication

MeSH terms

  • Acetic Acid / chemical synthesis*
  • Acetic Acid / chemistry
  • Acetic Acid / pharmacology
  • Aldehyde Reductase / antagonists & inhibitors*
  • Aldehyde Reductase / chemistry
  • Aldehyde Reductase / pharmacology
  • Animals
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology
  • Cataract / complications
  • Cataract / prevention & control*
  • Disease Models, Animal
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Galactosemias / complications
  • Inhibitory Concentration 50
  • Molecular Structure
  • Naphthalenes / pharmacology
  • Ophthalmic Solutions / pharmacology
  • Rats

Substances

  • Benzimidazoles
  • Enzyme Inhibitors
  • Naphthalenes
  • Ophthalmic Solutions
  • tolrestat
  • Aldehyde Reductase
  • Acetic Acid