Synthesis and biological evaluation of (l,2,4)triazino(4,3-a) benzimidazole acetic acid derivatives as selective aldose reductase inhibitors

摘要

The acetic acid derivatives of [l,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 (IC50) 0.32muM 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 dehy-drogenase, or glutathione reductase.