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.
Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Acetic Acid / chemical synthesis*
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Acetic Acid / chemistry
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Acetic Acid / pharmacology
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Aldehyde Reductase / antagonists & inhibitors*
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Aldehyde Reductase / chemistry
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Aldehyde Reductase / pharmacology
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Animals
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology
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Cataract / complications
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Cataract / prevention & control*
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Disease Models, Animal
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Galactosemias / complications
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Inhibitory Concentration 50
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Molecular Structure
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Naphthalenes / pharmacology
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Ophthalmic Solutions / pharmacology
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Rats
Substances
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Benzimidazoles
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Enzyme Inhibitors
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Naphthalenes
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Ophthalmic Solutions
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tolrestat
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Aldehyde Reductase
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Acetic Acid