Pharmacophor requirements of the aldose reductase inhibitor site

Recent experimental results suggesting that diabetic pathology can at least in part be directly controlled through inhibition of the enzyme aldose reductase (alditol:NADPH oxidoreductase, EC 1.1.1.21) have spurred great interest in the development of specific inhibitors of this enzyme. Specific structural and electronic similarities of apparently diverse aldose reductase inhibitors have been observed through basic studies which utilize computer molecular modeling, molecular orbital calculations, known structure-activity relationships, and protein-modification reagents such as 2-bromo-4'-nitroacetophenone. From these similarities, a model of the aldose reductase inhibitor site has been postulated along with the pharmacophor requirements for the inhibitors--guidelines which should aid in the rational design of new inhibitors.