RT Journal Article
SR Electronic
T1 Pharmacophor requirements of the aldose reductase inhibitor site.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 521
OP 531
VO 24
IS 3
A1 P F Kador
A1 N E Sharpless
YR 1983
UL http://molpharm.aspetjournals.org/content/24/3/521.abstract
AB 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.