Synthesis and rat lens aldose reductase inhibitory activity of some benzopyran-2-ones

Publisher Website
Google Scholar
Abstract
A number of 4,7-disubstituted benzopyran-2-ones (4-24) were synthesized and evaluated for crude rat lens aldose reductase inhibitory activity. Substituents on position 4 included CH3, CO2H, CH2CO2H, CH.dbd.CHCO2H, and CH2CH2CO2H. The aromatic substituents included OH, OCH3, OCOCH3, CH2CH3, and Cl. Also included in the study were 3-oxo-3H-naphtho[2,1-b]pyran-1-acetic (25), 2-oxo-2H-naphtho[1,2-b]pyran-4-acetic (26), and 1-naphthylacetic (30) acids. The benzopyran and naphthopyran derivatives were prepared by the classical von Pechmann reaction. General structure-activity relationships reveal that optimal enzyme inhibitory activity is displayed by those compounds possessing the acetic acid moiety. For example, the most potent derivative, 3-oxo-3H-naphtho[2,1-b]pyran-1-acetic acid (25) with an IC50 of 0.020 .mu.M, is as potent as sorbinil (IC50 = 0.017 .mu.M) in the crude rat lens aldose reductase assay.