Synthesis and rat lens aldose reductase inhibitory activity of some benzopyran-2-ones.
A number of 4,7-disubstituted benzopyran-2-ones were synthesized and evaluated for crude rat lens aldose reductase inhibitory activity. Substituents on position 4 included CH3, CO2H, CH2CO2H, CH = 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, 2-oxo-2H-naphtho[1,2-b]pyran-4-acetic, and 1-naphthylacetic 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 with an IC50 of 0.020 microM, is as potent as sorbinil (IC50 = 0.017 microM) in the crude rat lens aldose reductase assay.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D007908:Lens, Crystalline / Q000201:enzymology*; D051381:Rats; D013329:Structure-Activity Relationship; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001578:Benzopyrans; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase