SPIRO HYDANTOIN ALDOSE REDUCTASE INHIBITORS DERIVED FROM 8-AZA-4-CHROMANONES

A series of spiro hydantoins derived from 8-azachromanones (2,3-dihydro-4H-pyrano[2,3-6]pyridin-4-ones) has been prepared and tested for aldose reductase inhibitory activity. The standard Bucherer-Bergs conditions had to be drastically modified to increase yields from less than 1% to an acceptable 50% range. One of the most potent compounds was m-6'-chloro-2',3'-dihydro-2'-methylspiro[imidazolidine-4,4'-4'H-pyrano[2,3-b]pyridine;-2,5-dione; resolution of this compound showed that the 2'R,4’S enantiomer 16 was the most active spiro hydantoin in this series with an IC50 of 7.5 X 10-9 against human placenta aldose reductase. © 1990, American Chemical Society. All rights reserved.