SYNTHESIS AND ALDOSE REDUCTASE INHIBITORY ACTIVITY OF 2-SUBSTITUTED O[4H-1-BENZOPYRAN-4,4'-IMIDAZOLIDINE]-2',5'-DIONES

Optically active and racemic 2-substituted 3-dihydrospiro[4H-1-benzopy ran-4,4'-imidazolidine] -2',5'-diones were synthesized stereoselective ly from (+)-, (-)-, and luoro-3,4-dihydro-4-oxo-2H-1-benzopyran-2-carb oxyl acid [(+)-1, (-)-1, and(+/-)-1], respectively, for evaluation as new aldose reductase inhibitors. Among these compounds, the 2S,4S comp ounds were found to be more potent inhibitors of aldose reductase in v itro and in vivo than the corresponding 2R,4R enantiomers. The chlorom ethyl compound [(+)-5] showed highly potent activities in inhibiting c ataract formation in the lenses and polyol accumulation in the sciatic nerve of rats.