Synthesis and aldose reductase inhibitory activity of 2-substituted 6-fluoro-2,3-dihydrospiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5'-dio nes.
Optically active and racemic 2-substituted 6-fluoro-2,3-dihydrospiro[4H-1- benzopyran-4,4'-imidazolidine]-2',5'-diones were synthesized stereoselectively from (+)-, (-)-, and (+/-)-6-fluoro-3, 4-dihydro-4-oxo-2H-1-benzopyran-2-carboxylic acid [(+)-1, (-)-1, and (+/-)-1], respectively, for evaluation as new aldose reductase inhibitors. Among these compounds, the 2S,4S compounds were found to be more potent inhibitors of aldose reductase in vitro and in vivo than the corresponding 2R,4R enantiomers. The chloromethyl compound [(+)-5] showed highly potent activities in inhibiting cataract formation in the lenses and polyol accumulation in the sciatic nerve of rats.
Unno
R
R
Mie Research Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Japan.
Yamaguchi
T
T
Usui
T
T
Kakigami
T
T
Fukushima
M
M
Mizuno
K
K
Baba
Y
Y
Kurono
M
M
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D002386:Cataract / Q000517:prevention & control; D005693:Galactosemias / Q000097:blood; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007908:Lens, Crystalline / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D001578:Benzopyrans; D007093:Imidazoles; D013141:Spiro Compounds; D000449:Aldehyde Reductase