title: Synthesis and aldose reductase inhibitory activity of 2-substituted 6-fluoro-2,3-dihydrospiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5'-dio nes.
abstract: 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.
authors.affiliation: Mie Research Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Japan.
authors.forename: R
authors.initials: R
authors.lastname: Unno
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: T
authors.initials: T
authors.lastname: Kakigami
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
authors.forename: K
authors.initials: K
authors.lastname: Mizuno
authors.forename: Y
authors.initials: Y
authors.lastname: Baba
authors.forename: M
authors.initials: M
authors.lastname: Kurono
mesh_terms: 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
chemical_list: D001578:Benzopyrans; D007093:Imidazoles; D013141:Spiro Compounds; D000449:Aldehyde Reductase