Synthesis and aldose reductase inhibitory activity of 2-substituted-6-fluoro-2,3-dihydrospiro [4H-1-benzopyran-4, 4'-imidazolidine]-2',5'-diones.
Optically active and racemic 2-substituted-6-fluoro-2,3-dihydrospiro[4H-1-benzopyran-4, 4'-imidazolidine]-2',5'-diones were synthesized from (+)-, (-)-, and (+-)-6-fluoro-3,4-dihydro-4-oxo-2H-1-benzopyran-2-carboxylic acid. These compounds were then evaluated for in vitro and in vivo aldose reductase inhibitory activity. The 2S,4S isomers were found to be more potent aldose reductase inhibitors than the other corresponding stereoisomers. Among these compounds, (2S,4S)-6-fluoro-2,3-dihydro-2',5'-dioxospiro[4H-1-benzopyran-4, 4'-imidazolidine]-2-carboxamide ((+)-1b, SNK-860, CAS 105300-43-4) showed the most potent in vitro and in vivo activity.
Yamaguchi
T
T
Mie Research Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Japan.
Miura
K
K
Usui
T
T
Unno
R
R
Matsumoto
Y
Y
Fukushima
M
M
Mizuno
K
K
Kondo
Y
Y
Baba
Y
Y
Kurono
M
M
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism
D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D013141:Spiro Compounds; C077139:fidarestat; D000449:Aldehyde Reductase