Spiro oxazolidinedione aldose reductase inhibitors.
Spiro oxazolidinediones (2) derived from five- and six-membered ring aralkyl ketones are potent aldose reductase inhibitors in vitro and in vivo. Their novel and general synthesis has been devised with alpha-hydroxyimidates (5) and 4-alkoxy-2-oxo-3-oxazolines (6) as key intermediates, since traditional synthetic routes through alpha-hydroxy amides (8) usually led to alpha, beta-unsaturated amides (9). Resolution with cinchonidine afforded optically active spiro oxazolidinediones. Optimum biological activity resided in (4S)-6-chlorospiro [4H-2,3-dihydrobenzopyran-4,5'-oxazolidine]-2',4'-dione (21) and its 6,8-dichloro congener (23).
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012584:Sciatic Nerve / Q000201:enzymology; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D010080:Oxazoles; D013141:Spiro Compounds; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase