Spiro oxazolidinedione aldose reductase inhibitors

J Med Chem. 1982 Dec;25(12):1451-4. doi: 10.1021/jm00354a012.

Abstract

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).

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Animals
  • Chemical Phenomena
  • Chemistry
  • In Vitro Techniques
  • Oxazoles / chemical synthesis*
  • Oxazoles / pharmacology
  • Rats
  • Sciatic Nerve / enzymology
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / pharmacology
  • Stereoisomerism
  • Sugar Alcohol Dehydrogenases / antagonists & inhibitors*

Substances

  • Oxazoles
  • Spiro Compounds
  • Sugar Alcohol Dehydrogenases
  • Aldehyde Reductase