Synthesis, absolute configuration, and conformation of the aldose reductase inhibitor sorbinil

J Med Chem. 1985 Nov;28(11):1716-20. doi: 10.1021/jm00149a030.

Abstract

The aldose reductase inhibitor 2,3-dihydro-6-fluorospiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5 '-dione was resolved into its enantiomers. Sorbinil, the S isomer, was found to be a better inhibitor of the enzyme in vitro and in vivo than the corresponding R isomer. X-ray data on sorbinil, which were used to determine its absolute configuration, are presented. NMR studies of sorbinil in solution indicate the existence of two conformers with a low energy barrier for interconversion.

Publication types

  • Comparative Study

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Chemical Phenomena
  • Chemistry, Physical
  • Crystallization
  • Imidazoles / chemical synthesis
  • Imidazoles / pharmacology*
  • Imidazolidines*
  • Isomerism
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Sugar Alcohol Dehydrogenases / antagonists & inhibitors*
  • Thermodynamics
  • X-Ray Diffraction

Substances

  • Imidazoles
  • Imidazolidines
  • Sugar Alcohol Dehydrogenases
  • Aldehyde Reductase
  • sorbinil