Spiro[fluoreneisothiazolidin]one dioxides: new aldose reductase and L-hexonate dehydrogenase inhibitors

J Med Chem. 1991 Nov;34(11):3229-34. doi: 10.1021/jm00115a011.


The first examples of spiro[fluorene-9,4'- and -9,5'-isothiazolidin]one dioxides (1 and 2) were synthesized and screened for activity as aldose reductase and L-hexonate dehydrogenase inhibitors. Compared to compounds 1, and 9,5'-compounds 2, synthesized from fluorene-9-sulfonamides by alkylation at C(9) with ethyl bromoacetate followed by cyclization, were more active, but relatively nonselective, inhibitors of aldose reductase and L-hexonate dehydrogenase, with IC50 values for in vitro inhibition of both enzymes on the order of 10(-7)-10(-8) M. However, the isomeric 9,4'-compounds 1, prepared by alkylation of fluorene-9-carboxylic acid esters with bromo- or iodomethanesulfonamide followed by cyclization, were more selective inhibitors of L-hexonate dehydrogenase with IC50 values of about 10(-6) M.

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Animals
  • Carbohydrate Dehydrogenases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Rats
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology


  • Enzyme Inhibitors
  • Spiro Compounds
  • Thiazoles
  • Carbohydrate Dehydrogenases
  • L-glucuronate reductase
  • Aldehyde Reductase