Phenylsulfonylnitromethanes as potent irreversible inhibitors of aldose reductase

Aldose reductase (AR) inhibition provides a viable pharmacologically direct mode for the treatment of diabetic complications. We have synthesized a se ries of N-4 substituted analogues (15-21) of the known aldose reductase inh ibitor phenyl-sulfonylnitromethane. The compounds are potent inhibitors of AR with IC(50)s between 0.01 and 0.19 mu M Some of the compounds are also p otent affinity labels for AR. Compound 19 exhibits the highest and almost c omplete irreversible inhibition of AR known to date. (C) 1999 Editions scie ntifiques et medicales Elsevier SAS.