Synthesis and aldose reductase inhibitory activities of novel N-nitromethylsulfonanilide derivatives

A novel series of 14 N-nitromethylsulfonanilide derivatives were synthesize d and evaluated for their ability to inhibit recombinant aldose reductase. Computational docking simulations provided a good explanation for the obser ved structure-activity relationships. Kinetic analysis of (2-fluoro-5-methy l-N-methyl)-N-nitromethylsulfonanilide 11, one of the most potent compounds in this series with an IC50 = 0.35 mu M, showed uncompetitive inhibition. Subsequent in vitro culture studies of rat lenses with 11 indicated that th is series of aldose reductase inhibitors are effective in either preventing or retarding sugar cataract formation associated with diabetes. (C) 2000 E lsevier Science Ltd. All rights reserved.