SYNTHESIS AND ALDOSE REDUCTASE INHIBITORY ACTIVITY OF N-(ARYLSULFONYL)GLYCINES AND N-(AROYL)-N-(ARYLMETHYLOXY)GLYCINES

Some N-(arylsulfonyl)- C and N-(aroyl)-N-(arylmethyloxy)glycines D were synthesised and tested as aldose reductase inhibitors (ARIs). They are structurally related to the previously described ARIs of type A and B, from which they differ owing to the presence of a spacer, an OCH2 group, between the amino-acid nitrogen and the aromatic ring. The inhibitory activity was evaluated on the bovine lens aldose reductase enzyme. Compounds of types C and D show an inhibitory activity which, in the case of compounds D, is very similar to that reported for the parent compounds B. Kinetic studies carried out on the most active compound (8a), reveal that it produces an inhibition which, depending on its concentration, may be either uncompetitive or noncompetitive with respect to the substrate and the cofactor.