Synthesis and aldose reductase inhibitory activity of substituted 2(1H)-benzimidazolone- and oxindole-1-acetic acids

Article abstract of DOI:10.1016/0223-5234(92)90112-E

Potent in vitro inhibition of the enzyme aldose reductase (AR) was observed with several members of a series of 3-alkylated 2(1H)-benzimidazolone-1-acetic acids, as well as with analogs from a structurally-related series of oxindole-1-acetic acids with 3-alkyl or 3-alkylidene substituents.Intrinsic activity against AR was, in general, greatest in compounds from the second series, especially with analogs which containalkylidene side chains, with typical IC50 values of <*> 1 μM.However, in streptozotocindiabetic rat model, the best compounds from either series failedto prevent sorbitol accumulation in lens or sciatic nerve to the degree observed with AR inhibitors such as ponalrestat or zopolrestat. aldose reductase / diabetes / 2(1H)-benzimidazolone-1-acetic acid / oxindole-1-acetic acid