ChemInform Abstract: Synthesis of Pyridazine Acetic Acid Derivatives Possessing Aldose Reductase Inhibitory Activity and Antioxidant Properties

N -Acetic acid derivatives of 4-carboxy-6-arylpyridazin-3-ones were synthesized for the dual purpose of inhibiting aldose reductase and exhibiting antioxidant properties. All the prepared compounds showed a significant in vitro aldose reductase inhibitory effect (10 −5 M ≤ IC 50 ≤ 10 −4 M). The spatial configuration of the most active derivative 4f (4- i -PrC 6 H 4 at C 6 , IC 50 = 0 95 × 10 −5 M) was compared with pharmacophore requirements of the aldose reductase inhibitor site using a molecular modeling system. The antioxidant action of 4a–f was also studied in vitro . Compound 4c (4-ClC 6 H 4 at C 6 , IC 50 = 1.56 × 10 −3 M) was the most effective at scavenging the superoxide anion whereas compound 4a (C 6 H 5 at C 6 , IC 50 = 1.28 × 10 −3 M) was the most active at inhibiting lipid peroxidation. In addition, biological activities (log 1/IC 50 ) for most of the data sets could be correlated directly to lipophilic, electronic and steric parameters.