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Quinoxalin-2(1H)-one based design and synthesisproduced several series of aldose reductase (ALR2) inhibitor candidates.In particular, phenolic structure was installed in the compounds forthe combination of antioxidant activity and strengthening the abilityto fight against diabetic complications. Most of the series 6showed potent and selective effects on ALR2 inhibition withIC50values in the range of 0.032–0.468 μM,and 2-(3-(2,4-dihydroxyphenyl)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid (6e) was the most active.More significantly, most of the series 8revealed notonly good activity in the ALR2 inhibition but also potent antioxidantactivity, and 2-(3-(3-methoxy-4-hydroxystyryl)-2-oxoquinoxalin-1(2H)-yl)acetic acid (8d) was even as strong asthe well-known antioxidant Trolox at a concentration of 100 μM,verifying the C3 p-hydroxystyryl side chain as thekey structure for alleviating oxidative stress. These results thereforesuggest an achievement of multifunctional ALR2 inhibitors having bothpotency for ALR2 inhibition and as antioxidants. [ABSTRACT FROM AUTHOR]

A copper catalyst system for the asymmetric 1,4-hydrosilylation of the α,β-unsaturated carboxylate class was developed by which synthesis of (+)- and (-)-enantiomers of 1,2-benzothiazine-1,1-dioxide acetates has been achieved with a good yield and an excellent level of enantioselectivity. A comparative structure-activity relationship study yielded the following order of aldose reductase inhibition activity: (-)-enantiomers > racemic > (+)-enantiomers. Further, a molecular docking study suggested that the (-)-enantiomer had significant binding affinity and thus increased inhibition activity.