Highly Selective Aldose Reductase Inhibitors. II. Optimization of the Aryl Part of 3-(Arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic Acids

概要

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Accumulation of intracellular sorbitol, the product of glucose reduction catalyzed by aldose reductase (AR) [EC 1.1.1.21], is thought to be the main culprit in the development of diabetic complications. A series of 3-arylalkyl-2,4,5-trioxoimidazolidine-1-acetic acids was prepared and tested for inhibitory activities towards AR and aldehyde reductase (ALR) [EC 1.1.1.2]. These derivatives showed strong inhibitory activity against AR without markedly inhibiting ALR. In particular, the compounds with 3-nitrophenyl, 4-chloro-3-nitrophenyl, and chloro-substituted benzothiazolyl groups as the aryl part showed poweful AR-inhibitory activity. The chlorosubstituted benzothiazolyl compound showed an AR selectivity of more than 5000 fold.
公益社団法人日本薬学会の論文
1997-02-15