Highly selective aldose reductase inhibitors .2. Optimization of the aryl part of 3-(arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic acids

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 inhi...

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Bibliographic Details
Published inChemical & pharmaceutical bulletin Vol. 45; no. 2; pp. 297 - 304
Main Authors Kotani, T, Ishii, A, Nagaki, Y, Toyomaki, Y, Yago, H, Suehiro, S, Okukado, N, Okamoto, K
Format Journal Article
LanguageEnglish
Published TOKYO Pharmaceutical Soc Japan 01.02.1997
Subjects
Chemistry
Chemistry, Medicinal
Chemistry, Multidisciplinary
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Physical Sciences
Science & Technology
selectivity
DIABETIC COMPLICATIONS
aldose reductase inhibitor
2,4,5-trioxoimidazolidine-1-acetic acid
aldose reductase
diabetic complication
aldehyde reductase
CONGENERS
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Summary: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 powerful AR-inhibitory activity, The chlorosubstituted benzothiazolyl compound showed an AR selectivity of more than 5000 fold.
ISSN:0009-2363