Chemical and Pharmaceutical Bulletin p. 297 - 304 (1997)
Update date:2022-07-30
Topics:
Kotani, Takayuki
Ishii, Akira
Nagaki, Yasuhiro
Toyomaki, Yoshio
Yago, Hisashi
Suehiro, Seishi
Okukado, Nobuhisa
Okamoto, Kaoru
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 chloro- substituted benzothiazolyl compound showed an AR selectivity of more than 5000 fold.
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