BIOLOGICAL-ACTIVITIES AND QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS OF SPIRO[IMIDAZOLIDINE-4,4'(1'H)-QUINAZOLINE]-2,2',5(3'H)-TRIONES AS ALDOSE REDUCTASE INHIBITORS

被引：47

作者：

YAMAGISHI, M

YAMADA, Y

OZAKI, K

ASAO, M

SHIMIZU, R

SUZUKI, M

MATSUMOTO, M

MATSUOKA, Y

MATSUMOTO, K

机构：

[1] TANABE SEIYAKU CO LTD,APPL BIOCHEM RES LAB,16-89 KASHIMA 3-CHOME,YODOGAWA KU,OSAKA 532,JAPAN

[2] TANABE SEIYAKU CO LTD,BIOL RES LAB,YODOGAWA KU,OSAKA 532,JAPAN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 11期

关键词：

D O I：

10.1021/jm00089a021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones were prepared and tested for aldose reductase inhibitory activity. The 6'-halogenated derivatives were found to be highly potent in vitro inhibitors of male rabbit lens aldose reductase and in vivo inhibitors of polyol accumulation in the sciatic nerves of galactosemic rats. Of these, (4R)-6'-chloro-3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-trione (67) showed the most potent in vitro and in vivo activities. An oral dose of 3 g/kg of compound 67 caused neither death nor behavioral abnormality in the preliminary acute toxicity study using mice and rats. Compound 67 was selected as a candidate for further evaluation. The quantitative structure-activity relationships in this series are also discussed.

引用

页码：2085 / 2094

页数：10

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