HIGHLY SELECTIVE ALDOSE REDUCTASE INHIBITORS .1. 3-(ARYLALKYL)-2,4,5-TRIOXOIMIDAZOLIDINE-1-ACETIC ACIDS

Authors
ISHII A KOTANI T NAGAKI Y SHIBAYAMA Y TOYOMAKI Y OKUKADO N IENAGA K OKAMOTO K
Citation
A. Ishii et al., HIGHLY SELECTIVE ALDOSE REDUCTASE INHIBITORS .1. 3-(ARYLALKYL)-2,4,5-TRIOXOIMIDAZOLIDINE-1-ACETIC ACIDS, Journal of medicinal chemistry, 39(9), 1996, pp. 1924-1927
Citations number
21
Categorie Soggetti
Chemistry Medicinal
Journal title
Journal of medicinal chemistry → ACNP
ISSN journal
00222623
Volume
39
Issue
9
Year of publication
1996
Pages
1924 - 1927
Database
ISI
SICI code
0022-2623(1996)39:9<1924:HSARI.>2.0.ZU;2-Q
Abstract
A series of 3-(arylalkyl)-2,4,5-trioxoimidazolidine-1-acids (1) was pr epared and tested for aldose reductase (AR) and aldehyde reductase (AL R) inhibitory activities. These compounds showed strong inhibitory act ivity against AR without significant inhibitory activity for ALR. The ratio of IC50(ALR)/IC50(AR) was > 1000 in some compouds. On the basis of pharmacological tests such as the recovery of reduced motor nerve c onduction velocity and toxicological profile, 3-(3-nitrobenzyl)-2,4,5- trioxoimidazolidine-1-acid (NZ-314) was selected as the candidate for clinical development.