Inhibitory Effect of Benzyl Oxazolecarbamate Analogues on Aldose Reductase

概要

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Twelve kinds of benzyl oxazolecarbamate analogues were tested in vitro for inhibition of aldose reductases, which play a leading role in the etiology of diabetic complications such as cataract, retinopathy and neuropathy. The comparative study of various analogues substituted with a benzylcarbamate group at C-2,C-4 of C-5 of the oxazole skeleton showed that the benzylcarbamate group at the C-2 position was absolutely necessary for potent aldose reductase inhibitory activity.The group at C-4 of C-5 was ineffective. Introduction of an alkyl group at the C-4 position of benzyl 5-phenyl-2-oxazolecarbamate increased the inhibitory activity, and in particular, the 4-isopropyl analogue was found to be a potent inhibitor. The 50% inhibition concentration of benzyl 4-isopropyl-5-phenyl-2-oxazolecarbamate (IV) for aldose reductases Ia and Ib was about 3.5×10^<-7>M, whereas that of benzyl 5-phenyl-2-oxazolecarbamate (I) was about 1.5×10^<-5>M. Inhibition of rabbit lens aldose reductase by compound IV was of a non-competitive type with DL-glyceraldehyde as a substrate. Compound IV appears to be a specific inhibitor of rabbit lens aldose reductase, because it was found to have little inhibitory effect against several other enzymes.
社団法人日本薬学会の論文
1986-06-25