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Anticataract Activity of Analogs of a Sorbitol Dehydrogenase Inhibitor

Anticataract Activity of Analogs of a Sorbitol Dehydrogenase Inhibitor

Peter F Kador, Jun Inoue, Karen Blessing

J Ocul Pharmacol Ther. 2004 Aug;20(4):333-44.

PMID: 15321028

Abstract:

The initiation of sugar cataract formation by the aldose reductase catalyzed accumulation of sorbitol in diabetic rats, and its prevention by the administration of aldose reductase inhibitors at the onset or early stages of diabetes, has been well established. In contrast, the inhibition of sorbitol dehydrogenase by 4-[4-(N,N-dimethylsulfamoyl)piperazino]-2-hydroxymethylpyrimidine (SDI-1) has been observed to increase the onset in severity of sugar cataract formation in diabetic rats. Two analogs of SDI-1 have been synthesized, where the 4-(2-hydroxymethyl)pyrimidine ring has been replaced with either a 4-(2,6-dimethoxy)-pyrimidine ring or a 2-pyrimidine ring. Neither compound, 2-[4-(N,N-dimethylsulfamoyl)piperazino]-pyrimidine (SRA-1) or 4-[4-(N,N-dimethylsulfamoyl) piperazino]-2,6-dimethoxypyrimidine (SRA-2), demonstrated significant sorbitol dehydrogenase or aldose reductase inhibition. Oral administration of these compounds to streptozotocin diabetic rats, however, delayed cataract formation without reducing the levels of hyperglycemia or lens polyol.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP139332642	4-(N,N-Dimethylsulfamoyl)-7-piperazino-benzofurazan		139332-64-2	Price

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