Recent advances in aldose reductase inhibitors: potential agents for the treatment of diabetic complications

The development of long-term diabetic complications in diabetes patients is considered to be closely related to hyperglycaemia. Aldose reductase was first found to be implicated in the aetiology of secondary complications of diabetes. A variety of structurally diverse compounds have been observed to inhibit aldose reductase and effective, orally-active inhibitors of the enzyme have been investigated for almost 30 years. Although several of these compounds have progressed to the clinical level, only a few are currently on the market. Furthermore, the number of patents related to aldose reductase inhibitors has declined during recent years, whereas the number for other compounds, such as the inhibitors of the formation of advanced glycated end products and antioxidants, has increased. In this review, recent patents relevant to aldose reductase inhibitors are presented, following a short summary of early works. Lastly, rational approaches to the discovery of aldose reductase inhibitors are briefly reviewed.