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It is believed that the aldose reductase (AR, EC 1.1.21), the initial enzyme of sorbitol pathway, plays a significant role in the initiation of diabetic complications. In a search for AR inhibitors, a series of 4-oxo-2-thioxothiazolidine-3-acetic acid derivatives was synthesized and showed the inhibitory activity against AR. (Z, E) -5- (2-Methyl-3-phenyl-2-propenylidene) -4-oxo-2-thioxothiazolidine-3-acetic acid (epalrestat) prevented the accumulation of sorbitol in rat sciatic nerve and rat blood cell, and improved motor nerve conduction velocity of diabetic rats. In clinical studies, epalrestat has shown the improvements in nerve function and subjective symptoms. In Japan, epalrestat was introduced on the market in January, 1992.

Development of Epalrestat (Kinedak): Aldose Reductase Inhibitor.