Conformation of (Z)-3-carboxymethyl-[(2E)-2-methyl-3-phenylpropenylidene]rhodanine (epalrestat), a potent aldose reductase inhibitor: X-ray crystallographic, energy calculational, and nuclear magnetic resonance studies

Abstract

In order to examine the conformational characteristics of aldose reductase inhibitors, the conformational analysis of epalrestat (ONO-2235) has been carried out by X-ray crystallographic, energy calculational, and nuclear magnetic resonance methods. The chemical structure which had previously been proposed for epalrestat has been revised by the X-ray single-crystal analysis. The extremely planar conformation observed in the crystal structure is shown to be energetically the most stable form and is the predominant form in solution. The characteristic conformation is discussed with respect to the aldose reductase inhibitory activity.