Copyright c by The American Society for Pharmacology and Experimental Therapeutics All rights of reproduction in any form reserved. MOLECULAR PHARMACOLOGY. 34:852-562 An ArtificaI Intelligence Approach to the Study of the Structural Moieties Relevant to D

The computer-automated structure evaluation program has been used to study 482 compounds relevant to the inhibition of the aldose reductase enzyme. Major activating/inactivating frag-ments were generated automatically. The significance of these molecular descriptors with respect to the activity of the com-pounds is discussed. The aldose reductase enzyme, AR, involved in the sorbitol pathway (Fig. 1), which is an important mechanism in the regulation of mammalian glucose metabolism, has been found to play a physiologically significant role in the initiation of diabetic complications (1, 2). Therefore, over the past few years, considerable efforts have been made by several research groups to design inhibitors of this enzyme. The enzyme is primarily found in the corneal epithelium, retina, optic nerve, placenta, brain, kidney, muscle, and sperm (3-5)