Aldose reductase inhibitors chemistry

M.. and Rastelli, G. (2007) Validation of an automated procedure for the prediction of relative free energies of binding on a set of aldose reductase inhibitors. Bioorganic Medicinal Chemistry, IS, 7865-7877. 

In 1982 Ayerst Laboratories in Montreal became the first company in Canada to install a commercial software tool (the SYBYL suite from Tripos Associates) to help in the development of pharmacophoric models from structure-activity relationships. The installation of the software was the second ever, worldwide, by a company and is a testimonial to the foresight of the director of medicinal chemistry, Dr. Leslie Humber, for having championed its installation. Dr. Adi M. Treasurywala, then an organic chemist with some experience in medicinal chemistry, became the first industrial computational chemist in Canada that year. The use of modeling approaches contributed in a minor but significant way to the discovery of the compound known as Tolrestat, which was an inhibitor of lens aldose reductase. This led to the acknowledgment of Treasurywala as a coinventor of the drug on several patents that were filed in this research area. Approximately in 1983, Ayerst closed down its discovery effort in Canada and moved to Princeton, New Jersey, where an expanded effort in the area of computational chemistry continues. 

A considerable medicinal chemistry effort has gone into devising inhibitors of aldose reductase their inhibition shows a dominant or even exclusive anticompetitive component when measured as inhibitors of aldose reduction, since they form tight complexes of the form E.NAD.I the inhibition is competitive when alditol oxidation is measured. 

CURRENT STATUS OF THE CHEMISTRY AND SYNTHESIS OF NATURAL ANTIMALARIAL COMPOUNDS AND NATURAL SUBSTANCES USED TO ALLEVIATE SYMPTOMS OF DIABETES (ALDOSE REDUCTASE AND A-GLUCOSIDASE INHIBITORS)... 

Rastelli, G., Ferrari, A.M., Costantino, L., and Gamberini, M.C. (2002) Discovery of new inhibitors of aldose reductase from molecular docking and database screening. Bioorganic S, Medicinal Chemistry Letters, 10, 1437-1450. 

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