Document Report Card

ID: ALA1122259

Journal: J Med Chem

Title: Combined distance geometry analysis of dihydrofolate reductase inhibition by quinazolines and triazines.

Authors: Ghose AK, Crippen GM.

Abstract: Guided by the success of distance geometry in explaining the inhibition of dihydrofolate reductase by 68 quinazolines, we have made a combined analysis on the inhibition of rat liver dihydrofolate reductase by 33 triazines and 15 quinazolines. The model gave a fit having the correlation coefficient 0.892 and root mean square (rms) deviation 0.596 in log (1/C50) units. The model was applied to predict the biological activity of 91 compounds. The predicted values showed an rms deviation of 0.907 and a correlation coefficient of 0.790. The present study suggested the synthesis of some triazines as possible potent dihydrofolate inhibitors. The site geometry was compared with the crystal structure of a triazine bound to chicken liver dihydrofolate reductase, and a good correlation has been found.

CiteXplore: 6864738

DOI: 10.1021/jm00361a012