Quantitative structure-activity relationships in 1-aryl-2-(alkylamino)ethanol antimalarials

Abstract
A quantitative structure-activity relationship was formulated for 646 antimalarials acting against Plasmodium berghei in mice. The equation developed has 14 terms, 9 of which were indicator variables. The correlation coefficient for the QSAR was 0.898 and the SD was 0.309. The antimalarials were all arylcarbinols of the type X-ArCHOHCH2NR2R2. Sixty different aryl structures, including a variety of heterocycles, were contained in the study. The most important determinate of activity was the electron-withdrawing ability of the substituents X; the hydrophobic character of X and R played less important roles. Suggestions for more potent analogues were made and the lack of activity of about 100 additional analogues was also considered.