Quantitative structure-activity relationships in 1-aryl-2-(alkylamino)ethanol antimalarials
Ki Hwan Kim, Corwin H. Hansch, James Y. Fukunaga, Edward E. Steller, Priscilla Y. C. Jow, Paul N. Craig, June Page · Journal of Medicinal Chemistry · 1979
A quantitative structure-activity relationship has been formulated for 646 antimalarials acting against P. berghei in mice. The equation developed has 14 terms, 9 of which are indicator variables. The correlation coefficient for the QSAR is 0.898 and the standard deviation is 0.309. The antimalarials are all arylcarbinols of the type X-ArCHOHCH2NR1R2. Sixty different aryl structures, including a variety of heterocyles, are contained in the study. The most important determinate of activity is found to be the electron-withdrawing ability of the substituents X; the hydrophobic character of X and R plays less important roles. Suggestions for more potent analogues are made and the lack of activity of about 100 additional analogues is also considered.