Quantitative structure-activity relationships in 1-aryl-2-(alkylamino)ethanol antimalarials.
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.
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008954:Models, Biological; D010616:Phenanthrenes / Q000494:pharmacology; D010962:Plasmodium berghei; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000962:Antimalarials; D004983:Ethanolamines; D010616:Phenanthrenes; D011725:Pyridines; D011804:Quinolines