Pharmacophore modeling of substituted 1,2,4-Trioxanes for quantitative prediction of their antimalarial activity.

摘要: A pharmacophore model has been developed for determining the essential structural requirements antimalarial activity from eight series of substituted 1,2,4-trioxanes. The best possessing two aliphatic hydrophobic, one aromatic hydrogen-bond (H-bond) acceptor, and H-bond acceptor (lipid) feature showed an excellent correlation coefficient training (r2training = 0.85) a fair test set (r2test 0.51) molecules. predicts well to other known 1,2,4-trioxanes including those which either are drugs or undergoing clinical trials. In order further validate this model, five were synthesized generated focused library screened activity. observed these molecules was consistent with suggesting that may be useful in design potent agents.