The increasing resistance of the malarial parasite to antimalarial drugs is a 
major contributor to the reemergence of the disease and increases the need for 
new drug targets. The two aspartic proteases, plasmepsins I and II, from 
Plasmodium falciparum have recently emerged as potential targets. In an effort 
to inhibit these hemoglobinases, a series of inhibitors encompassing a basic 
hydroxyethylamine transition state isostere as a central fragment were prepared. 
The synthesized compounds were varied in the P1' position and exhibited 
biological activities in the range of 31 to >2000 nM. To try to rationalize the 
results, molecular docking and 3D-QSAR analysis were used.