Glycol and hydroxyphosphonate peptidomimetics as inhibitors of aspartyl proteases

The present invention relates to analogs that display selective inhibitory activity against the aspartyl proteases, plasmepsin and cathepsin D. Compounds of Formula I are disclosed as inhibitors having activity against the aspartyl proteases, plasmepsin and cathepsin D. The compounds are therefore useful for treatment of diseases such as malaria and Alzheimer's disease. In preferred compounds of Formula I, Y is an dialkoxyphosphonate, or -hydroxyamide group and Z is an acyl or -ketocarbamate functionality. Intermediates in the solid phase synthesis of compounds of Formula I, in which compounds are attached to a solid support, are also disclosed.