Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity

The fosmidomycin derivative FR900098 represents an inhibitor of the 1deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase with potent antimalarial activity. Prodrugs of FR900098 with increased activity after oral administration were obtained by chemical modification of the phosphonate moiety to yield phosphodiaryl esters. One diaryl ester prodrug demonstrated efficacy in mice infected with the rodent malaria parasite Plasmodium vinckei comparable to ip drug administration. (C) 2001 Elsevier Science Ltd. All rights reserved.