Reichenberg A, Wiesner J, Weidemeyer C, Dreiseidler E, Sanderbrand S, Altincicek B, Beck E, Schlitzer M, Jomaa H
Jomaa Pharmaka GmbH, Giessen, Germany.
Bioorg Med Chem Lett. 2001 Mar 26;11(6):833-5. doi: 10.1016/s0960-894x(01)00075-0.
The fosmidomycin derivative FR900098 represents an inhibitor of the 1-deoxy-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 i.p. drug administration.
福斯米霉素衍生物FR900098是1-脱氧-D-木酮糖5-磷酸（DOXP）还原异构酶的抑制剂，具有强大的抗疟活性。通过对膦酸酯部分进行化学修饰以生成磷酸二芳基酯，获得了口服给药后活性增强的FR900098前药。一种二芳基酯前药在感染啮齿类疟原虫文氏疟原虫的小鼠中显示出与腹腔注射给药相当的疗效。
