Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity

被引：84

作者：

Reichenberg, A

Wiesner, J

Weidemeyer, C

Dreiseidler, E

Sanderbrand, S

Altincicek, B

Beck, E

Schlitzer, M

Jomaa, H

机构：

[1] Jomaa Pharmala GmbH, D-35392 Giessen, Germany

[2] Univ Klin Giessen, Inst Biochem, D-35392 Giessen, Germany

[3] Univ Marburg, Inst Pharmazeut Chem, D-35032 Marburg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 06期

关键词：

D O I：

10.1016/S0960-894X(01)00075-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

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页码：833 / 835

页数：3

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