Acyloxyalkyl ester Prodrugs of FR900098 with improved in vivo anti-malarial activity

被引：70

作者：

Ortmann, R

Wiesner, J

Reichenberg, A

Henschker, D

Beck, E

Jomaa, H

Schlitzer, M

机构：

[1] Univ Munich, Dept Pharm, D-81377 Munich, Germany

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 13期

关键词：

D O I：

10.1016/S0960-894X(03)00354-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

FR900098 represents an improved derivative of the new antimalarial drug fosmidomycin and acts through inhibition of the 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, an essential enzyme of the mevalonate independent pathway of isoprenoid biosynthesis. Prodrugs with increased activity after oral administration were obtained by chemical modification of the phosphonate moiety to yield acyloxyalkyl esters. The most successful compound demonstrated 2-fold increased activity in mice infected with the rodent malaria parasite Plasmodium vinckei. (C) 2003 Elsevier Science Ltd. All rights reserved.

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页码：2163 / 2166

页数：4

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