ANTIMALARIAL POLYAMINE ANALOGS

被引：48
作者：
EDWARDS, ML
STEMERICK, DM
BITONTI, AJ
DUMONT, JA
MCCANN, PP
BEY, P
SJOERDSMA, A
机构：
[1] Merrell Dow Research Institute, Cincinnati
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 02期
关键词：
D O I：
10.1021/jm00106a015
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of novel tetraamines of the general formula RNH(CH2)(x)NH(CH2)(y)(NH(CH2)(x)NHR was synthesized and examined for activity against growth of Plasmodium falciparum in vitro. Within the series, dibenzyl analogues (R = benzyl) were found to be the most effective growth inhibitors, with IC50 values of about 10-6 M. Further modifications of the tetraamine provided the optimum chain length for antimalarial activity of y = 7, x = 3. Compound 8 (MDL 27,695) with the structure y = 7, x = 3, R = benzyl, in combination with the ornithine decarboxylase inhibitor alpha-(difluoromethyl)ornithine, resulted in radical cures when tested against experimental Plasmodium berghei infections in mice. The structure-activity relationships of the series are discussed.
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页码：569 / 574
页数：6
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