Synthesis and Antimalarial Activity of 2-Guanidino-4-oxoimidazoline Derivatives

被引：25

作者：

Liu, Xianjun ^{[1
]}

Wang, Xihong ^{[1
]}

Li, Qigui ^{[1
]}

Kozar, Michael P. ^{[1
]}

Melendez, Victor ^{[1
]}

O'Neil, Michael T. ^{[1
]}

Lin, Ai J. ^{[1
]}

机构：

[1] Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 13期

关键词：

TROPHOZOITE-INDUCED INFECTIONS; PLASMODIUM-FALCIPARUM MALARIA; IMIDAZOLIDINEDIONE DERIVATIVES; TAFENOQUINE; PRIMAQUINE; MEFLOQUINE; CYNOMOLGI; INVITRO; EFFICACY; MONKEYS;

D O I：

10.1021/jm200111g

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2-guanidino-4-oxoimidazoline (deoxo-IZ) derivatives was prepared and showed potent antimalarial activities in rodent and Rhesus models. Compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by Cl oral route and showed causal prophylactic activity comparable to that of the commonly used clinical drugs in Rhesus monkeys infected with sporozoites of Plasmodium cynomolgi. The metabolic stability and metabolites profile indicated that the new deoxo-IZ derivatives (8) may act as prodrugs of the corresponding IZ (1 and 2) derivatives.

引用

页码：4523 / 4535

页数：13

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