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

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• 作者：Xianjun Liu ; Xihong Wang ; Qigui Li ; Michael P. Kozar ; Victor Melendez ; Michael T. O鈥橬eil ; Ai J. Lin
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：July 14, 2011
• 年：2011
• 卷：54
• 期：13
• 页码：4523-4535
• 全文大小：1008K
• 年卷期：v.54,no.13(July 14, 2011)
• ISSN：1520-4804

文摘

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 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.