New Chimeric Antimalarials with 4-Aminoquinoline Moiety Linked to a Tetraoxane Skeleton(1)

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• 作者：Igor Opsenica ; Dejan Opsenica ; Charlotte Anne Lanteri ; Lalaine Anova ; Wilbur K. Milhous ; Kirsten S. Smith ; Bogdan A. Š ; olaja
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：October 9, 2008
• 年：2008
• 卷：51
• 期：19
• 页码：6216-6219
• 全文大小：125K
• 年卷期：v.51,no.19(October 9, 2008)
• ISSN：1520-4804

文摘

The synthesis of the chimeric molecules consisting of two pharmacophores, tetraoxane and 7-chloro-4-aminoquinoline, is reported. The tetraoxanes 2, 4, and 8 show relatively potent in vitro antimalarial activities, with IC₉₀ values for the Plasmodium falciparum strain W2 of 2.26, 12.44, and 10.74 nM, respectively. In addition, two compounds, 2 and 4, cured mice in a modified Thompson test for antimalarial blood stage activity, with a minimum curative dose of 80 mg/kg, a minimum active dose of 20 mg/kg/day, and a maximum tolerated dose of >960 mg/kg.