Lead Optimization of Antimalarial Propafenone Analogues
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- 作者：David Lowes ; Anupam Pradhan ; Lalitha V. Iyer ; Toufan Parman ; Jason Gow ; Fangyi Zhu ; Anna Furimsky ; Andrew Lemoff ; W. Armand Guiguemde ; Martina Sigal ; Julie A. Clark ; Emily Wilson ; Liang Tang ; Michele C. Connelly ; Joseph L. DeRisi ; Dennis E. Kyle ; Jon Mirsalis ; R. Kiplin Guy
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：July 12, 2012
- 年：2012
- 卷：55
- 期：13
- 页码：6087-6093
- 全文大小：279K
- 年卷期：v.55,no.13(July 12, 2012)
- ISSN：1520-4804
文摘
Previously reported studies identified analogues of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are nontoxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges.