Lead Optimization of Anti-Malarial Propafenone Analogs

Previously reported studies identified analogs 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 e...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2012-06, Vol.55 (13), p.6087-6093
Main Authors: Lowes, David, Pradhan, Anupam, Iyer, Lalitha V., Parman, Toufan, Gow, Jason, Zhu, Fangyi, Furimsky, Anna, Lemoff, Andrew, Guiguemde, W. Armand, Sigal, Martina, Clark, Julie A., Wilson, Emily, Tang, Liang, Connelly, Michele C., DeRisi, Joseph L., Kyle, Dennis E., Mirsalis, Jon, Guy, R. Kiplin
Format: Article
Language:English
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Summary:Previously reported studies identified analogs 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 non-toxic and suppress parasitemia in vivo . Although these compounds possess potential for further preclinical development, they also carry some significant challenges.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm300286a