Lead optimization of antimalarial propafenone analogues

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 B Wilson, Liang Tang, Michele C. Connelly, Joseph L. Derisi, Dennis E. Kyle, Jon Mirsalis, R. Kiplin Guy

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6087-6093
Number of pages7
JournalJournal of Medicinal Chemistry
Volume55
Issue number13
DOIs
StatePublished - Jul 12 2012
Externally publishedYes

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Propafenone
Parasitemia
Antimalarials
Ion Channels
Toxicology
Biological Availability
Malaria
Rodentia
Pharmacokinetics
Lead

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Lowes, D., Pradhan, A., Iyer, L. V., Parman, T., Gow, J., Zhu, F., ... Guy, R. K. (2012). Lead optimization of antimalarial propafenone analogues. Journal of Medicinal Chemistry, 55(13), 6087-6093. https://doi.org/10.1021/jm300286a

Lead optimization of antimalarial propafenone analogues. / 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 B; Tang, Liang; Connelly, Michele C.; Derisi, Joseph L.; Kyle, Dennis E.; Mirsalis, Jon; Guy, R. Kiplin.

In: Journal of Medicinal Chemistry, Vol. 55, No. 13, 12.07.2012, p. 6087-6093.

Research output: Contribution to journalArticle

Lowes, D, Pradhan, A, Iyer, LV, Parman, T, Gow, J, Zhu, F, Furimsky, A, Lemoff, A, Guiguemde, WA, Sigal, M, Clark, JA, Wilson, EB, Tang, L, Connelly, MC, Derisi, JL, Kyle, DE, Mirsalis, J & Guy, RK 2012, 'Lead optimization of antimalarial propafenone analogues', Journal of Medicinal Chemistry, vol. 55, no. 13, pp. 6087-6093. https://doi.org/10.1021/jm300286a
Lowes D, Pradhan A, Iyer LV, Parman T, Gow J, Zhu F et al. Lead optimization of antimalarial propafenone analogues. Journal of Medicinal Chemistry. 2012 Jul 12;55(13):6087-6093. https://doi.org/10.1021/jm300286a
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 B ; Tang, Liang ; Connelly, Michele C. ; Derisi, Joseph L. ; Kyle, Dennis E. ; Mirsalis, Jon ; Guy, R. Kiplin. / Lead optimization of antimalarial propafenone analogues. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 13. pp. 6087-6093.
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