Lead optimization of antimalarial propafenone analoguesLowes D, Pradhan A, Iyer LV, Parman T, Gow J, Zhu F, Furimsky A, Lemoff A, Guiguemde WA, Sigal M, Clark JA, Wilson E, Tang L, Connelly MC, Derisi JL, Kyle DE, Mirsalis J, Guy RK
J Med Chem, 2012Abstract: 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
