Abstract
We report the discovery of nontoxic fungicide fenarimol as an inhibitor of Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, and the results of structure?activity investigations leading to potent analogues with low nM IC50s in a T. cruzi whole cell in vitro assay. Lead compounds suppressed blood parasitemia to virtually undetectable levels after once daily oral dosing in mouse models of T. cruzi infection. Compounds are chemically tractable, allowing rapid optimization of target biological activity and drug characteristics. Chemical and biological studies undertaken in the development of the fenarimol series toward the goal of delivering a new drug candidate for Chagas disease are reported.
Original language | English |
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Pages (from-to) | 4189 - 4204 |
Number of pages | 16 |
Journal | Journal of Medicinal Chemistry |
Volume | 55 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2012 |