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J Med Chem. 2013 Dec 27;56(24):10158-70. doi: 10.1021/jm401610c. Epub 2013 Dec 4.

Two analogues of fenarimol show curative activity in an experimental model of Chagas disease.

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Epichem Pty Ltd. , Murdoch University Campus, South Street, Murdoch, Western Australia 6150, Australia.


Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development.

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