A scaffold hopping exercise undertaken to expand the structural diversity of the fenarimol series of anti-Trypanosoma cruzi (T. cruzi) compounds led to preparation of simple 1-[phenyl(pyridin-3-yl)methyl]piperazinyl analogues of fenarimol which were investigated for their ability to inhibit T. cruzi in vitro in a whole organism assay. A range of compounds bearing amide, sulfonamide, carbamate/carbonate and aryl moieties exhibited low nM activities and two analogues were further studied for in vivo efficacy in a mouse model of T. cruzi infection. One compound, the citrate salt of 37, was efficacious in a mouse model of acute T. cruzi infection after once daily oral dosing at 20, 50 and 100 mg/kg for 5 days.
Keenan, M., Alexander, P. W., Diao, H., Best, W. M., Khong, A., Kerfoot, M., ... Chatelain, E. (2013). Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi
. Bioorganic & Medicinal Chemistry
(7), 1756 - 1763. https://doi.org/10.1016/j.bmc.2013.01.050