- Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi
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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, Martine,Alexander, Paul W.,Diao, Hugo,Best, Wayne M.,Khong, Andrea,Kerfoot, Maria,Thompson, R. C. Andrew,White, Karen L.,Shackleford, David M.,Ryan, Eileen,Gregg, Alison D.,Charman, Susan A.,Von Geldern, Thomas W.,Scandale, Ivan,Chatelain, Eric
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p. 1756 - 1763
(2013/05/09)
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