Design, structure–activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi
Keenan, M., Alexander, P.W., Diao, H., Best, W.M., Khong, A., Kerfoot, M., Thompson, R.C.A., White, K.L., Shackleford, D.M., Ryan, E., Gregg, A.D., Charman, S.A., von Geldern, T.W., Scandale, I. and Chatelain, E. (2013) Design, structure–activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi. Bioorganic & Medicinal Chemistry Letters, 21 (7). pp. 1756-1763.
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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.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||School of Veterinary and Life Sciences|
|Copyright:||© 2013 Elsevier Ltd.|
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