Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi.
Basic Information
ID: ALA2331102
Journal: Bioorg Med Chem
Title: Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi.
Authors: Keenan M, Alexander PW, Diao H, Best WM, Khong A, Kerfoot M, Thompson RC, White KL, Shackleford DM, Ryan E, Gregg AD, Charman SA, von Geldern TW, Scandale I, Chatelain E.
Abstract: 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.
CiteXplore: 23462713
DOI: 10.1016/j.bmc.2013.01.050
Patent ID: ┄