2. Academic Validation
  3. Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi

Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi

  • Bioorg Med Chem. 2013 Apr 1;21(7):1756-63. doi: 10.1016/j.bmc.2013.01.050.
Martine Keenan 1,  Paul W Alexander,  Hugo Diao,  Wayne M Best,  Andrea Khong,  Maria Kerfoot,  R C Andrew Thompson,  Karen L White,  David M Shackleford,  Eileen Ryan,  Alison D Gregg,  Susan A Charman,  Thomas W von Geldern,  Ivan Scandale,  Eric Chatelain
Affiliations

Affiliation

  • 1 Epichem Pty Ltd, Murdoch University Campus, South Street, Murdoch, Western Australia 6150, Australia. martine.keenan@epichem.com.au
PMID: 23462713 DOI: 10.1016/j.bmc.2013.01.050
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.

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