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

Martine Keenan, Paul W Alexander, Hugo Diao, Wayne Morris Best, Andrea Khong, Maria Kerfoot, Richard Christopher Andrew Thompson, Karen Louise White, David Shackleford, Eileen Ryan, Alison Dianne Gregg, Susan Ann Charman, Thomas W von Geldern, Ivan Scandale, Eric Chatelain

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20 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1756 - 1763
Number of pages8
JournalBioorganic & Medicinal Chemistry
Volume21
Issue number7
DOIs
Publication statusPublished - 2013

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