Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase

Stephen Patterson, Deuan C. Jones, Emma J. Shanks, Julie A. Frearson, Ian H. Gilbert, Paul G. Wyatt, Alan H. Fairlamb

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    45 Citations (Scopus)

    Abstract

    Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP (1, 1-(1-benzo[b]thiophen-2-yl-cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (K-i = 1 mu m) and biologically active against bloodstream T brucei (EC50 = 10 mu m), but with poor selectivity against mammalian MRC5 cells (EC50 = 29 mu m). Analogues with improved enzymatic and biological activity were obtained. The structure-activity relationships of this novel series are discussed.

    Original languageEnglish
    Pages (from-to)1341-1353
    Number of pages13
    JournalChemMedChem
    Volume4
    Issue number8
    DOIs
    Publication statusPublished - Aug 2009

    Keywords

    • BTCP
    • inhibitors
    • medicinal chemistry
    • trypanosoma brucei
    • trypanothione reductase
    • DOPAMINE-UPTAKE
    • PHENCYCLIDINE-BINDING
    • TRYPANOSOMA-CRUZI
    • PCP ANALOGS
    • DERIVATIVES
    • KETONES
    • POTENT
    • 1-<1-(2-BENZO<B>THIENYL)CYCLOHEXYL>PIPERIDINE
    • METABOLISM
    • DISCOVERY

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