Settimo Luca

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  • Preprint
    Repurposing human PDE4 inhibitors for neglected tropical diseases : design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors
    ( 2014-07) Amata, Emanuele ; Bland, Nicholas D. ; Hoyt, Charles T. ; Settimo, Luca ; Campbell, Robert K. ; Pollastri, Michael P.
    A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite which causes African sleeping sickness, a neglected tropical disease that affects thousands each year, and TbrPDEB1 has been shown to be an essential target of therapeutic relevance. Noting that 1 is a weak inhibitor of TbrPDEB1, we report the design and synthesis of analogs of this compound, culminating in 12b, a sub-micromolar inhibitor of TbrPDEB1 that shows modest inhibition of T. brucei proliferation.