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ID: ALA3352078

Journal: Bioorg Med Chem Lett

Title: Repurposing human PDE4 inhibitors for neglected tropical diseases: design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors.

Authors: Amata E, Bland ND, Hoyt CT, Settimo L, Campbell RK, Pollastri MP.

Abstract: 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.

CiteXplore: 25127163

DOI: 10.1016/j.bmcl.2014.07.063