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.
|Titolo:||Repurposing human PDE4 inhibitors for neglected tropical diseases: design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors|
|Data di pubblicazione:||2014|
|Citazione:||Repurposing human PDE4 inhibitors for neglected tropical diseases: design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors / Amata, Emanuele; Bland D., Nicholas; Hoyt T., Charles; Settimo, Luca; Campbell K., Robert; Pollastri P., Michael. - In: BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS. - ISSN 1464-3405. - 24:17(2014), pp. 4084-4089.|
|Appare nelle tipologie:||1.1 Articolo in rivista|