Structure-Guided Design and Synthesis of a Pyridazinone Series of Trypanosoma cruzi Proteasome Inhibitors
Michael G. Thomas,
Kate McGonagle,
Paul Rowland
et al.
Abstract:There is an urgent
need for new treatments for Chagas
disease,
a parasitic infection which mostly impacts South and Central America.
We previously reported on the discovery of GSK3494245/DDD01305143,
a preclinical candidate for visceral leishmaniasis which acted through
inhibition of the Leishmania proteasome. A related
analogue, active against Trypanosoma cruzi, showed suboptimal efficacy in an animal model of Chagas disease,
so alternative proteasome inhibitors were investigated. Screening
a library of pheno… Show more
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