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dc.contributor.authorVarghese, Swapna
dc.contributor.authorRahmani, Raphael
dc.contributor.authorRussell, Stephanie
dc.contributor.authorDeora, Girdhar Singh
dc.contributor.authorFerrins, Lori
dc.contributor.authorToynton, Arthur
dc.contributor.authorJones, Amy
dc.contributor.authorSykes, Melissa
dc.contributor.authorKessler, Albane
dc.contributor.authorEufrasio, Amanda
dc.contributor.authorCordeiro, Artur Torres
dc.contributor.authorSherman, Julian
dc.contributor.authorRodriguez, Ana
dc.contributor.authorAvery, Vicky M
dc.contributor.authorPiggott, Matthew J
dc.contributor.authorBaell, Jonathan B
dc.date.accessioned2020-01-24T01:51:48Z
dc.date.available2020-01-24T01:51:48Z
dc.date.issued2020
dc.identifier.issn1948-5875
dc.identifier.doi10.1021/acsmedchemlett.9b00218
dc.identifier.urihttp://hdl.handle.net/10072/390858
dc.description.abstractTrypanosoma brucei (T. brucei) and Trypanosoma cruzi (T. cruzi) are causative agents of parasitic diseases known as human African trypanosomiasis and Chagas disease, respectively. Together, these diseases affect 68 million people around the world. Current treatments are unsatisfactory, frequently associated with intolerable side-effects, and generally inadequate in treating all stages of disease. In this paper, we report the discovery of N-ethylurea pyrazoles that potently and selectively inhibit the viability of T. brucei and T. cruzi. Sharp and logical SAR led to the identification of 54 as the best compound, with an in vitro IC50 of 9 nM and 16 nM against T. b. brucei and T. cruzi, respectively. Compound 54 demonstrates favorable physicochemical properties and was efficacious in a murine model of Chagas disease, leading to undetectable parasitemia within 6 days when CYP metabolism was inhibited.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Chemical Society (ACS)
dc.relation.ispartofjournalACS Medicinal Chemistry Letters
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchOrganic Chemistry
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode0304
dc.subject.fieldofresearchcode0305
dc.subject.fieldofresearchcode1115
dc.titleDiscovery of Potent N-Ethylurea Pyrazole Derivatives as Dual Inhibitors of Trypanosoma brucei and Trypanosoma cruzi
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationVarghese, S; Rahmani, R; Russell, S; Deora, GS; Ferrins, L; Toynton, A; Jones, A; Sykes, M; Kessler, A; Eufrásio, A; Cordeiro, AT; Sherman, J; Rodriguez, A; Avery, VM; Piggott, MJ; Baell, JB, Discovery of Potent N-Ethylurea Pyrazole Derivatives as Dual Inhibitors of Trypanosoma brucei and Trypanosoma cruzi, ACS Medicinal Chemistry Letters, 2019
dc.date.updated2020-01-24T01:48:40Z
gro.description.notepublicThis publication has been entered into Griffith Research Online as an Advanced Online Version.
gro.hasfulltextNo Full Text
gro.griffith.authorJones, Amy J.
gro.griffith.authorSykes, Melissa L.
gro.griffith.authorAvery, Vicky M.


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