by Hawryluk N, Robinson D, Shen Y, Kyne G, Bedore M, Menon S, Canan S, von Geldern T, Townson S, Gokool S, Ehrens A, Koschel M, Lhermitte-Vallarino N, Martin C, Hoerauf A, Hernandez G, Dalvie D, Specht S, Hübner MP, Scandale I. Journal of Medicinal Chemistry 2022, 65(16);11388-11403. doi: 10.1021/acs.jmedchem.2c00960
Summary: Efforts to control and eliminate onchocerciasis are impeded by a lack of effective treatments that target the adult filarial stage. The authors previously reported a platform using surrogate nematodes in phenotypic ex vivo assays to assess activity across various parasites, which led to a series of amino-thiazole molecules demonstrating ex vivo killing of adult O. gutturosa, B. malayi, B. pahangi, and L. sigmodontis. Following on from this, in this manuscript, the authors describe the discovery of a series of substituted di(pyridin-2-yl)- 1,2,4-thiadiazol-5-amines as novel macrofilaricides for the treatment of human filarial infections.