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This compound had previously been identified as a potent and selective antiplasmodial agent, where a focused optimization campaign, resulted in a medium\u2010sized library of compounds, with favorable drug\u2010like properties, one of which (MMV048, <jats:bold>2<\/jats:bold>, 5\u2010(4\u2010(methylsulfonyl)phenyl)\u20106\u2032\u2010(trifluoromethyl)\u2010[3,3\u2032\u2010bipyridin]\u20102\u2010amine) is currently undergoing clinical trials for malaria. Accordingly, we investigated this library, in order to elucidate structural activity relationship details of this class of compounds as inhibitors of <jats:italic>Trypanosoma brucei<\/jats:italic>. Our study has identified several structural features important for antitrypanosomal activity, which are distinct from those required for antiplasmodial activity. Results from this study can be exploited to develop potent antitrypanosomal agents.<\/jats:p>","DOI":"10.1002\/cmdc.201900492","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T07:56:53Z","timestamp":1572508613000},"page":"2034-2041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exploring the Antiplasmodial 2\u2010Aminopyridines as Potential Antitrypanosomal Agents"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4043-7106","authenticated-orcid":false,"given":"Clinton G. 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