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. 2019 Mar 22;18:93. doi: 10.1186/s12936-019-2724-z

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© The Author(s) 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Fig. 33 — Key stages in the hit to lead pathway of MMV048. Initial replacement of the 3-methoxy-4-hydroxyphenyl moiety helped to improve in vivo stability and solubility. Further replacement of the methoxy group with a trifluoromethyl group improved potency and metabolic stability leading to the optimized compound