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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. 29 — Key stages in the hit to lead pathway of KAE609. Resolution of the initial racemic hit (K′1) gave the significantly more potent stereoisomer (K′2). Reducing the ring size further increased the potency and final halogenation of the indole ring led to the optimized compound KAE609