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Cell-based optimization of novel benzamides as potential antimalarial leads |
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| Authors: | Tao Wu Advait Nagle Tomoyo Sakata Kerstin Henson Rachel Borboa Zhong Chen Kelli Kuhen David Plouffe Elizabeth Winzeler Francisco Adrian Tove Tuntland Jonathan Chang Susan Simerson Steven Howard Jared Ek John Isbell Xianming Deng Nathanael S Gray David C Tully Arnab K Chatterjee |
| Institution: | 1. Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, CA 92121, USA;2. Harvard Medical School, 250 Longwood Ave., Boston, MA 02115, USA |
| Abstract: | Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its antiplasmodial activity. The evolution of this compound series leading to optimized candidates with good cellular potency against multiple strains as well as decent in vivo profile is described in this Letter. |
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