Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria

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Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria

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Title: Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria
Author: Mulrooney, Carol; Austin, Christopher P.; Beaudoin, Jennifer A.; Cheng, Ken Chih-Chien; Comer, Eamon; Dandapani, Sivaraman; Dick, Justin; Duvall, Jeremy R.; Ekland, Eric H.; Fidock, David A.; Guha, Rajarshi; Hinkson, Paul; Kramer, Martin; Masi, Daniela; Marcaurelle, Lisa A.; Su, Xin-Zhuan; Weïwer, Michel; Xia, Menghang; Yuan, Jing; Zhao, Jinghua; Palmer, Michelle; Munoz, Benito; Heidebrecht, Richard W; Barker, Robert Howard; Fitzgerald, Mark E.; Foley, Michael Raymond; Lukens, Amanda Kathleen; Thomas, Craig J.; Wiegand, Roger C.; Wirth, Dyann Fergus; Schreiber, Stuart L.

Note: Order does not necessarily reflect citation order of authors.

Citation: Heidebrecht, Richard W., Carol Mulrooney, Christopher P. Austin, Robert H. Barker, Jennifer A. Beaudoin, Ken Chih-Chien Cheng, Eamon Comer, et al. 2011. Diversity-oriented synthesis yields a novel lead for the treatment of malaria. ACS Medicinal Chemistry Letters 3(2): 112-117.
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Abstract: Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure–activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238.
Published Version: doi://10.1021/ml200244k
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276110/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11210576
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