Identification of a potential antimalarial drug candidate from a series of 2-aminopyrazines by optimization of aqueous solubility and potency across the parasite life cycle

Claire Le Manach, Aloysius T. Nchinda, Tanya Paquet, Diego Gonzàlez Cabrera, Yassir Younis, Ze Han, Sridevi Bashyam, Mohammed Zabiulla, Dale Taylor, Nina Lawrence, Karen L. White, Susan A. Charman, David Waterson, Michael J. Witty, Sergio Wittlin, Mariëtte E. Botha, Sindisiswe H. Nondaba, Janette Reader, Lyn Marie Birkholtz, María Belén Jiménez-Díaz

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46 Citations (Scopus)


Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rnull mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages.
Original languageEnglish
Pages (from-to)9890-9905
Number of pages16
JournalJournal of Medicinal Chemistry
Issue number21
Publication statusPublished - 10 Nov 2016

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