TY - JOUR
T1 - 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
AU - Le Manach, Claire
AU - Nchinda, Aloysius T.
AU - Paquet, Tanya
AU - Gonzàlez Cabrera, Diego
AU - Younis, Yassir
AU - Han, Ze
AU - Bashyam, Sridevi
AU - Zabiulla, Mohammed
AU - Taylor, Dale
AU - Lawrence, Nina
AU - White, Karen L.
AU - Charman, Susan A.
AU - Waterson, David
AU - Witty, Michael J.
AU - Wittlin, Sergio
AU - Botha, Mariëtte E.
AU - Nondaba, Sindisiswe H.
AU - Reader, Janette
AU - Birkholtz, Lyn Marie
AU - Jiménez-Díaz, María Belén
PY - 2016/11/10
Y1 - 2016/11/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84994817362&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.6b01265
DO - 10.1021/acs.jmedchem.6b01265
M3 - Article
AN - SCOPUS:84994817362
SN - 0022-2623
VL - 59
SP - 9890
EP - 9905
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 21
ER -