Identification of Fast-Acting 2,6-Disubstituted Imidazopyridines That Are Efficacious in the in Vivo Humanized Plasmodium falciparum NODscidIL2Rγnull Mouse Model of Malaria
dataset
posted on 2018-04-17, 00:00 authored by Aloysius
T. Nchinda, Claire Le Manach, Tanya Paquet, Diego Gonzàlez Cabrera, Kathryn J. Wicht, Christel Brunschwig, Mathew Njoroge, Efrem Abay, Dale Taylor, Nina Lawrence, Sergio Wittlin, María-Belén Jiménez-Díaz, María Santos Martínez, Santiago Ferrer, Iñigo Angulo-Barturen, Maria Jose Lafuente-Monasterio, James Duffy, Jeremy Burrows, Leslie J. Street, Kelly ChibaleOptimization of a chemical series
originating from whole-cell phenotypic
screening against the human malaria parasite, Plasmodium falciparum, led to the identification of two promising 2,6-disubstituted imidazopyridine
compounds, 43 and 74. These compounds exhibited
potent activity against asexual blood stage parasites that, together
with their in vitro absorption, distribution, metabolism, and excretion
(ADME) properties, translated to in vivo efficacy with clearance of
parasites in the PfSCID mouse model for malaria within
48 h of treatment.
