jm8b00382_si_003.xlsx (13.52 kB)
Identification of Fast-Acting 2,6-Disubstituted Imidazopyridines That Are Efficacious in the in Vivo Humanized Plasmodium falciparum NODscidIL2Rγnull Mouse Model of Malaria
datasetposted 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 Chibale
Optimization 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.