Identification of Fast-Acting 2,6-Disubstituted Imidazopyridines That Are Efficacious in the in Vivo Humanized Plasmodium falciparum NODscidIL2Rγ null Mouse Model of Malaria

作者：Aloysius T. Nchinda, Claire Le Manach, Tanya Paquet, Diego González Cabrera, Kathryn J. Wicht, Christel Brunschwig, Mathew Njoroge, Efrem Abay, Dale Taylor, Nina Lawrence, Sergio Wittlin, María-Belén Jiménez-Díaz, Maria Santos Martínez, Santiago Ferrer, Íñigo Angulo‐Barturen, María José Lafuente-Monasterio, James Duffy, Jeremy N. Burrows, Leslie J. Street, Kelly Chibale · 发表于：Journal of Medicinal Chemistry · 年份：2018 · DOI：10.1021/acs.jmedchem.8b00382 · 被引用次数：20 · 研究领域：Malaria Research and Control、Synthesis and Catalytic Reactions、Phenothiazines and Benzothiazines Synthesis and Activities

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.