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Discovery and structure-activity relationships of quinazolinone-2-carboxamide derivatives as novel orally efficacious antimalarials
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4646308
Author(s)
Laleu, B.; Akao, Y.; Ochida, A.; Duffy, S.; Lucantoni, L.; Shackleford, D. M.; Chen, G.; Katneni, K.; Chiu, F. C. K.; White, K. L.; Chen, X.; Sturm, A.; Dechering, K. J.; Crespo, B.; Sanz, L. M.; Wang, B.; Wittlin, S.; Charman, S. A.; Avery, V. M.; Cho, N.; Kamaura, M.
A phenotypic high-throughput screen allowed discovery of quinazolinone-2-carboxamide derivatives as a novel antimalarial scaffold. Structure-activity relationship studies led to identification of a potent inhibitor 19f, 95-fold more potent than the original hit compound, active against laboratory-resistant strains of malaria. Profiling of 19f suggested a fast in vitro killing profile. In vivo activity in a murine model of human malaria in a dose-dependent manner constitutes a concomitant benefit.
