A Developability-Focused Optimization Approach Allows Identification of in Vivo Fast-Acting Antimalarials: N-[3-[(Benzimidazol-2-yl)amino]propyl]amides

作者:Keurulainen Leena; Vahermo Mikko; Puente Felipe Margarita; Sandoval Izquierdo Elena; Crespo Fernandez Benigno; Guijarro Lopez Laura; Huertas Valentin Leticia; de las Heras Duena Laura; Leino Teppo O; Siiskonen Antti; Balla Pages Lluis; Sanz Laura M; Castaneda Casado Pablo; Belen Jimenez Diaz M; Martinez Martinez Maria S; Viera Sara; Kiuru Paula; Calderon Felix; Yli Kauhaluoma Jari*
来源:Journal of Medicinal Chemistry, 2015, 58(11): 4573-4580.
DOI:10.1021/acs.jmedchem.5b00114

摘要

Malaria continues to be a major global health problem, being particularly devastating in the African population under the age of five. Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the WHO to treat Plasmodium falciparum malaria, but clinical resistance against them has already been reported. As a consequence, novel chemotypes are urgently needed. Herein we report a novel, in vivo active, fast-acting antimalarial chemotype based on a benzimidazole core. This discovery is the result of a medicinal chemistry plan focused on improving the developability profile of an antichlamydial chemical class previously reported by our group.

  • 出版日期2015-6-11