TY - JOUR
T1 - A Developability-Focused Optimization Approach Allows Identification of in Vivo Fast-Acting Antimalarials
T2 - N-[3-[(Benzimidazol-2-yl)amino]propyl]amides
AU - Keurulainen, Leena
AU - Vahermo, Mikko
AU - Puente-Felipe, Margarita
AU - Sandoval-Izquierdo, Elena
AU - Crespo-Fernandez, Benigno
AU - Guijarro-Lopez, Laura
AU - Huertas-Valentin, Leticia
AU - de las Heras-Duena, Laura
AU - Leino, Teppo O.
AU - Siiskonen, Antti
AU - Balla-Pages, Lluis
AU - Sanz, Laura M.
AU - Castaneda-Casado, Pablo
AU - Belen Jimenez-Diaz, M.
AU - Martinez-Martinez, Maria S.
AU - Viera, Sara
AU - Kiuru, Paula
AU - Calderon, Felix
AU - Yli-Kauhaluoma, Jari
PY - 2015/6/11
Y1 - 2015/6/11
N2 - 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.
AB - 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.
KW - PLASMODIUM-FALCIPARUM
KW - STARTING POINTS
KW - DE-POINTES
KW - MALARIA
KW - BENZIMIDAZOLES
KW - PROLONGATION
KW - TCAMS
U2 - 10.1021/acs.jmedchem.5b00114
DO - 10.1021/acs.jmedchem.5b00114
M3 - Article
SN - 0022-2623
VL - 58
SP - 4573
EP - 4580
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 11
ER -
