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

Autor:	Mikko Vahermo, Lluís Ballell-Pages, Antti Siiskonen, Leena Keurulainen, Benigno Crespo-Fernández, Pablo Castaneda-Casado, Félix Calderón, Laura de las Heras-Dueña, Teppo O. Leino, Laura M. Sanz, Paula Kiuru, Laura Guijarro-López, Jari Yli-Kauhaluoma, Margarita Puente-Felipe, Sara Viera, Elena Sandoval-Izquierdo, Leticia Huertas-Valentin, M. Belen Jiménez-Díaz, Maria Santos Martinez-Martinez
Rok vydání:	2015
Předmět:	Models Molecular ERG1 Potassium Channel Benzimidazole Plasmodium falciparum Mice SCID Biology Pharmacology Antimalarials Structure-Activity Relationship chemistry.chemical_compound Mice Inbred NOD In vivo parasitic diseases Drug Discovery medicine Animals Humans Tissue Distribution Malaria Falciparum Artemisinin Cells Cultured Cell Proliferation Molecular Structure medicine.disease biology.organism_classification Amides Ether-A-Go-Go Potassium Channels 3. Good health African population chemistry Drug Design Benzamides Molecular Medicine Benzimidazoles Female Malaria medicine.drug
Zdroj:	Journal of Medicinal Chemistry. 58:4573-4580
ISSN:	1520-4804 0022-2623
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e926a439328a48e237daaab2d7f04e4f https://doi.org/10.1021/acs.jmedchem.5b00114 Zobrazit plný text záznamu