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

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• 作者：Leena Keurulainen ; Mikko Vahermo ; Margarita Puente-Felipe ; Elena Sandoval-Izquierdo ; Benigno Crespo-Fern谩ndez ; Laura Guijarro-L贸pez ; Leticia Huertas-Valent铆n ; Laura de las Heras-Due帽a ; Teppo O. Leino ; Antti Siiskonen ; Llu铆s Ballell-Pages ; Laura M. Sanz ; Pablo Casta帽eda-Casado ; M. Bel茅n Jim茅nez-D铆az ; Mar铆a S. Mart铆nez-Mart铆nez ; Sara Viera ; Paula Kiuru ; F茅lix Calder贸n ; Jari Yli-Kauhaluoma
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：June 11, 2015
• 年：2015
• 卷：58
• 期：11
• 页码：4573-4580
• 全文大小：486K
• ISSN：1520-4804

文摘

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.