Keurulainen Leena, Vahermo Mikko, Puente-Felipe Margarita, Sandoval-Izquierdo Elena, Crespo-Fernández Benigno, Guijarro-López Laura, Huertas-Valentín Leticia, de las Heras-Dueña Laura, Leino Teppo O, Siiskonen Antti, Ballell-Pages Lluís, Sanz Laura M, Castañeda-Casado Pablo, Jiménez-Díaz M Belén, Martínez-Martínez María S, Viera Sara, Kiuru Paula, Calderón Félix, Yli-Kauhaluoma Jari
†Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Viikinkaari 5 E (P.O. Box 56), FI-00014 Helsinki, Finland.
‡Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain.
J Med Chem. 2015 Jun 11;58(11):4573-80. doi: 10.1021/acs.jmedchem.5b00114. Epub 2015 May 19.
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.
疟疾仍然是一个重大的全球健康问题，对五岁以下的非洲人口尤其具有毁灭性。以青蒿素为基础的联合疗法（ACTs）是世界卫生组织推荐用于治疗恶性疟原虫疟疾的一线治疗方法，但已经有针对它们的临床耐药性报道。因此，迫切需要新型化学类型。在此，我们报告了一种基于苯并咪唑核心的新型、体内有活性、速效抗疟化学类型。这一发现是一项药物化学计划的成果，该计划专注于改善我们小组先前报道的一类抗衣原体化学物质的可开发性。
