Synthesis and structure–activity relationships of novel benzoxaboroles as a new class of antimalarial agents

• Published in: Bioorganic & medicinal chemistry letters 2011-01, Vol.21 (2), p.644-651
• Main Authors: Zhang, Yong-Kang, Plattner, Jacob J., Freund, Yvonne R., Easom, Eric E., Zhou, Yasheen, Gut, Jiri, Rosenthal, Philip J., Waterson, David, Gamo, Francisco-Javier, Angulo-Barturen, Inigo, Ge, Min, Li, Zhiya, Li, Lingchao, Jian, Yong, Cui, Han, Wang, Hailong, Yang, Jian
• Format: Article
• Language: English
• Subjects: Antimalarial agent; antimalarials; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Benzoxaborole; Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Boron Compounds - pharmacology; Boron-containing compound; Cell Line; Cell Survival - drug effects; Humans; Malaria, Falciparum - drug therapy; molecular weight; Parasitic Sensitivity Tests; Plasmodium falciparum; Plasmodium falciparum - drug effects; Structure-Activity Relationship; structure-activity relationships; water solubility
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.12.034

A series of boron-containing benzoxaborole compounds was designed and synthesized for a SAR investigation for discovering a new antimalarial treatment. Compound 1 demonstrates the best potency (IC 50 = 26 nM) against Plasmodium falciparum and has good drug-like properties, with low molecular weight, low ClogP and high water solubility. A series of boron-containing benzoxaborole compounds was designed and synthesized for a structure–activity relationship investigation surrounding 7-(HOOCCH 2CH 2)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole ( 1) with the goal of discovering a new antimalarial treatment. Compound 1 demonstrates the best potency (IC 50 = 26 nM) against Plasmodium falciparum and has good drug-like properties, with low molecular weight (206.00), low ClogP (0.86) and high water solubility (750 μg/mL at pH 7).