A series of new boron-containing benzoxaborole compounds was designed and synthesized for a continuing structure–activity relationship (SAR) investigation to assess the antimalarial activity changes derived from side-chain structural variation, substituent modification on the benzene ring and removal of boron from five-membered oxaborole ring. This SAR study demonstrated that boron is required for the antimalarial activity, and discovered that three fluoro-substituted 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles (9, 14 and 20) have excellent potencies (IC50 0.026–0.209 µM) against Plasmodium falciparum.
Zhang YongKang; Plattner, J.J.; Freund, Y.R.; Easom, E.E.; Zhou, Y.; Long Ye; Zhou HuChen; Waterson, D.; Gamo, F.J.; Sanz, L.M.; Min Ge; Li ZhiYa; Li LingChao; Wang HaiLong; Han Cui. Benzoxaborole antimalarial agents. Part 2: Discovery of fluoro-substituted 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles. Bioorganic & Medicinal Chemistry Letters (2012) 22 (3) 1299-1307. [DOI: 10.1016/j.bmcl.2011.12.096]