A series of 6-hetaryloxy benzoxaborolecompounds was designed andsynthesized for a structure–activity relationship (SAR) investigationto assess the changes in antimalarial activity which result from 6-aryloxystructural variation, substituent modification on the pyrazine ring,and optimization of the side chain ester group. This SAR study discoveredhighly potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles(9, 27–34) with IC50s = 0.2–22 nM against cultured PlasmodiumfalciparumW2 and 3D7 strains. Compound 9also demonstrated excellent in vivo efficacy against P. bergheiin infected mice (ED90= 7.0mg/kg). [ABSTRACT FROM AUTHOR]