In the present study, we focused on developing a series of compounds bearing a 3,4dichlorophenyl moiety, a key component of potent TbPTR1 inhibitors designed by Mpamhanga et al. , including, e.g., 1-(3,4-dichlorobenzyl)-1H-benzimidazol-2-amine (I, Fig. , Tab. 1, see also Fig. in SI). These inhibitors displayed up to nanomolar activity against TbPTR1 and about 10-micromolar activity against the parasite. The compounds were found to bind to non-substrate subpockets C and D of TbPTR1 (as defined in ref. 25), where the 3,4-dichlorophenyl moiety is positioned in subpocket C (see Fig. ). In a subsequent study, the 3,4-dichlorophenyl moiety was incorporated into the structures of several 2aminobenzothiazole derivatives , e.g., in V (Fig. ), which was the best TbPTR1 in- a Original codes for the previously published reference compounds: I is 9 from Mpamhanga et al. ; II-VII correspond to 1d, 2d, 3d, 4d, 4r, 4t from Linciano et al . Chemical structures of additional reference compounds VIII-X are in Fig. (SI).