Furthermore, the positioning of the 3,4-dichlorophenyl tail of 1a in subpocket D of necting a 3,4-dichlorophenyl moiety with various linkers. A virtual compound library was constructed and evaluated by docking simulations and ADMET property predictions, leading to the synthesis of 12 compounds. Among these, 1a and 1b emerged as potent inhibitors of TbPTR1, with 1b also showing a micromolar inhibition level against LmPTR1 and moderate activity against L. infantum (close to 50% at 10 µM), demonstrating its potential as a dual-PTR1 inhibitor, which is rather unusual for 2-aminobenzothiazole derivatives . In addition, these compounds were less toxic for THP-1 cells than the reference compound I (Tab. 2), and had an overall toxicity profile comparable to the previously synthesized 2aminobenzothiazole derivatives (Tab. S4 in SI and ref. 22). The compound most active against T. brucei, 1a, achieved a selectivity of 16 against THP-1 cells.