Thus, the structural and biochemical data show that both subpockets C and D can be occupied by a 3,4-dichlorophenyl moiety in potent TbPTR1 inhibitors, and that their activity may be modulated by altering their scaffolds. This prompted us to investigate the structureactivity relationship (SAR) associated with targeting these subpockets in a FBDD approach to design new 2-aminobenzothiazole derivatives.