The 2-aminoquinazolin-4(3H)-one derivatives were designed to have linear, hydrophobic flap pocket substituents of various alkyl chain length, benzene ring position and benzene ring count (see Figure ). The initial compound subset varied in length of the linear alkyl linker between the ligand core and terminal benzene ring (2-9). Once the optimal flap pocket substituent length was identified, another ligand subset, where the substituent length was kept constant while the position of the benzene ring was varied, was synthesized (11-15). To evaluate the contribution of the terminal benzene ring on the inhibitor activity, compound 10, bearing linear alkyl chain of the same length as the most active compound was synthesized. Moreover, several compounds bearing two benzene rings at various positions were synthesized to evaluate the impact of additional benzene ring in the flap pocket substituent (16-19). For comparison purposes, compound without flap pocket substituent (1) -the original fragment hit identified in our screening campaign -was prepared and characterised as well.