We hypothesised that introducing a carboxylic acid group onto one of the active-site binding fragments (21, Table ) would increase binding affinity. This was indeed the case for the ligands 122-124 (Table , Figure ). These ligands have KD values in the sub-millimolar to mid-micromolar range and LEs of > 0.30 kcal/mol/ heavy atom. Thus, they are promising starting points for further optimization. The imidazole analogue 118 has a KD of 480 µM while no affinity could be determined for the screening hit 21 containing a pyrrole. Therefore, a viable next step to further increase affinity in this series appears to be to investigate imidazole analogues.