Our SAR investigations then focused on evaluation of fused aromatic cores (Figure ). Compounds 859 and 986, containing a benzo-fused core and a northwest aromatic moiety, were inactive, but the potency could be mitigated by fine-tuning of the substituents (e.g., p-Me (1018) or p-(NEt2) (1011)) and, interestingly, the introduction of a nitrogen atom spacer in compound 987 that was seen as promising because of the introduction of a sp 3 nitrogen providing an additional point of diversity and potentially better solubility. This compound was explored through variation of other coordinating rings in the southwest (1022, 847, 1008 and 1009) with no improvement in potency. Acylation (1021) or homologation (1019) of the amine provided no benefit, but a significant improvement in potency was seen with alkylation of the nitrogen atom (979, 981-983). While maintaining this motif, it was found that some substitutions were acceptable on the fused aromatic core (e.g., 6-methoxy in 980) though with a high degree of sensitivity to such substitutions (e.g., lower potencies seen with structurally close isomers (1001) or analogues with other minor changes (1003-1006)). While it was hoped the use of an aza-aromatic ring in the fused core might help with solubility, a nitrogen atom in any of the four available positions on that ring (i.e., 1035, 1036, 1038, 1039) was deleterious to potency. An obvious final structure to explore, 1,2disubstituted benzimidazole, was briefly explored but provided only inactive compounds (Table , Supplementary Information -Biology).