Figure depicts the ligand core together with the different substitutions. Table shows the substitution patterns for each of the 9 ligands and the associated experimental data. In this core, 5-amides at R2 led to a more than 10-fold potency gain compared to the high-throughput screening hit, and switching then from pyrazoles to isoxazoles at X2 and adding a solubilizer group at R3 improved cellular potency by more than 3-fold.