This class of molecules did display reduced solubility in aqueous media, thus, we first assessed thermodynamic solubility experimentally for the four prioritized analogs using a method previously described. This analysis showed 38 was the most soluble at 33.6 µM in PBS at pH 7.4 and 25 °C, which is approximately 60-fold higher than the cellular IC50 for inhibition of Ca2+/Calmodulin-stimulated AC1 activity. This was followed by 16 (19.5 µM), 20 (10.8 µM) and 39 (7.6 µM) in decreasing order of solubility (Table ).