Important to mention that the acidity of aromatic carboxylic acid 61 and 2-oxabicyclo[2.2.2]octane 37 were almost identical (Figure ). Indeed, the replacement of the phenyl ring in acid 61 with the bicyclo[2.2.2]octane core reduced the acidity: pKa=4.5 (61) vs 5.6 (62). However, incorporation of the β-oxygen atom into the latter ideally restored it: pKa=4.4 (37). Because the acidity/basicity of functional groups is often responsible for the potency, selectivity, and toxicity of bioactive compounds, the fine-tuning of the pKa by replacing the phenyl ring with isomeric 2-oxabicyclo[2.2.2]octanes could be a solution here. Incorporation into bioactive compound. To demonstrate the practical utility of the 2-oxabicyclo[2.2.2]octane scaffold, we incorporated it into the structure of the anticancer drug Imatinib, instead of the phenyl ring (Scheme 6). The reaction of iodide 45 with N-methyl piperazine, followed by acylation with the substituted aniline gave compound 63a saturated analogue of Imatinib. For comparison, we also synthesized compound 64 with bicyclo[2.2.2]octane core (please, see SI for details). The commercialized drug Imatinib is used in practice as a mesylate salt. However, to estimate the impact of the replacement of the phenyl ring with bioisosteres on the physicochemical properties, we prepared and studied all three compounds, -63, 64, Imatinib, -as free bases.