Bicyclo[2.2.2]octane

As previously introduced, Bicyclo[2.2.2]octane is a 3D isosteres of the 2D phenyl ring, together with Bicyclo[1.1.1]pentane. Due to the presence of all sp3 carbons, Bicyclo[2.2.2]octanes can offer a number advantages over the traditional phenyl ring. The 3D structure can improve the binding site selectivity and efficiency, thus reducing toxicity and enhancing the potency of the drug. Furthermore, the lack of aromaticity could result in higher solubility. It is, however, important to keep into consideration the larger ring and increased lipophilicity of Bicyclo[2.2.2]octanes when planning to use these building blocks as phenyl isosteres.