Bicyclo[1.1.1]pentane

As well as being a useful isostere of the p-phenyl group, Bicyclo[1.1.1]pentane, can also be employed as an isostere of the t-butyl group. In addition, they are characterized by the shortest diagonal distance, smallest size and lowest lipophilicity due to the low number of carbon atoms. All these properties make them the most useful isostere of the p-phenyl group, especially when a simple spacer without π-stacking properties is needed. In addition, Bicyclo[1.1.1]pentanes not only retain the biological activity of the parent compounds, but they also provide enhanced properties in terms of solubility, permeability, and in vitro stability. For these reasons, the importance of this class of building blocks is expected to grow in the near future.