Our first spirocycles were originally thought of as isosteres of more common rings (morpholine -> spiromorpholines, piperazine -> spiropiperazines etc.) to be used classical medicinal chemistry programs such as Structure-Activity Relationship studies, ADME optimization.
But they were also demonstrated to be very useful for scaffold-hopping strategies. Many of our scaffolds bring an extra degree of rigidity that can be useful to reduce the entropy. We have seen data showing that classical scaffolds bearing exit vectors can be replaced by spirocyclic cores. And if the overlap is not perfect, it should not stop you! Because of the nature of spirocycles, it is possible to fine-tune their geometrical properties to access almost any possible set of dihedral angles and distance between each exit vector, simply by playing with the size of each ring and their substitution pattern. And this can be done in every direction! Spirocycles are three-dimensional scaffolds!!!