However, as well-studied and ubiquitous as they are, these indices have a fundamental drawback, given by the fact that they can only compare two molecules at a time. This means that if we want to estimate the similarity of N compounds, we will need O(N 2 ) operations, which greatly limits the scaling of these algorithms and restricts them to narrow sections of chemical space. Motivated by these issues, a new family of similarity indices (extended or n-ary similarity indices) was recently proposed, that can compare multiple molecules at the same time. In this section we briefly review the characteristics of these indices, and some exemplary applications.