When we analyze the ChEMBL database (the smallest of the databases presented in Figure ), the pyrimidine-to-imidazole and pyrimidine-to-pyrrole transformations that emerged in the analysis of the Enamine 350/3 and Mcule libraries give similarly low percentages of known compounds (0.06% and 0.32%, respectively), once again indicative of their high value. However, in this case, the pyrrole-to-pyrimidine transformation gives a remarkably small percentage of known products (0.10%). The pyridine-and pyrimidine-to-pyrrole transformations give a fewer number of known compounds in this dataset as well. Importantly, the pyrrole-to-pyrimidine conversion is the first transformation identified by this analysis that is, at least in part, reported in the chemical literature (for benzo-fused pyrroles, i.e., indoles to quinazolines). The pyrimidine-to-pyrazole transformation, which has also been reported, also gives a relatively low percentage of commercial products (0.21%) and is therefore an important transformation to add to the arsenal of methods for drug discovery. . This data is sorted for single-atom edits in Figure , and a table of the five transformations that give the lowest percentages of existing molecules (i.e., the most potentially impactful skeletal edits) is shown in Figure . This analysis reveals that the same virtual skeletal edits identified in the analyses of the other databases presented in the previous sections give the lowest percentages of existing products. For example, the pyrazole-to-furan conversion only gives 0.02% existing products. An interesting atom transmutation of a five-membered heteroaromaticthe isoxazole-to-pyrrole transformation -gives the lowest percentage of existing products out of the single-atom skeletal edits (0.34%). The same pyrimidine-to-pyrrole and pyrrole-to-pyrimidine transformations identified from the other datasets that were analyzed follow closely, giving 0.35% and 0.56% existing products, respectively. Likewise, the pyrimidine-to-pyrazole and imidazoleto-pyrimidine transformations also give low percentages of existing products.