All cheminformatics analysis was carried out using RDKit version 2023.09.5, unless otherwise stated. retain information about the presence and location of sp 2 hybridized groups, such as the carbonyl. However, in the current case the generic Murcko scaffold is necessary to obtain SCINS which disregards topology. Therefore, we argue that an additional chain in the generic scaffold resulting from the carbonyl group would just add noise to the already very coarse SCINS descriptor. One caveat with our approach is that compounds containing atoms with valence higher than 4 (such as the sulfur in Aryl-SF5) would fail the first step (as this would result in a hexavalent carbon, which raises an error in RDKit upon sanitization). This could be avoided by changing the code that obtains the scaffold to also remove carbonyl and similar groups. We provide such a function in the SCINS package but do not use it in this work as in our experience it is slower by about 30% compared to the C++ implementation in RDKit.