The enormous sized "drug-like" chemical space is frequently discussed. One estimation based on the GDB-17 data set is that the chemical space contains 10 33 compounds . There is no broadly accepted way to quantify how much of this vast space is similar to a given compound of interest, in other words how dense is the chemical space. Further, although there exist methods that allow for local combinatorial modification of compounds based on reagents and based on matched molecular pairs (MMP) , despite the key practical importance of this task, no existing method is currently available that can systematically and exhaustively sample this bespoke chemical space.