Cheminformatics analysis of organic substituents: identification of the most common substituents, calculation of substituent properties, and automatic identification of drug-like bioisosteric groups.

A large set of more than 3 million molecules was processed to find all the organic substituents contained in the set and to identify the most common ones. During the analysis, 849 574 unique substituents were found. Extrapolated to the number of known organic molecules, this result suggests that about 3.1 million substituents are known. Based on these findings the size of virtual organic chemistry space accessible using currently known synthetic methods is estimated to be between 10(20) and 10(24) molecules. The extracted substituents were characterized by calculated electronic, hydrophobic, steric, and hydrogen bonding properties as well as by the drug-likeness index. Various possible applications of such a large database of drug-like substituents characterized by calculated properties are discussed and illustrated by reference to a Web-based tool for automatic identification of bioisosteric groups.