Identification of Bioisosteric Scaffolds using Scaffold Keys

Replacement of a central scaffold in a bioactive molecule by another scaffold with similar structural features (a procedure called sometimes "scaffold hopping") is a classical medicinal chemistry technique used to improve molecular properties and explore novel interesting areas of chemical space. The new scaffolds may be identified by database mining, match in physicochemical properties and often just by applying medicinal chemistry knowledge. In this study a novel method to find bioisosteric scaffolds is described when these are identified using similarity in simple substructure features called Scaffold Keys. Performance of the method is illustrated on several examples and a freely-available web tool https://bit.ly/scaffoldkeys allowing to find bioisosteric scaffold analogs is introduced.