Identification of Bioisosteric Scaffolds using Scaffold Keys

22 February 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.


Keywords

scaffolds
scaffold keys
bioisosteric design
chemical space
naive Bayes classifier
cheminformatics
web tools

Supplementary weblinks

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.