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ScaffoldKeys-v2.pdf (1.87 MB)

Identification of Bioisosteric Scaffolds using Scaffold Keys

preprint
revised on 20.02.2021, 18:20 and posted on 22.02.2021, 11:08 by Peter Ertl

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.


History

Email Address of Submitting Author

peter.ertl@novartis.com

Institution

Novartis Institutes for BioMedical Research

Country

Switzerland

ORCID For Submitting Author

0000-0001-6496-4448

Declaration of Conflict of Interest

none

Version Notes

version 2 (February 2021) - updated description of Scaffold Keys - updated description of the web tool - improved formatting

Exports