Klein, Hanna F., Hamilton, David J., de Esch, Iwan J.P. et al. (2 more authors) (2022) Escape from planarity in fragment-based drug discovery:A synthetic strategy analysis of synthetic 3D fragment libraries. Drug discovery today. pp. 2484-2496. ISSN 1359-6446
Abstract
In fragment-based drug discovery (FBDD), there is a developing appreciation that 3D fragments could offer opportunities that are not provided by 2D fragments. This review provides an overview of the synthetic strategies that have been used to prepare 3D fragments, as discussed in 25 papers published from 2011 to mid-May 2020. Three distinct strategies are highlighted: (i) diversity-oriented synthesis; (ii) the synthesis and diversification of scaffolds; and (iii) computational design and synthesis (where 3D fragments were computationally enumerated and filtered on the basis of computationally generated 3D shape descriptors and other properties). We conclude that a workflow that combines computational design and one other strategy, together with a consideration of fragment properties, 3D shape and ‘fragment sociability’, could allow 3D fragments to feature more widely in fragment libraries and could facilitate fragment-to-lead optimisation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors |
Keywords: | 3D,Fragment,Fragment-based drug discovery,Library,Synthesis |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 11 Oct 2022 15:30 |
Last Modified: | 17 Dec 2024 00:23 |
Published Version: | https://doi.org/10.1016/j.drudis.2022.05.021 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.drudis.2022.05.021 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:191985 |
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