Enabling synthesis in fragment-based drug discovery by reactivity mapping: photoredox-mediated cross-dehydrogenative heteroarylation of cyclic amines

Rachel Grainger; Tom D. Heightman; Steven V. Ley; Fabio Lima; Christopher N. Johnson

doi:10.1039/c8sc04789h

Enabling synthesis in fragment-based drug discovery by reactivity mapping: photoredox-mediated cross-dehydrogenative heteroarylation of cyclic amines

Chemical Science ◽

10.1039/c8sc04789h ◽

2019 ◽

Vol 10 (8) ◽

pp. 2264-2271 ◽

Cited By ~ 20

Author(s):

Rachel Grainger ◽

Tom D. Heightman ◽

Steven V. Ley ◽

Fabio Lima ◽

Christopher N. Johnson

Keyword(s):

Drug Discovery ◽

Cyclic Amines ◽

Dehydrogenative Coupling ◽

Direct Cross ◽

Fragment Based Drug Discovery ◽

Synthetic Transformations

A nanogram-to-gram workflow has been established for the identification and development of synthetic transformations which are enabling in Fragment-Based Drug Discovery (FBDD). In this study, we disclose a method for the synthesis of privileged sp2–sp3 architectures via direct cross-dehydrogenative coupling of heterocycles.

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Faculty Opinions recommendation of An NMR Biochemical Assay for Fragment-Based Drug Discovery: Evaluation of an Inhibitor Activity on Spermidine Synthase of Trypanosoma cruzi.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726180549.793515078 ◽

2016 ◽

Author(s):

Robert Powers ◽

Fatema Bhinderwala

Keyword(s):

Drug Discovery ◽

Trypanosoma Cruzi ◽

Biochemical Assay ◽

Spermidine Synthase ◽

Inhibitor Activity ◽

Fragment Based Drug Discovery

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Faculty Opinions recommendation of Design Principles for Fragment Libraries: Maximizing the Value of Learnings from Pharma Fragment-Based Drug Discovery (FBDD) Programs for Use in Academia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726318916.793517848 ◽

2016 ◽

Author(s):

John Lowe

Keyword(s):

Drug Discovery ◽

Design Principles ◽

Fragment Libraries ◽

Fragment Based Drug Discovery

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What makes a good fragment in fragment-based drug discovery?

Expert Opinion on Drug Discovery ◽

10.1080/17460441.2021.1905629 ◽

2021 ◽

pp. 1-4

Author(s):

Zenon Konteatis

Keyword(s):

Drug Discovery ◽

Fragment Based Drug Discovery

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Binding thermodynamics discriminates fragments from druglike compounds: a thermodynamic description of fragment-based drug discovery

Drug Discovery Today ◽

10.1016/j.drudis.2016.11.019 ◽

2017 ◽

Vol 22 (4) ◽

pp. 681-689 ◽

Cited By ~ 13

Author(s):

Glyn Williams ◽

György G. Ferenczy ◽

Johan Ulander ◽

György M. Keserű

Keyword(s):

Drug Discovery ◽

Thermodynamic Description ◽

Binding Thermodynamics ◽

Fragment Based Drug Discovery

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Validating Fragment-Based Drug Discovery for Biological RNAs: Lead Fragments Bind and Remodel the TPP Riboswitch Specifically

Chemistry & Biology ◽

10.1016/j.chembiol.2014.03.007 ◽

2014 ◽

Vol 21 (5) ◽

pp. 591-595 ◽

Cited By ~ 43

Author(s):

Katherine Deigan Warner ◽

Philip Homan ◽

Kevin M. Weeks ◽

Alison G. Smith ◽

Chris Abell ◽

...

Keyword(s):

Drug Discovery ◽

Fragment Based Drug Discovery

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Escape from planarity in fragment-based drug discovery: A physicochemical and 3D property analysis of synthetic 3D fragment libraries

Drug Discovery Today Technologies ◽

10.1016/j.ddtec.2021.05.001 ◽

2021 ◽

Author(s):

David J. Hamilton ◽

Tom Dekker ◽

Hanna F. Klein ◽

Guido V. Janssen ◽

Maikel Wijtmans ◽

...

Keyword(s):

Drug Discovery ◽

Property Analysis ◽

Fragment Libraries ◽

Fragment Based Drug Discovery

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Screening and identification of Lassa virus endonuclease-targeting inhibitors from a fragment-based drug discovery library

Antiviral Research ◽

10.1016/j.antiviral.2021.105230 ◽

2021 ◽

pp. 105230

Author(s):

Xiaohao Lan ◽

Yueli Zhang ◽

Xiaoying Jia ◽

Siqi Dong ◽

Yang Liu ◽

...

Keyword(s):

Drug Discovery ◽

Lassa Virus ◽

Screening And Identification ◽

Fragment Based Drug Discovery

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Fragment Library of Natural Products and Compound Databases for Drug Discovery

Biomolecules ◽

10.3390/biom10111518 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1518 ◽

Cited By ~ 1

Author(s):

Ana L. Chávez-Hernández ◽

Norberto Sánchez-Cruz ◽

José L. Medina-Franco

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Synthetic Compounds ◽

Drug Candidates ◽

Compound Libraries ◽

Chemical Database ◽

Fragment Library ◽

Further Development ◽

Fragment Libraries ◽

Fragment Based Drug Discovery

Natural products and semi-synthetic compounds continue to be a significant source of drug candidates for a broad range of diseases, including coronavirus disease 2019 (COVID-19), which is causing the current pandemic. Besides being attractive sources of bioactive compounds for further development or optimization, natural products are excellent substrates of unique substructures for fragment-based drug discovery. To this end, fragment libraries should be incorporated into automated drug design pipelines. However, public fragment libraries based on extensive collections of natural products are still limited. Herein, we report the generation and analysis of a fragment library of natural products derived from a database with more than 400,000 compounds. We also report fragment libraries of a large food chemical database and other compound datasets of interest in drug discovery, including compound libraries relevant for COVID-19 drug discovery. The fragment libraries were characterized in terms of content and diversity.

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