ChemMedChem - 2022 - Jose - Expanding the Repertoire of LowMolecularWeight PentafluorosulfanylSubstituted Scaffolds.pdf (5.13 MB)
Expanding the repertoire of low-molecular-weight pentafluorosulfanyl-substituted scaffolds
journal contribution
posted on 2023-06-10, 02:42 authored by Arathy Jose, Daniel GuestDaniel Guest, Remi LeGay, Graham J Tizzard, Simon J Coles, Maria Derveni, Edward WrightEdward Wright, Lester Marrison, Alpha A Lee, Aaron Morris, Matt Robinson, Frank Delft, Daren Fearon, Lizbé Koekemoer, Tetiana Matviuk, Anthony Aimon, Christopher J Schofield, Tika R Malla, Nir London, Barnaby GreenlandBarnaby Greenland, Mark BagleyMark Bagley, John SpencerJohn Spencer, The Covid Moonshot ConsortiumThe pentafluorosulfanyl (-SF5) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF5-containing compounds, including amide, isoxazole, and oxindole derivatives, was synthesised using a range of solution-based and solventless methods, including microwave and ball-mill techniques. The library was tested against targets including human dihydroorotate dehydrogenase (HDHODH). A subsequent focused approach led to synthesis of analogues of the clinically used disease modifying anti-rheumatic drugs (DMARDs), Teriflunomide and Leflunomide, considered for potential COVID-19 use, where SF5 bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF5 group in medicinal chemistry.
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- Published
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- Published version
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ChemMedChemISSN
1860-7179Publisher
WileyExternal DOI
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1-12Article number
a202100641Department affiliated with
- Chemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-02-23First Open Access (FOA) Date
2022-02-23First Compliant Deposit (FCD) Date
2022-02-22Usage metrics
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