Expanding the Repertoire of Low‐Molecular‐Weight Pentafluorosulfanyl‐Substituted Scaffolds. (22nd February 2022)

• Record Type: Journal Article
• Authors: Jose, Arathy; Guest, Daniel; LeGay, Remi; Tizzard, Graham J.; Coles, Simon J.; Derveni, Mariliza; Wright, Edward; Marrison, Lester; Lee, Alpha A.; Morris, Aaron; Robinson, Matt; von Delft, Frank; Fearon, Daren; Koekemoer, Lizbé; Matviuk, Tetiana; Aimon, Anthony; Schofield, Christopher J.; Malla, Tika R.; London, Nir; Greenland, Barnaby W.; Bagley, Mark C.; Spencer, John; The Covid Moonshot Consortium,
• Is Part Of: ChemMedChem. Volume 17:Number 7(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-22
• Subjects: SF5 group -- DMARDs -- COVID-19, SARS-COV-2 main protease (Mpro); Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202100641
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: The 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. Abstract : A range of molecules containing a pentafluorosulfanyl group have been made and tested versus known drug‐like entities. The SF5 functional group is of increasing interest as a bioisostere in medicinal chemistry. This library was tested against targets including human dihydroorotate dehydrogenase (HDHODH). A subsequent focused approach led to analogues of Teriflunomide and Leflunomide, considered for potential COVID‐19 treatment, where SF5 bioisostere deployment led to improved inhibition of HDHODH over the parent drugs.