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Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds.

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.

SUBMITTER: Jose A

PROVIDER: S-EPMC9305131 | biostudies-literature |

REPOSITORIES: biostudies-literature

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