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Expanding the Repertoire of Low‐Molecular‐Weight Pentafluorosulfanyl‐Substituted Scaffolds
Author(s) -
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,
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
Publication year - 2022
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100641
Subject(s) - leflunomide , bioisostere , chemistry , dihydroorotate dehydrogenase , isoxazole , combinatorial chemistry , amide , teriflunomide , pharmacology , oxindole , stereochemistry , medicine , biochemistry , chemical synthesis , pyrimidine , in vitro , rheumatoid arthritis , multiple sclerosis , fingolimod , catalysis , psychiatry
The pentafluorosulfanyl (‐SF 5 ) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF 5 ‐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 SF 5 bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF 5 group in medicinal chemistry.