Chemical and biology of sulfur fluoride exchange (SuFEx) click chemistry for drug discovery

• Published in: Bioorganic chemistry 2023-01, Vol.130, p.106227, Article 106227
• Main Authors: Wilson Lucas, Shadrack, Zijian Qin, Richard, Rakesh, K.P., Sharath Kumar, K.S., Qin, Hua-Li
• Format: Article
• Language: English
• Subjects: Chemical and biology; Fluorine; SuFEx; Synthesis
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2022.106227

[Display omitted] •The sulfur (VI) fluoride exchange (SuFEx), is one among the most important click chemistry transformations.•Detailed explanation of structure–activity relationships (SAR) of SO2F compounds.•SF-based activity probes have become an attractive tool in chemical biology.•We have discussed application of SuFEx click chemistry in drug discovery and chemical biology. Compounds containing an SF bond have garnered intense interest in the chemical and biological literature. In particular, sulfonyl fluorides (RSO2F) are commonly used as covalent protein inhibitors and biological probes. The introduction of the fluorine atom into drugs often leads to significantly promoted medicinal properties, which revolutionized the development of pharmaceuticals and gained attention because of the beneficial properties of these small and highly electro-negative halogens. The sulfonyl fluoride functional group has also been widely adopted throughout the field of chemical biology due to its unique balance between reactivity and stability under physiological conditions. This comprehensive review highlights the recent developments of sulfonyl fluorides based compounds in a massive range of therapeutic applications. We believe this review article will be helpful to inspire new ideas for structural design and developments of less toxic and potent Sulfur based drugs against the numerous death-causing diseases.