Synthesis and applications of heterocycle-containing sulfonyl fluorides for drug discovery: a critical review.

Heterocyclic compounds represent one of the most important classes of organic molecules. It is estimated that 85% of bioactive molecules contain heterocyclic moieties. Serving as lead compounds, these active molecules have provided substantial support for the development of antimicrobial, anti-inflammatory, and antiviral drugs in human medical research. Among these, heterocycle-containing sulfonyl fluorides represent a class of promising novel compounds. Medicinal chemists have demonstrated that such molecules can play critical roles in modern pharmacology as covalent protein inhibitors, selective antibacterial agents, and [18F] imaging probes. Moreover, in recent years, heterocycle-containing sulfonyl fluoride compounds have not only achieved remarkable progress in the field of synthetic methodology, but their ability to modify amino acid residues-including tyrosine, threonine, and histidine-has also been fully exploited, thereby advancing the development of covalent therapeutics. In this review, we summarize more than 70 efficient synthetic schemes to heterocycle-containing sulfonyl fluorides, and present their latest medicinal applications to the readers. We hope this review will inspire the development of novel synthetic approaches and further biological investigations into heterocycle-containing sulfonyl fluorides.