The Chan-Lam-type synthesis of thioimidazolium salts for thiol-(hetero)arene conjugation

The design of stable and variable aryl linkers for conjugating drug moieties to the metabolism-related thiols is of importance in drug discovery, especially in the field of antibody-drug conjugates (ADCs). We disclosed that thioimidazolium groups are unique scaffolds for the thiol-(hetero)arene conjugation under mild conditions. The drug bound thioimidazolium salts, which are easily accessible via a copper-mediated Chan-Lam process in gram-scale, could be successfully applied to the late-stage coupling of bioactive thiols to construct a broad array of drug-like molecules.