Reductive Breakage of the S–N Bond in <i>S</i>-Amidino Sulfenamides

In this study, reductive breakage of the S-N bond on <i>S</i>-amidino sulfenamides was examined to explore prodrug or covalent drug chemistry for thiourea compounds. Upon thiol treatment, efficient release of varying thioureas could be reached, with Pd catalysis further accelerating this process. Preliminary application to antithyroid drug methylthiouracil confirmed cysteine-triggered release of the parent drug, although further development was hampered by stability issues. These findings highlight the potential of tunable sulfenamide prodrugs to balance release kinetics and stability for thiourea therapeutics.