Selective chlorination of iminosydnones for fast release of amide, sulfonamide and urea-containing drugs

Herein, we describe a methodology for iminosydnone chlorination and we demonstrate the high beneficial effect of this modification on the reactivity of these mesoionic dipoles in strain-promoted cycloaddition reactions. Exploiting their reaction with cyclooctynes, we used these new iminosydnones for bioorthogonal release of amide, urea and sulfonamide containing drugs. Notably, drugs containing a terminal amide function were released for the first time with good kinetic constants.

Automated summary

In this study, a methodology for chlorination of iminosydnones is described, and the beneficial effect of this modification on the reactivity of these mesoionic dipoles in strain-promoted cycloaddition reactions is demonstrated. The new iminosydnones are used for bioorthogonal release of drugs containing amide, urea, and sulfonamide, with notable success in releasing drugs containing a terminal amide function.