2-[(Alkylsulfonyl)oxy]-6-substituted-1H-isoindole-1,3(2H)-dione mechanism-based inhibitors of human leukocyte elastase

Derivatives of 2-[(alkylsulfonyl)oxy]-1H-isoindole-1,3(2H)-diones (N-(sulfonyloxy)phthalimides) with ring substituents in the 6-position were found to exhibit enhanced inhibitory potency and selectivity for HLE. The most potent inhibitor of HLE in this series was 6-amino-2-[(methylsulfonyl)oxy]-1H-isoindole-1,3(2H)-dione10 with a kobs/[I] of 110,000 M−1 s−1.