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

A study of various 2-[(alkylsulfonyl)oxy]-6-substituted-1H-isoindole-1,3-dionesʹ inhibition of chymotrypsin compared to inhibition of HLE reveals that acylamino substitution in the 6-position increases selectivity and potency of these inhibitors for HLE. The best HLE inhibitor in this series was 6-(methylglutaryl)amino-2-[(ethylsulfonyl)oxy]-1H-isoindole-1,3-dione with a kobs/[I]=220,000 M−1 s−1.