2,4,5-triphenylisothiazol-3(2H)-one 1,1-dioxides as inhibitors of human leukocyte elastase

A series of substituted 2,4,5-triphenylisothiazol-3 (2 H) -one 1,1-dioxides 9 was synthesized and investigated as inhibitors of human leukocyte elastase (HLE). All compounds were found to inhibit HLE in a time-dependent manner and most of them exhibited k(obs)/[I] values > 300 M(-1)s(-1). The most potent 3-oxosultam of this series was 91 (k(obs)/[I] = 2440 M-1 s(-1)). Kinetic investigations performed with 9g and different substrate concentrations did not allow to clearly distinguish between a competitive or noncompetitive mode of inhibition. A more complex interaction is supported by the failure of a linear dependency of k(obs) values on the inhibitor concentration.