INHIBITORS OF HUMAN NEUTROPHIL ELASTASE

Human neutrophil elastase (HNE) is a serine protease that is responsib le for a number of diverse pathological conditions. Synthetic inhibito rs which can regulate the in vivo activity of HNE will therefore have broad therapeutic applications. Over the past 15 years a diverse set o f strategies have been pursued for the development of HNE inhibitors, the most successful of which have been electrophilic ketones and acyla ting agents. Many of these inhibitors have been demonstrated to preven t the deleterious effects of elastase-mediated proteolysis in a number of in vivo models. This report reviews electrophilic ketones and acyl ating agents that have appeared in the patent literature since 1993. S upporting primary literature which highlights the therapeutic potentia l of these inhibitors is also included.