Review Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis Inhibitors of human neutrophil elastase

Human neutrophil elastase (HNE) is a serine protease that is responsible for a number of diverse pathological conditions. Synthetic inhibitors which can regulate the in vivo activity of HNE will therefore have broad therapeutic applications. Over the past 15 years a diverse set of strategies have been pursued for the development of HNE inhibitors, the most successful of which have been electrophilic ketones and acylating agents. Many of these inhibitors have been demonstrated to prevent the deleterious effects of elastase-mediated proteolysis in a number of in vivo models. This report reviews electrophilic ketones and acylating agents that have appeared in the patent literature since 1993. Supporting primary literature which highlights the therapeutic potential of these inhibitors is also included.