Current synthetic inhibitors of human neutrophil elastase in 2005

Abstract

The human neutrophil elastase (HNE)-related diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), are a serious problem worldwide. To prevent excessive production of HNE, which is a major pathogenic factor of these disorders, and to restore the appropriate balance between HNE and its inhibitors, research and development of potent synthetic HNE inhibitors has been conducted for > 30 years worldwide. At present, the following four agents can be described as the most successful: the acyl-enzyme inhibitors, ONO-5046 and MR-889, and the transition-state inhibitors, ONO-6818 and AE-3763. Additionally, protein inhibitors such as DX-890 (EPI-hNE-4), recombinant α1-antitrypsin, elafin and secretory leukocyte protease inhibitor (SLPI) are also being developed and actively researched in 2005. This review focuses upon the major synthetic HNE inhibitors, including those patented in 2004.