Author/Authors :
Fuminori Sato، نويسنده , , Yasunao Inoue، نويسنده , , Tomoki Omodani، نويسنده , , Kiyomi Imano، نويسنده , , Hiroshi Okazaki، نويسنده , , Tadashi Takemura، نويسنده , , Masanobu Komiya، نويسنده ,
Abstract :
In our search for a new agent, human neutrophil elastase (HNE) inhibitor, for the treatment of acute respiratory failure, we rationally designed and synthesized a series of peptide-based carboxylic acid-containing transition-state inhibitors. The presence of valyl moiety is found to be essential for potent in vitro inhibitory activity and also prevention of an undesirable toxicity. Of these, compound 9m has the most potent in vivo effect on HNE-induced lung hemorrhage in hamsters.
