Novel Sulfonamide Analogs of Sivelestat as Potent Human Neutrophil Elastase Inhibitors.

ABSTRACT: Human neutrophil elastase (HNE) is involved in a number of essential physiological processes and has been identified as a potential therapeutic target for treating acute and chronic lung injury. Nevertheless, only one drug, Sivelestat, has been approved for clinical use and just in Japan and the Republic of Korea. Thus, there is an urgent need for the development of low-molecular-weight synthetic HNE inhibitors, and we have developed a wide variety of HNE inhibitors with various chemical scaffolds. We hypothesized that substitution of the active fragment of Sivelestat into these HNE inhibitor scaffolds could modulate their inhibitory activity, potentially resulting in higher efficacy and/or improved chemical stability. Here, we report the synthesis, biological evaluation, and molecular mod

SUBMITTER: Crocetti L 

PROVIDER: S-EPMC7491426 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature