ArticleFrontiers in chemistry2020
Novel Sulfonamide Analogs of Sivelestat as Potent Human Neutrophil Elastase Inhibitors.
Article in Frontiers in chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- The Differential Redox Resilience of Alvelestat and Sivelestat: A Mechanistic Hypothesis for Inhibitor Performance Under Oxidative Stress.Molecules (Basel, Switzerland) · 2026Article
- Human Neutrophil Elastase and the Protein-Storm Axis: Reversible Synthetic Inhibitors in Inflammatory Disease.Molecules (Basel, Switzerland) · 2026Review
- Efficacy of sivelestat in alleviating postoperative pulmonary injury in patients with acute aortic dissection undergoing total arch replacement: a retrospective cohort study.BMC cardiovascular disorders · 2025Article
- Effect of sivelestat on postoperative outcomes in patients with acute type A aortic dissection and hypoxemia: a retrospective analysis.American journal of cardiovascular disease · 2025Article
- Discovery of Pyrazoline Benzenesulfonamide Derivatives as Anticancer Agents: A Review.Drug design, development and therapy · 2025Review
- The Multifaceted Role of Neutrophils in NSCLC in the Era of Immune Checkpoint Inhibitors.Cancers · 2024Review
- Ebselen analogues with dual human neutrophil elastase (HNE) inhibitory and antiradical activity.RSC medicinal chemistry · 2024Article
- Discovery of New 3,3-Diethylazetidine-2,4-dione Based Thiazoles as Nanomolar Human Neutrophil Elastase Inhibitors with Broad-Spectrum Antiproliferative Activity.International journal of molecular sciences · 2022Article
- 1,5,6,7-Tetrahydro-4H-indazol-4-ones as human neutrophil elastase (HNE) inhibitors.Bioorganic & medicinal chemistry letters · 2021Article
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Authors and funding
8 authors.
Funding
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 modeling studies of novel compounds substituted with the 4-(sulfamoyl)phenyl pivalate fragment necessary for Sivelestat activity. Many of these compounds were potent HNE inhibitors with activity in the nanomolar range (IC
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