title: Neutrophil elastase inhibitors: a patent review and potential applications for inflammatory lung diseases (2010 - 2014).
abstract: BACKGROUND
  The proteolytic activity of neutrophil elastase (NE) not only destroys pathogens but also degrades host matrix tissues by generating a localized protease-antiprotease imbalance. In humans, NE is well known to be involved in various acute and chronic inflammatory diseases, such as chronic obstructive pulmonary disease, emphysema, asthma, acute lung injury, acute respiratory distress syndrome and cystic fibrosis. The regulation of NE activity is thought to represent a promising therapeutic approach, and NE is considered as an important target for the development of novel selective inhibitors to treat these diseases.
  
  
  METHODS
  This article summarizes and analyzes patents on NE inhibitors and their therapeutic potential based on a review of patent applications disclosed between 2010 and 2014.
  
  
  CONCLUSIONS
  According to this review of recent NE inhibitor patents, all of the disclosed inhibitors can be classified into peptide- and non-peptide-based groups. The non-peptide NE inhibitors include heterocyclics, uracil derivatives and deuterium oxide. Among the heterocyclic analogs, derivatives of pyrimidinones, tetrahydropyrrolopyrimidinediones, pyrazinones, benzoxazinones and hypersulfated disaccharides were introduced. The literature has increasingly implicated NE in the pathogenesis of various diseases, of which inflammatory destructive lung diseases remain a major concern. However, only a few agents have been validated for therapeutic use in clinical settings to date.
authors.affiliation: a 1 Chang Gung University, Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine , Taoyuan 33302, Taiwan.|b 2 Chang Gung Memorial Hospital, Department of Anesthesiology , Kweishan, Taoyuan, Taiwan.
authors.forename: Yung-Fong
authors.initials: YF
authors.lastname: Tsai
authors.affiliation: a 1 Chang Gung University, Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine , Taoyuan 33302, Taiwan.|c 3 Chang Gung University, Healthy Aging Research Center, Chinese Herbal Medicine Research Team , Taoyuan 33302, Taiwan.|d 4 Chang Gung University of Science and Technology, Department of Cosmetic Science and Research Center for Industry of Human Ecology , Taoyuan 33302, Taiwan.|e 5 Chang Gung University, Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine , Taoyuan 33302, Taiwan +88 6 3211 8506 ; +88 6 3211 8506 ; htl@mail.cgu.edu.tw.
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy* / Q000503:physiopathology; D010330:Patents as Topic; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D053491:Proteinase Inhibitory Proteins, Secretory / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010455:Peptides; D053491:Proteinase Inhibitory Proteins, Secretory; D019272:Leukocyte Elastase
keywords: elastase inhibitor; inflammatory diseases; neutrophil elastase; protease–antiprotease imbalance