title: Mechanism-based inhibitors of serine proteinases based on the Gabriel-Colman rearrangement.
abstract: Neutrophil-derived mediators such as, for example, the serine proteinase elastase, cathepsin G and proteinase 3, play a critical role in inflammatory lung disease. This report describes the design, synthesis and in vitro inhibitory activity of some novel mechanism-based inhibitors of human leukocyte elastase and cathepsin G. The design of the inhibitors is based on the Gabriel-Colman rearrangement. The behavior of the synthesized compounds toward elastase and cathepsin G with respect to inhibitory prowess, mode of interaction, specificity, etc., has been found to be dependent on the recognition and reactivity elements present in each inhibitor.
authors.affiliation: Department of Chemistry, Wichita State University, Kansas 67208.
authors.forename: W C
authors.initials: WC
authors.lastname: Groutas
authors.forename: L S
authors.initials: LS
authors.lastname: Chong
authors.forename: R
authors.initials: R
authors.lastname: Venkataraman
authors.forename: J B
authors.initials: JB
authors.lastname: Epp
authors.forename: R Z
authors.initials: RZ
authors.lastname: Kuang
authors.forename: M J
authors.initials: MJ
authors.lastname: Brubaker
authors.forename: N
authors.initials: N
authors.lastname: Houser-Archield
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: J J
authors.initials: JJ
authors.lastname: McClenahan
mesh_terms: D000595:Amino Acid Sequence; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases
chemical_list: D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase