title: Pseudosaccharin amine derivatives: synthesis and elastase inhibitory activity.
abstract: Pseudosaccharin amines were synthesized from saccharin either by the reaction of pseudosaccharin chloride with amines, or via thiosaccharin which was treated with amines yielding thiosaccharinates, and their reaction with glacial acetic acid. This route gave lower yields than the first way. The synthesis of alkyl [(1,1-dioxo-benzo[d]isothiazol-3-yl)amino]alkanoates as possible Human Leukocyte Elastase (HLE) inhibitors was realized by the reaction between amino acid esters and pseudosaccharin chloride. Hydrolysis of the esters was possible under aqueous basic conditions. Selected compounds were screened for elastase inhibitory activity. Compounds 4k and 4m were found to be reversible inhibitors of HLE with Ki values of 45 microM and 60 microM.
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: H B
authors.initials: HB
authors.lastname: Rode
authors.forename: T
authors.initials: T
authors.lastname: Sprang
authors.forename: A
authors.initials: A
authors.lastname: Besch
authors.forename: J
authors.initials: J
authors.lastname: Loose
authors.forename: H H
authors.initials: HH
authors.lastname: Otto
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000588:Amines; D007202:Indicators and Reagents; D011480:Protease Inhibitors; D013844:Thiazoles; D010196:Pancreatic Elastase