title: Derivatives of 3-alkyl-N-hydroxysuccinimide: probing the effect of structure on bioactivity toward human leukocyte elastase.
abstract: A structure-activity relationship study was conducted in order to probe the nature of the interaction between some 3-alkyl-N-hydroxysuccinimide derivatives and human leukocyte elastase. The structural features in substituent X (structure I) that lead to the manifestation and optimization of inhibitory activity have been examined. The data suggest that the presence of an alkyl or aryl(sulfonyloxy) group in the active compounds may serve a triple purpose, namely, it functions as a good leaving group as dictated by the established mechanism of action of this class of compounds, secondly, it may enhance binding by assuming a favorable spatial orientation and, thirdly, it may increase the chemical reactivity of the carbonyl carbon in the bioactive compounds.
authors.affiliation: Department of Chemistry, Wichita State University, Kansas 67208.
authors.forename: W C
authors.initials: WC
authors.lastname: Groutas
authors.forename: M J
authors.initials: MJ
authors.lastname: Brubaker
authors.forename: L S
authors.initials: LS
authors.lastname: Chong
authors.forename: J B
authors.initials: JB
authors.lastname: Epp
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: C E
authors.initials: CE
authors.lastname: Keller
authors.forename: J J
authors.initials: JJ
authors.lastname: McClenahan
authors.forename: R S
authors.initials: RS
authors.lastname: Givens
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: M E
authors.initials: ME
authors.lastname: Zandler
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007962:Leukocytes / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D013388:Succinimides; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase