title: Synthesis, inhibitory activity towards human leukocyte elastase and molecular modelling studies of 1-carbamoyl-4-methyleneaminoxyazetidinones.
abstract: Some monocyclic beta-lactam derivatives of type 3 (MAOAs) in which the leaving group (LG) on the C(4) is a methyleneaminoxy moiety, were synthesised and tested in vitro and in vivo for their inhibitory activity towards human leukocyte elastase (HLE). Some compounds showed an appreciable in vitro inhibitory activity against this enzyme. Effects on the anti-HLE activity due to the nature of the substituents R and R(1) present on their LG were observed and rationalised by means of molecular modelling techniques. The results of in vivo pharmacological tests indicated that MAOAs, while showing an inhibitory activity on the haemorrhage induced by HLE, did not exhibit any effects due to the R and R(1) substituents.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università degli Studi di Pisa, Via Bonanno, 6, 56100, Pisa, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Macchia
authors.forename: D
authors.initials: D
authors.lastname: Gentili
authors.forename: M
authors.initials: M
authors.lastname: Macchia
authors.forename: F
authors.initials: F
authors.lastname: Mamone
authors.forename: A
authors.initials: A
authors.lastname: Martinelli
authors.forename: E
authors.initials: E
authors.lastname: Orlandini
authors.forename: A
authors.initials: A
authors.lastname: Rossello
authors.forename: G
authors.initials: G
authors.lastname: Cercignani
authors.forename: R
authors.initials: R
authors.lastname: Pierotti
authors.forename: M
authors.initials: M
authors.lastname: Allegretti
authors.forename: C
authors.initials: C
authors.lastname: Asti
authors.forename: G
authors.initials: G
authors.lastname: Caselli
mesh_terms: D000818:Animals; D001384:Azetidines / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D010648:Phenylacetates / Q000494:pharmacology
chemical_list: D001384:Azetidines; D004791:Enzyme Inhibitors; D007769:Lactams; D010648:Phenylacetates; C083284:L 680833; D019272:Leukocyte Elastase