Synthesis, inhibitory activity towards human leukocyte elastase and molecular modelling studies of 1-carbamoyl-4-methyleneaminoxyazetidinones

Some monocyclic beta-lactam derivatives of type 3 (MAOAs) in which the leav ing group (LG) on the C(4) is a methyleneaminoxy moiety, were synthesised a nd tested in vitro and in vivo for their inhibitory activity towards human leukocyte elastase (HLE). Some compounds showed an appreciable in vitro inh ibitory 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 observ ed and rationalised by means of molecular modelling techniques. The results of in vivo pharmacological tests indicated that MAOAs, while showing an in hibitory activity on the haemorrhage induced by HLE, did not exhibit any ef fects due to the R and R-1 substituents. (C) 2000 Editions scientifiques et medicales Elsevier SAS.