Synthesis and inhibitory activity towards human leukocyte elastase of new 7 alpha-methoxy and 7 alpha-chloro (2-acyloxymethyl) cephem derivatives

Some new cephem derivatives of types 4 and 5, viewed as analogues of type I esters in which the atomic sequence of the C-2 ester group is formally inv erted, were synthesised and tested in vitro for their inhibitory activity t owards human leukocyte elastase and porcine pancreatic elastase. An examina tion of the inhibition data obtained for the new type 4 and 5 derivatives, while exhibiting a considerable reduction in their activity against porcine pancreatic elastase, indicated that these compounds still maintain an appr eciable inhibitory activity against human leukocyte elastase. On this basis the new type of C-2 substitution appears to contribute to the research of new, potentially interesting, cephalosporinic human leukocyte elastase inhi bitors. (C) 2001 Editions scientifiques et medicales Elsevier SAS.