Synthesis and inhibitory activity towards human leukocyte elastase of new 7alpha-methoxy and 7alpha-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 inverted, were synthesised and tested in vitro for their inhibitory activity towards human leukocyte elastase and porcine pancreatic elastase. An examination 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 appreciable 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 inhibitors.
Balsamo
A
A
Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università degli Studi di Pisa,Via Bonanno, 6, 56100, Pisa, Italy.
Cercignani
G
G
Gentili
D
D
Lapucci
A
A
Macchia
M
M
Orlandini
E
E
Rapposelli
S
S
Rossello
A
A
D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology*; D007962:Leukocytes / Q000201:enzymology*; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013552:Swine
D002511:Cephalosporins; D004791:Enzyme Inhibitors; D007769:Lactams; D010196:Pancreatic Elastase