Some monocyclic beta-lactam derivatives of types II (1a-5a) and III (1b-5b), designed as analogs of type I derivatives, in which the C-4 aryloxy group of I is replaced by an oximate moiety, were synthesized and tested in vitro for their inhibitory activity towards porcine pancreatic (PPE) and human leukocyte (HLE) elastases. All compounds were found to be inactive on PPE. While 1b-5b did not display any appreciable activity towards HLE, compounds 1a-5a exhibited a marked inhibitory activity on this enzyme. The most active in vitro type-II compound 4a and the derivative 5a, whose molecular Structure presents a carboxylic moiety like type-I reference drug 14, were tested in vivo for their human sputum elastase inhibitory activity in elastase-induced lung hemorrhage in mice: they proved to possess an appreciable inhibitory activity even if somewhat lower than might have been expected on the basis of their activity indices obtained in the in vitro tests.

New beta-lactam monocyclic inhibitors of human elastases: synthesis and anti-elastase properties of 1-carbamoyl-4-methyleneaminoxyazetidinone derivatives

MACCHIA, MARCO;ORLANDINI, ELISABETTA;ROSSELLO, ARMANDO
1997

Abstract

Some monocyclic beta-lactam derivatives of types II (1a-5a) and III (1b-5b), designed as analogs of type I derivatives, in which the C-4 aryloxy group of I is replaced by an oximate moiety, were synthesized and tested in vitro for their inhibitory activity towards porcine pancreatic (PPE) and human leukocyte (HLE) elastases. All compounds were found to be inactive on PPE. While 1b-5b did not display any appreciable activity towards HLE, compounds 1a-5a exhibited a marked inhibitory activity on this enzyme. The most active in vitro type-II compound 4a and the derivative 5a, whose molecular Structure presents a carboxylic moiety like type-I reference drug 14, were tested in vivo for their human sputum elastase inhibitory activity in elastase-induced lung hemorrhage in mice: they proved to possess an appreciable inhibitory activity even if somewhat lower than might have been expected on the basis of their activity indices obtained in the in vitro tests.
Balsamo, A; Asti, C; BELFIORE M., S; Brandolini, L; Cercignani, G; Gentili, D.; Macchia, Marco; Mantovanini, M; Orlandini, Elisabetta; Rossello, Armando
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/202901
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