15745-94-5Relevant articles and documents
4-Oxo-β-lactams (azetidine-2,4-diones) are potent and selective inhibitors of human leukocyte elastase
Mulchande, Jalmira,Oliveira, Rudi,Carrasco, Marta,Gouveia, Luís,Guedes, Rita C.,Iley, Jim,Moreira, Rui
experimental part, p. 241 - 253 (2010/04/30)
Human leukocyte elastase (HLE) is a serine protease stored in and secreted from neutrophils that plays a determinant role in the pathogenesis of several lung diseases. 4-Oxo-β-lactams, previously reported as acylating agents of porcine pancreatic elastase, were found to be selective and potent inhibitors of HLE. Structure - activity relationship analysis showed that inhibitory activity is very sensitive to the nature of C-3 substituents, with small alkyl substituents such as a gem-diethyl group improving the inhibitory potency when compared to gem-methyl benzyl or ethyl benzyl counterparts. 4-Oxo-β-lactams containing a heteroarylthiomethyl group on the para position of an N 1-aryl moiety afforded highly potent and selective inhibition of HLE, even at a very low inhibitor to enzyme ratio, as shown by the kon value of 3.24 x 106 M-1 s-1 for 6f. The corresponding ortho isomers were 40- to 90-fold less potent.
