Human leucocyte elastase

Adeyemi, E.O., Neumann, S., Chadwick, V.S., Hodgson, H.J.F. and Pepys, M.B. (1985). Circulating human leucocyte elastase in patients with inflammatory bowel disease. Gut 26, 1306-1311. 

Doucet, C. Vergely, I. Reboud-Ravaux, M. Guilhem, J. Kobaiter, R. Joyeau, R. Wakselman, M. Inhibition of human leucocyte elastase by functionalized V-aryl azeti-din-2-ones. Stereospecific synthesis and chiral recognition of disymmetrically C3-substi-tuted P-lactams. Tetrahedron Asymmetry 1997, 8, 739-751. 

Joyeau, R. Felk, A. Guillaume, S. Vergely, I. Doucet, C. Boggetto, N. Reboud-Ravaux, M. Synthesis and inhibition of human leucocyte elastase by functionalized V-aryl azetidin-2-ones effect of different substituents on the aromatic ring. J. Pharm. Pharmacol. 1996, 48, 1218-1230. 

Kerrigan, J. E. Oleksyszyn, J. Kam, C.-M. Selzler, J. Powers, J. C. Mechanism-based isocoumarin inhibitors of human leucocyte elastase. Effects of the 7-amino substituent and the 3-alkoxy group in 3-alkoxy-7-amino-4-chloroisocoumarins on inhibitory potency. j. Med. Chem. 1995, 38, 544-552. 

Azolides used as inhibitors for monoamine oxidase1171 or human leucocyte elastase,1181 as inductors of recessive lethal genes in Drosophila,1191 as histamine H2-receptor antagonists,1201 as anti-ulcer agents,1211 or as pharmacophores for anthelmintic, analgesic, and antimicrobial activity 1221... 

Pulmonary Emphysema, Osteoarthritis Human Leucocyte Elastase (HLE)... 

Silicon Diols, Effective Inhibitors of Human Leucocyte Elastase... 

Human leucocyte elastase (HE) is released in response to inflammatory stimuli and is responsible for degradation of connective tissues and is implicated in respiratory distress syndrome, rheumatoid arthritis, chronic bronchitis, and pulmonary emphysema. Many inhibitors of HE have been described [5], usually of the electrophilic carbonyl type, and often the key Val-Pro-Val motif has been exploited for potent inhibitory activity (3 - 5, Fig. 3). Recently, sivelestat (6, HE IC50 = 44 nM), a member of an enzyme-acylating series, has been approved in Japan for the treatment of acute lung injury [6]. 

In vitro Inhibitory Activity of Human Leucocyte Elastase Inhibitors... 

The results presented have demonstrated the ability of silicon diols to have serine protease inhibitory activity. The silicon diol 9 is a potent human leucocyte elastase inhibitor. The fact that the silicon diol moiety can be used across the aspartyl, metaJlo, and serine gene mily of proteases shows the power of such a simple privileged structure within the drug design process. 

A. Baici and P. Bradamante. Interaction between human leucocyte elastase and chondroitin sulfate. Chem. Biol. Interact. 51 1 (1984). 

Arcadi, A., Asti, C., Caselli, G Marinelli, F. and Ruggirei, V. (1999) Synthesis and in vitro and in vivo evaluation of the 2-(6 -methoxy-3, 4 -dihydro-l -naphthyl)-4H-3,l-benzoxazin-4-one as a new potent substrate inhibitor of human leucocyte elastase. Biorganic ei Medicinal Chemistry Letters, 9, 1291-1294. 

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