Synthesis and Inhibition of Human Leucocyte Elastase by Functionalized N-Aryl Azetidin-2-ones: Effect of Different Substituents on the Aromatic Ring
Open Access
- 1 December 1996
- journal article
- Published by Oxford University Press (OUP) in Journal of Pharmacy and Pharmacology
- Vol. 48 (12) , 1218-1230
- https://doi.org/10.1111/j.2042-7158.1996.tb03927.x
Abstract
N-aryl-3,3-difluoroazetidin-2-ones featured by a latent electrophilic methylene quinoniminium function have been synthesized and evaluated as inhibitors of human leucocyte elastase. To promote hydrophobic interactions with the enzyme, to increase the rates of β-lactam ring opening and of benzylic group departure, or to induce hydrosolubility, these compounds incorporate on their aromatic ring either an alkyl moiety, a methoxy substituent or a carboxylic group. Some of these β-lactams proved to be good inactivators of human leucocyte elastase.Keywords
This publication has 27 references indexed in Scilit:
- Inhibition of human leukocyte elastase by functionalized N-aryl azetidin-2-ones: substituent effects at C-3 and benzylic positionsEuropean Journal of Medicinal Chemistry, 1995
- 2,6-Disubstituted Aryl Carboxylic Acids, Leaving Groups "Par Excellence" for Benzisothiazolone Inhibitors of Human Leukocyte ElastaseJournal of Medicinal Chemistry, 1994
- Neutrophils and host defence: The fight against infectionPublished by Cambridge University Press (CUP) ,1994
- A cyclopeptidic suicide substrate preferentially inactivates urokinase-type plasminogen activatorBiochemical and Biophysical Research Communications, 1991
- FunctionalizedN-aryl azetidinones as novel mechanism-based inhibitors of neutrophil elastaseFEBS Letters, 1991
- A survey of Hammett substituent constants and resonance and field parametersChemical Reviews, 1991
- Inhibition of human leukocyte elastase. 2. Inhibition by substituted cephalosporin esters and amidesJournal of Medicinal Chemistry, 1990
- Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia.Journal of Clinical Investigation, 1983
- Esterification of Amino Acids and Dipeptides under Mild Conditions; Part II: via Sodium SaltsSynthesis, 1979
- Strain effects in acyl transfer reactions. Part I. The kinetics of hydrolysis of some N-aryl-lactamsJournal of the Chemical Society, Perkin Transactions 2, 1972