Synthesis and Inhibition of Human Leucocyte Elastase by Functionalized N-Aryl Azetidin-2-ones: Effect of Different Substituents on the Aromatic Ring

Abstract

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.