title: Synthesis and inhibition of human leucocyte elastase by functionalized N-aryl azetidin-2-ones: effect of different substituents on the aromatic ring.
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 beta-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 beta-lactams proved to be good inactivators of human leucocyte elastase.
authors.affiliation: SIRCOB, Université de Versailles-St Quentin en Y., France.
authors.forename: R
authors.initials: R
authors.lastname: Joyeau
authors.forename: A
authors.initials: A
authors.lastname: Felk
authors.forename: S
authors.initials: S
authors.lastname: Guilaume
authors.forename: M
authors.initials: M
authors.lastname: Wakselman
authors.forename: I
authors.initials: I
authors.lastname: Vergely
authors.forename: C
authors.initials: C
authors.lastname: Doucet
authors.forename: N
authors.initials: N
authors.lastname: Boggetto
authors.forename: M
authors.initials: M
authors.lastname: Reboud-Ravaux
mesh_terms: D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D015842:Serine Proteinase Inhibitors / Q000096:biosynthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D015842:Serine Proteinase Inhibitors; D019272:Leukocyte Elastase