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