Design, synthesis and stability of N-acyloxymethyl- and N-aminocarbonyloxymethyl-2-azetidinones as human leukocyte elastase inhibitors.
A series of N-acyloxymethyl- and N-aminocarbonyloxymethyl derivatives of 2-azetidinones, 3, with different substituent patterns at the beta-lactam C-3 and C-4 positions, were designed as potential mechanism-based inhibitors for human leukocyte elastase and found to exhibit inhibitory potency and selectivity for the enzyme.
Clemente
A
A
INETI, Dep. Biotecnologia, Estrada das Palmeiras, Lisboa, Portugal.
Domingos
A
A
Grancho
A P
AP
Iley
J
J
Moreira
R
R
Neres
J
J
Palma
N
N
Santana
A B
AB
Valente
E
E
D001384:Azetidines / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D012680:Sensitivity and Specificity
C116379:2-azetidinone; D001384:Azetidines; D004791:Enzyme Inhibitors; D019272:Leukocyte Elastase