Citation

Gérard S, Nollet G, Vande Put J, Marchand-Brynaert J. Bioorg. Med. Chem. 2002; 10(12): 3955-3964.

Copyright

(Copyright © 2002, Elsevier Publishing)

DOI

10.1016/s0968-0896(02)00304-8

PMID

12413847

Abstract

A series of 1-alkoxycarbonyl-3-halogenoazetidin-2-ones, designed as potential suicide inhibitors of serine proteases, has been synthesized and evaluated against porcine pancreatic elastase (PPE). All the compounds were transient inhibitors, their activity depending mainly on the nature of the halogen substituent: bromo- and iodo- derivatives are more active (K(i) approximately 2-22 microM) than 3-chloroazetidinones (K(i) approximately 20-150 microM). The lipophilicity of the N-1 substituent appeared to exert a slightly positive effect.

Language: en

Keywords

Animals; Azetidines; Hydrophobic and Hydrophilic Interactions; Kinetics; Pancreatic Elastase; Serine Proteinase Inhibitors; Structure-Activity Relationship; Swine