Beauve, C
Bouchet, Michèle
[UCL]
Touillaux, Roland
Fastrez, Jacques
[UCL]
Marchand-Brynaert, Jacqueline
[UCL]
A series of monocyclic azetidinones were prepared, bearing, at position C-3, an acetylamino or a bromo substituent, at position N-1, a carboxymethyl group protected as p-nitrobenzyl ester (PNB) and alpha-functionalized with a potential leaving group (LG). These structures were designed as potential suicide-inhibitors of enzymes containing a serine nucleophile in their active site. The beta-lactam ring of these molecules was found to be stable in phosphate buffer (pH 7.5), but the PNB ester was rapidly cleaved. This constitutes a practical method of in situ deprotection. Depending on the nature of the LG group on the carboxymethyl chain, substitution of this group (LG = F) or decarboxylation (LG = SO2Ph) was observed under hydrolytic conditions. The 1,3-disubstituted azetidinones were inactive against beta-lactamases of classes A, B, C, and D. Three compounds behaved as weak reversible inhibitors of porcine pancreatic elastase (PPE). (C) 1999 Elsevier Science Ltd. All rights reserved.
Bibliographic reference |
Beauve, C ; Bouchet, Michèle ; Touillaux, Roland ; Fastrez, Jacques ; Marchand-Brynaert, Jacqueline. Synthesis, reactivity and biochemical evaluation of 1,3-substituted azetidin-2-ones as enzyme inhibitors. In: Tetrahedron, Vol. 55, no. 46, p. 13301-13320 (1999) |
Permanent URL |
http://hdl.handle.net/2078.1/44093 |