Design, synthesis and evaluation of D,D-peptidase and beta-lactamase inhibitors: azapeptides, oxapeptides and related heterocycles.
Reactive molecules susceptible to form stable acyl enzyme intermediates with D,D-peptidases and beta-lactamases were designed as potential irreversible inhibitors of Penicillin Sensitive Enzymes (PSEs). The structures examined were a series of azapeptides and oxapeptides, both analogs of the D-Ala-D-Ala substrate, and some heterocycles, such as imidazolidinones and oxazolidinones, both analogs of the beta-lactam antibiotics. The various strategies investigated for their synthesis are described and discussed. Some biological results are reported.
Marchand-Brynaert
J
J
Laboratoire de Chimie Organique de Synthèse, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Mougenot
P
P
Combret
Y
Y
Belotti
D
D
Guillot
N
N
Ghosez
L
L
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D005656:Fungal Proteins / Q000037:antagonists & inhibitors*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors
D005656:Fungal Proteins; D006571:Heterocyclic Compounds; D007093:Imidazoles; D010080:Oxazoles; D065093:beta-Lactamase Inhibitors; C022325:aspartic proteinase A; D016282:Aspartic Acid Endopeptidases; D000409:Alanine