title: Design, synthesis and evaluation of D,D-peptidase and beta-lactamase inhibitors: azapeptides, oxapeptides and related heterocycles.
abstract: 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.
authors.affiliation: Laboratoire de Chimie Organique de Synthèse, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Marchand-Brynaert
authors.forename: P
authors.initials: P
authors.lastname: Mougenot
authors.forename: Y
authors.initials: Y
authors.lastname: Combret
authors.forename: D
authors.initials: D
authors.lastname: Belotti
authors.forename: N
authors.initials: N
authors.lastname: Guillot
authors.forename: L
authors.initials: L
authors.lastname: Ghosez
mesh_terms: 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
chemical_list: D005656:Fungal Proteins; D006571:Heterocyclic Compounds; D007093:Imidazoles; D010080:Oxazoles; D065093:beta-Lactamase Inhibitors; C022325:aspartic proteinase A; D016282:Aspartic Acid Endopeptidases; D000409:Alanine