The synthesis and evaluation of benzofuranones as β-Lactamase substrates
| Autor: | R. F. Pratt, D. Cabaret, M. Wakselman, S. A. Adediran, B Drouillat |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.drug_class
Stereochemistry Clinical Biochemistry Pharmaceutical Science Carboxamide Biochemistry Chemical synthesis beta-Lactamases Substrate Specificity Lactones chemistry.chemical_compound Drug Discovery medicine Reactivity (chemistry) Carboxylate Molecular Biology Benzofurans chemistry.chemical_classification Aqueous solution Bicyclic molecule Hydrolysis Organic Chemistry Biological activity Hydrogen-Ion Concentration Kinetics chemistry Molecular Medicine Lactone |
| Zdroj: | Bioorganic & Medicinal Chemistry. 9:1175-1183 |
| ISSN: | 0968-0896 |
| Popis: | 6- and 7-Carboxy-3-phenylacetamido-3H-1-benzofuran-2-one have been synthesized as potential beta-lactamase substrates and/or inhibitors. These compounds were prepared by lactonization of the corresponding, appropriately substituted phenylglycines. The latter compounds were prepared by either the Strecker or the Bücherer-Berg method. The benzofuran-2-ones were less stable in aqueous solution than the analogous acyclic phenaceturate esters but comparably stable to analogous benzopyran-2-ones. They differed from the latter compounds however in that the C-3 hydrogen of the furan-2-ones, adjacent to the lactone carbonyl group, was distinctly acidic; 7-carboxy-3-phenylacetamido-3H-1-benzofuran-2-one exists largely as an enolate at pH 7.5. The furan-2-ones were beta-lactamase substrates with reactivity very similar to the analogous acyclic phenaceturates. They were not, however, DD-peptidase inhibitors and are thus unlikely to have antibiotic activity. The structural basis for these observations is discussed. |
| Databáze: | OpenAIRE |
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