Synthesis and structure-activity relationships of new cephalosporins with aminoimidazoles at C-7. Effect of the pKa of the C-7 aminoimidazole on antibacterial spectrum and .BETA.-lactamase stability
| Autor: | G. M. Davies, A. Olivier, F. Jung, J. F. Kingston, J. D. Pittam, D. Boucherot, M. Joseph, C. Delvare, R. Brown, M. J. Betts, R. Stevenson |
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| Rok vydání: | 1993 |
| Předmět: |
Pharmacology
medicine.drug_class Chemistry Stereochemistry medicine.medical_treatment Cephalosporin Imidazoles Biological activity Microbial Sensitivity Tests beta-Lactamases Cephalosporins Mice Structure-Activity Relationship Broad spectrum Enzyme Stability Drug Discovery medicine Beta-lactamase Animals Structure–activity relationship Antibacterial activity Antibacterial agent |
| Zdroj: | The Journal of Antibiotics. 46:992-1012 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.7164/antibiotics.46.992 |
| Popis: | Cephalosporins with new aminoimidazole heterocycles at C-7 have been synthesized by reaction of anti-alpha-aminooximes with C-7 dihaloisocyanocephalosporins esters or by direct condensation of 2-fluoroimidazoles with C-7 aminocephalosporins esters. These compounds combine a broad spectrum of antibacterial activity, including Gram-negative and Gram-positive organisms with a good beta-lactamase stability. Activity is discussed in terms of its relationship to the pKa of the C-7 aminoimidazole heterocycle, basic C-7 aminoimidazole residues gave cephalosporins with the best beta-lactamase stability but the poorest activity against Gram-positive organisms. An additional interesting property of the C-7 imidazolylaminocephalosporins is the oral activity present in some compounds of this series. |
| Databáze: | OpenAIRE |
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