6-Alkylquinolone-3-carboxylic acid tethered to macrolides synthesis and antimicrobial profile
| Autor: | John Broskey, Sulejman Alihodžić, David J. Holmes, Samra Kapić, Vesna Eraković Haber, Eric Hunt, Roberto Antolović, Hana Čipčić Paljetak, Richard L. Jarvest |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Stereochemistry
Carboxylic acid Clinical Biochemistry Pharmaceutical Science Ether Microbial Sensitivity Tests Azithromycin Quinolones tethered macrolides 6-(x-carboxy)-alkyl-N(1)-ethyl-3- carboxylquinolones aAntimicrobial activity structure–activity relationship Biochemistry Chemical synthesis Acylation Structure-Activity Relationship chemistry.chemical_compound Clarithromycin Drug Discovery Humans Molecular Biology Antibacterial agent chemistry.chemical_classification Bicyclic molecule Organic Chemistry Antimicrobial Anti-Bacterial Agents chemistry Molecular Medicine Macrolides Linker |
| Zdroj: | Bioorganic & Medicinal Chemistry. 18:6569-6577 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2010.06.048 |
| Popis: | Two series of clarithromycin and azithromycin derivatives with terminal 6-alkylquinolone-3-carboxylic unit with central ether bond in the linker were prepared and tested for antimicrobial activity. Quinolonelinker intermediates were prepared by Sonogashira-type C(6)-alkynylation of 6-iodo-quinolone precursors. In the last step, 400 site-selective acylation of 20-protected macrolides was completed with the EDC reagent, which selectively activated a terminal, aliphatic carboxylic group in dicarboxylic intermediates. Antimicrobial activity of the new series of macrolones is discussed. The most potent compound, 400-O-{; ; 6-[3-(3-carboxy-1-ethyl-4-oxo-1, 4-dihydroquinolin-6-yl)-propoxy]-hexanoyl}; ; -azithromycin (10), is highly active against bacterial respiratory pathogens resistant to macrolide antibiotics and represents a promising lead for further investigation. |
| Databáze: | OpenAIRE |
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