Novel C-4″ modified azithromycin analogs with remarkably enhanced activity against erythromycin-resistant Streptococcus pneumoniae: The synthesis and antimicrobial evaluation

Three novel structural series of C-4″ modified azithromycin analogs with two amide groups, which were connected by different alkyl linkage, were designed, prepared and evaluated for their in vitro antibacterial activity against seven phenotypes of respiratory pathogens. Among them, 7d, 8j and 9j, as representatives of corresponding series, exhibited remarkably improved activity against erythromycin-resistant Streptococcus pneumoniae expressing the erm gene, the mef gene, and the erm and mef genes. In addition, 7a–c, 7f–h, 7j, 8d, 8g, 8i, 9a–b and 9i displayed favorable efficacy against erythromycin-resistant S. pneumoniaeA22072 expressing the mef gene.

Novel structural series of C-4″ bisamide azithromycin analogs were designed, prepared and evaluated in vitro. Compound 9j, as the representative derivative, exhibited remarkably improved antibacterial activity against erythromycin-resistant Streptococcus pneumoniae than the references.Figure optionsDownload as PowerPoint slideHighlights
► Three series of C-4″ bisamide azithromycin analogs were synthesized and evaluated.
► They have two amide groups connected by different linkage in the C-4″ side chain.
► Some of them showed greatly improved activity against erythromycin-resistant strains.
► Their resistance is encoded by the erm gene, the mef gene, and the erm and mef genes.