engleski

6-Alkylquinolone-3-carboxylic acid tethered to macrolides synthesis and antimicrobial profile

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.

tethered macrolides; 6-(x-carboxy)-alkyl-N(1)-ethyl-3- carboxylquinolones; aAntimicrobial activity; structure–activity relationship

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