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

Autori
Kapić, Samra ; Čipčić Paljetak, Hana ; Alihodžić, Sulejman ; Antolović, Roberto ; Eraković Haber, Vesna ; Jarvest, Richard L. ; Holmes, David J. ; Broskey, John P. ; Hunt, Eric

Izvornik
Bioorganic & medicinal chemistry (0968-0896) 18 (2010), 17; 6569-6577

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

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

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA