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Updated: Jun 10, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
6-Alkylquinolone-3-carboxylic acid tethered to macrolides synthesis and antimicrobial profile
Samra Kapić1, Hana Cipcić Paljetak, Sulejman Alihodzić
1GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. samra.y.kapic@gsk.com
Abstract:
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. Quinolone-linker intermediates were prepared by Sonogashira-type C(6)-alkynylation of 6-iodo-quinolone precursors. In the last step, 4'' site-selective acylation of 2'-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, 4''-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.
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