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

被引：26

作者：

Kapic, Samra ^{[1
]}

Paljetak, Hana Cipcic ^{[1
]}

Alihodzic, Sulejman ^{[1
]}

Antolovic, Roberto ^{[1
]}

Haber, Vesna Erakovic ^{[1
]}

Jarvest, Richard L. ^{[2
]}

Holmes, David J. ^{[3
]}

Broskey, John P. ^{[3
]}

Hunt, Eric ^{[4
]}

机构：

[1] GlaxoSmithKline Res Ctr Zagreb Ltd, HR-10000 Zagreb, Croatia

[2] GlaxoSmithKline Inc, Stevenage SG1 2NY, Herts, England

[3] GlaxoSmithKline Inc, Collegeville, PA 19426 USA

[4] GlaxoSmithKline Inc, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 17期

关键词：

Tethered macrolides; 6-(omega-Carboxy)-alkyl-N(1)-ethyl-3-carboxylquinolones; Antimicrobial activity; Structure-activity relationship; ANTIBACTERIAL ACTIVITY; STREPTOCOCCUS-PNEUMONIAE; KETOLIDE ANTIBIOTICS; DIFFERENT GENOTYPES; NMR-SPECTROSCOPY; ERYTHROMYCIN; DERIVATIVES; AZITHROMYCIN; PATHOGENS; TELITHROMYCIN;

D O I：

10.1016/j.bmc.2010.06.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 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. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6569 / 6577

页数：9

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