Synthesis and antibacterial activity of novel C12 ethyl ketolides

被引：19

作者：

Burger, Matthew T. ^{[1
]}

Hiebert, Christy ^{[1
]}

Seid, Mehran ^{[1
]}

Chu, Daniel T. ^{[1
]}

Barker, Lynn ^{[1
]}

Langhorne, Mike ^{[1
]}

Shawar, Ribhi ^{[1
]}

Kidney, Jolene ^{[1
]}

Desai, Manoj C. ^{[1
]}

Plattner, Jacob J. ^{[1
]}

机构：

[1] Chiron Corp, Biopharma Res, Oakland, CA 94608 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 16期

关键词：

ketolide; macrolide; ketolide antibiotic; macrolide antibiotic; antiinfective; antibiotic; ERYTHROMYCIN-A ANALOGS; MACROLIDE ANTIBIOTICS; BACTERIAL-RIBOSOMES; HIGHLY POTENT; CONFORMATIONAL-ANALYSIS; ANHYDROLIDE MACROLIDES; AQUEOUS-SOLUTION; HMR; 3647; AZITHROMYCIN; DERIVATIVES;

D O I：

10.1016/j.bmc.2006.04.032

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：

A novel series of C-12 ethyl erythromycin derivatives have been discovered which exhibit in vitro and in vivo potency against key respiratory pathogens, including those resistant to erythromycin. The C-12 modification involves replacing the natural C-12 methyl group in the erythromycin core with an ethyl group via chemical synthesis. From the C-12 ethyl macrolide core, a series of C-12 ethyl ketolides were prepared and tested for antibacterial activity against a panel of relevant clinical isolates. Several compounds were found to be potent against macrolide-sensitive and -resistant bacteria, whether resistance was due to ribosome methylation (erm) or efflux (mef). In particular, the C-12 ethyl ketolides U,4,4q,4m, and 4t showed a similar antimicrobial spectrum and comparable activity to the commercial ketolide telithromycin. The in vivo efficacy of several C-12 ethyl ketolides was demonstrated in a mouse infection model with Streptococcus pneumoniae as pathogen. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5592 / 5604

页数：13

共 38 条

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