Novel erythromycin derivatives with aryl groups tethered to the C-6 position are potent protein synthesis inhibitors and active against multidrug-resistant respiratory pathogens

被引：116

作者：

Ma, ZK ^{[1
]}

Clark, RF ^{[1
]}

Brazzale, A ^{[1
]}

Wang, SY ^{[1
]}

Rupp, MJ ^{[1
]}

Li, LP ^{[1
]}

Griesgraber, G ^{[1
]}

Zhang, SM ^{[1
]}

Yong, H ^{[1
]}

Phan, LT ^{[1
]}

Nemoto, PA ^{[1
]}

Chu, DTW ^{[1
]}

Plattner, JJ ^{[1
]}

Zhang, XL ^{[1
]}

Zhong, P ^{[1
]}

Cao, ZS ^{[1
]}

Nilius, AM ^{[1
]}

Shortridge, VD ^{[1
]}

Flamm, R ^{[1
]}

Mitten, M ^{[1
]}

Meulbroek, J ^{[1
]}

Ewing, P ^{[1
]}

Alder, J ^{[1
]}

Or, YS ^{[1
]}

机构：

[1] Abbott Labs, Infect Dis Res, Abbott Pk, IL 60064 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 24期

关键词：

D O I：

10.1021/jm0102349

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of erythromycin derivatives has been discovered with potent activity against key respiratory pathogens, including those resistant to erythromycin. These compounds are characterized by having an aryl group tethered to the C-6 position of the erythronolide skeleton. Extensive structural modification of the C-6 moiety led to the discovery of several promising compounds with potent activity against both mef- and erm-mediated resistant Streptoccoccus pneumoniae. Preliminary mechanistic studies indicated that the new macrolides are potent protein synthesis inhibitors, which interact with methylated ribosomes isolated from resistant organisms. In experimental animal models, these compounds exhibited excellent in vivo efficacy and balanced pharmacokinetic profiles.

引用

页码：4137 / 4156

页数：20

共 61 条

[1] Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives):: A new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens [J].