Novel Erythromycin Derivatives with Aryl Groups Tethered to the C-6 Position Are Potent Protein Synthesis Inhibitors and Active against Multidrug-Resistant Respiratory Pathogens

作者：Zhenkun Ma, Richard F. Clark, Antony Brazzale, Sanyi Wang, Michael Rupp, Leping Li, George Griesgraber, Suoming Zhang, Hong Yong, Ly Phan, Peter Nemoto, Daniel T. W. Chu, Jacob J. Plattner, Xiaolin Zhang, Ping Zhong, Zhensheng Cao, Angela M. Nilius, Virginia D. Shortridge, Robert K. Flamm, Michael J. Mitten, Jon Meulbroek, Patty J. Ewing, Jeff Alder, Yat Sun Or · 发表于：Journal of Medicinal Chemistry · 年份：2001 · DOI：10.1021/jm0102349 · 被引用次数：112 · 研究领域：Pneumonia and Respiratory Infections、Pneumocystis jirovecii pneumonia detection and treatment、Carbohydrate Chemistry and Synthesis

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.