Novel erythromycin derivatives with aryl groups tethered to the C-6 position are potent protein synthesis inhibitors and active against multidrug-resistant respiratory pathogens
| Autor: | Patty Ewing, Angela M. Nilius, Leping Li, Ping Zhong, Zhenkun Ma, Peter A. Nemoto, Richard F. Clark, Rupp Michael J, Zhensheng Cao, Daniel T. W. Chu, Michael J. Mitten, Jeff Alder, Robert K. Flamm, Ly Tam Phan, Hong Yong, George Griesgraber, Antony A Brazzale, Sanyi Wang, Jacob J. Plattner, Virginia D. Shortridge, Yat Sun Or, J. Meulbroek, Suoming Zhang, Xiaolin Zhang |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Ketolides Staphylococcus aureus Transcription Genetic Streptococcus pyogenes Erythromycin medicine.disease_cause Chemical synthesis Mice Structure-Activity Relationship In vivo Drug Discovery Protein biosynthesis medicine Animals Lung Respiratory Tract Infections Antibacterial agent Protein Synthesis Inhibitors Cell-Free System Chemistry Haemophilus influenzae In vitro Drug Resistance Multiple Anti-Bacterial Agents Rats Multiple drug resistance Streptococcus pneumoniae Biochemistry Protein Biosynthesis Molecular Medicine Carbamates Ribosomes medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 44(24) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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