Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetylerythromycin A derivatives.

Abstract

A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.

• Authors: Tetsuya Tanikawa, Toshifumi Asaka, Masato Kashimura, Keiko Suzuki, Hiroyuki Sugiyama, Masakazu Sato, Kazuya Kameo, Shigeo Morimoto, Atsushi Nishida
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 46 Issue 13 Pg. 2706-15 (Jun 19 2003) ISSN: 0022-2623 [Print] United States
• PMID: 12801234 (Publication Type: Journal Article)

Chemical References

• 5-O-desosaminyl-3-O-(3-pyridyl)acetyl-6-O-methylerythronolide A 11,12-cyclic carbamate
• 5-O-desosaminyl-9-dihydro-3O-(3-pyridyl)acetylerythronolide A 6,9-11,12-dicyclic carbonate
• Anti-Bacterial Agents
• Macrolides
• Erythromycin

Topics

• Administration, Oral
• Animals
• Anti-Bacterial Agents (chemical synthesis, chemistry, pharmacology)
• Area Under Curve
• Drug Resistance, Multiple, Bacterial
• Erythromycin (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Haemophilus influenzae (drug effects)
• Macrolides (chemical synthesis, chemistry, pharmacology)
• Mice
• Staphylococcal Infections (mortality, prevention & control)
• Staphylococcus aureus (drug effects)
• Stereoisomerism
• Streptococcal Infections (mortality, prevention & control)
• Streptococcus pneumoniae (drug effects)
• Structure-Activity Relationship