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Synthesis and Antibacterial Activity of a Novel Series of Acylides:  3-O-(3-Pyridyl)acetylerythromycin A Derivatives

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journal contribution
posted on 20.05.2003 by Tetsuya Tanikawa, Toshifumi Asaka, Masato Kashimura, Keiko Suzuki, Hiroyuki Sugiyama, Masakazu Sato, Kazuya Kameo, Shigeo Morimoto, Atsushi Nishida
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 (MLSB)-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.