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

A novel series of acylides, 3-<i>O-</i>(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<sub>B</sub>)-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as <i>H. influenzae</i>. 6,9:11,12-Dicarbonate acylide <b>47</b> (FMA0122) was twice as active against <i>H. influenzae</i> than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide <b>19</b> (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.