Synthesis and antibacterial activity of novel 11-O- phenethylcarbamoylazithromycin derivatives with 4″-elongated side chains

Novel structural series of 11-O-phenethylcarbamoyl-4 "-O-((benzamido) alkyl) carbamoylazithromycin derivatives were synthesized and evaluated for their in vitro antibacterial activities. The 11,4 "-modified azithromycin derivatives displayed not only excellent activity against erythromycin- susceptible S. pneumonia resemble to the references, but also remarkably improved activity against three erythromycin- resistant S. pneumoniae expressing the erm gene, the mef gene, or the erm and mef genes, respectively, compared with the references. In particular, compound 6c was found to possess the most potent activity against both erythromycin- susceptible S. pneumoniae and S. aureus, and three erythromycin- resistant S. pneumoniae, which is characterized by both 11-O-phenethylcarbamoyl group and 4 "-O-bisamide chain with six atoms from the 4 "-oxygen atom to the terminal 3,5-dinitrophenyl group.