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A series of novel 3-O-arylalkylbenzamide derivatives as FtsZ inhibitors was designed, synthesized and evaluated for their cell division inhibitory activity against B. subtilis and S. aureus, and in vitro antibacterial activity against various phenotypes of Gram-positive bacteria. This series showed significantly improved on-target activity and in vitro antibacterial activity compared with 3-MBA. Among them, 3-O-alkylbenzamids 4–8 and 3-O-bromoalkylbenzamides 9 and 10 showed significantly improved activity against three phenotypes of S. aureus ATCC25923, S. aureusATCC29213 (MRSA) and S. aureus PR. Preliminary structure-activity relationships indicated that the extension of 3-O-alkyl side chain resulted in a substantial improvement in the antibacterial activity, and the small group like methyl or ethyl group at the position 1–3 of the 3-O-alkyl side chain did not affect the antibacterial activity while the large group such as benzene or heterocycle at the position 4 or 5 of the 3-O-alkyl side chain could lead to poor antibacterial activity.

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"-Obisamide chain with six atoms from the 4"-oxygen atom to the terminal 3,5-dinitrophenyl group.