Novel Clarithromycin Analogs with C-4" 2-arylbenzimidazolyl Bishydrazide Side Chain: Synthesis and Antibacterial Evaluation

作者：Qi, Yunkun; Ma, Ruixin; Li, Xin; Hu, Yue; Ma, Siti; Cong, Chao; Ma, Xiaodong; Cui, Wenping; Ma, Shutao

来源：Letters in Drug Design and Discovery, 2011, 8(10): 966-971.

DOI：10.2174/157018011797655269

• Antibacterial activity
• Benzimidazolyl derivatives
• Carbamates
• Clarithromycin
• Resistance
• Synthesis

A series of novel 4 ''-O-2-arylbenzimidazolyl derivatives of clarithromycin were synthesized and evaluated. These 4 ''-O-2-arylbenzimidazolyl derivatives demonstrated excellent activity against erythromycin-susceptible strains and showed remarkably improved activity against erythromycin-resistant strains compared with the references. In particular, compound 7c, which possesses the terminal 2-(2-methoxyphenyl) benzimidazolyl group on the C-4 '' bishydrazide side chain, not only presented the most potent activity against erythromycin- susceptible Streptococcus pneumoniae ATCC49619 and Staphylococcus aureus ATCC25923, exhibiting 4-fold and 4-fold higher efficacy than the parent clarithromycin, but also displayed the highest activity against erythromycin- resistant Streptococcus pneumoniae expressing the mef gene and the erm gene, which was 133-fold and 32-fold better than clarithromycin or azithromycin, respectively.

• 出版日期2011-12
• 单位青岛大学; 山东大学