Design and synthesis of novel benzimidazole derivatives as anti-tuberculosis agents.

Abstract

In recent studies some urea derivatives have been identified as potent anti-tuberculosis agents by targeting mycobacterial membrane protein large 3 (MmpL3). However, this compound series as exemplified by AU1235 exhibited poor in vitro pharmacokinetic profile. With AU1235 as the lead, we have identified a novel benzimidazole series as potential anti-tuberculosis agents by using scaffold hopping approach. Among these synthesized compounds, 2-aminobenzimidazole derivative 8b showed the potent anti-tuberculosis activity with the MIC value of 0.03 microg x mL(-1). This compound also showed improved metabolic stability compared to AU1235. Our investigation indicated that benzimidazole derivatives are the promising lead for further optimization as anti-tuberculosis agents.

• Authors: Hui-Ying Zhang, Bin Wang, Li Sheng, Dan Li, Dong-Feng Zhang, Zi-Yun Lin, Yu Lu, Yan Li, Hai-Hong Huang
• Journal: Yao xue xue bao = Acta pharmaceutica Sinica (Yao Xue Xue Bao) Vol. 49 Issue 5 Pg. 644-51 (May 2014) ISSN: 0513-4870 [Print] China
• PMID: 25151735 (Publication Type: Journal Article)

Chemical References

• Antitubercular Agents
• Benzimidazoles
• benzimidazole
• 2-aminobenzimidazole

Topics

• Antitubercular Agents (pharmacology)
• Benzimidazoles (chemistry, pharmacology)
• Drug Design
• Humans
• Structure-Activity Relationship
• Tuberculosis (drug therapy)