Design and synthesis of novel benzimidazole derivatives as anti-tuberculosis agents / 药学学报
Acta Pharmaceutica Sinica
; (12): 644-651, 2014.
Article
in En
| WPRIM
| ID: wpr-245033
Responsible library:
WPRO
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.
Full text:
1
Index:
WPRIM
Main subject:
Pharmacology
/
Structure-Activity Relationship
/
Tuberculosis
/
Benzimidazoles
/
Drug Design
/
Chemistry
/
Drug Therapy
/
Antitubercular Agents
Limits:
Humans
Language:
En
Journal:
Acta Pharmaceutica Sinica
Year:
2014
Type:
Article