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