Quinoxalin-2-carboxamides: synthesis and pharmacological evaluation as serotonin type-3 (5-HT₃) receptor antagonists

Abstract

A series of quinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT₃ receptor antagonists and synthesized by condensing the carboxylic group of quinoxalin-2-carboxylic acid with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole. The structures of the synthesized compounds were confirmed by physical and spectroscopic data. The carboxamides were evaluated for their 5-HT₃ receptor antagonisms in longitudinal muscle-myenteric plexus preparation from guinea pig ileum against 5-HT₃ agonist, 2-methy-5-HT. All the synthesized compounds showed 5-HT₃ receptor antagonism, (4-benzylpiperazin-1-yl)(quinoxalin-2-yl)methanone was the most potent compound among this series.

Keywords::

• Quinoxalin-2-carboxamides
• serotonin
• 5-HT₃ receptor antagonists
• quinoxaline

Acknowledgements

The authors thank the University Grants Commission (UGC), India, Birla Institute of Technology & Science (BITS), Pilani, India and SAIF, Panjab University, Chandigarh, India for providing financial support, laboratory and analytical facilities, respectively.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.