Discovery of new anti-depressants from structurally novel 5-HT3 receptor antagonists: Design, synthesis and pharmacological evaluation of 3-ethoxyquinoxalin-2-carboxamides

✍ Scribed by Radhakrishnan Mahesh; Thangaraj Devadoss; Dilip Kumar Pandey; Shvetank Bhatt

• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 281 KB
• Volume: 21
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.12.064

✦ Synopsis

A novel series of 3-ethoxyquinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT 3 receptor antagonist using ligand-based approach. The desired carboxamides were synthesized from the key intermediate, 3-ethoxyquinoxalin-2-carboxylic acid by coupling with appropriate amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCÁHCl) and 1-hydroxybenzotriazole (HOBt). The 5-HT 3 receptor antagonism was evaluated in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT 3 agonist, 2-methy-5-HT, which was expressed in the form of pA 2 values. Compound 6h (3-ethoxyquinoxalin-2-yl)(4-methylpiperazin-1yl)methanone was found to be the most active compound, which expressed a pA 2 value of 7.7. In forced swim test, the compounds with higher pA 2 value exhibited good anti-depressant-like activity and compounds with lower pA 2 value failed to show activity as compared to the vehicle-treated group.