A novel series of 3-ethoxyquinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT₃ 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 (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The 5-HT₃ receptor antagonism was evaluated in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT₃ agonist, 2-methy-5-HT, which was expressed in the form of pA₂ values. Compound 6h (3-ethoxyquinoxalin-2-yl)(4-methylpiperazin-1-yl)methanone was found to be the most active compound, which expressed a pA₂ value of 7.7. In forced swim test, the compounds with higher pA₂ value exhibited good anti-depressant-like activity and compounds with lower pA₂ value failed to show activity as compared to the vehicle-treated group.

根据5-HT ₃受体拮抗剂的药理学要求，使用基于配体的方法设计了一系列新的3-乙氧基喹喔啉-2-羧酰胺。在1-（3-二甲基氨基丙基）-3-乙基碳二亚胺盐酸盐（EDC·HCl）和1-羟基苯并三唑（HOBt）存在下，通过与适当的胺偶联，由关键中间体3-乙氧基喹喔啉-2-羧酸合成所需的羧酰胺）。在豚鼠回肠纵向肌肉肌层神经丛制备物中，针对5-HT ₃激动剂2-甲基-5-HT评估了5-HT ₃受体拮抗作用，该激动剂以p A ₂值的形式表达。化合物6h发现（3-乙氧基喹喔啉-2-基）（4-甲基哌嗪-1-基）甲酮是活性最高的化合物，其p A ₂值为7.7。在强制游泳试验中，与赋形剂处理组相比，具有较高p A ₂值的化合物表现出良好的抗抑郁样活性，而具有较低p A ₂值的化合物没有表现出活性。