运用分子模拟和计算机辅助药物设计专家系统Apex对镇痛药物结构和活性知识数据库中哌替啶类进行系统的构效关系研究 ,确立了该类药物的药效团 ,并依此设计、合成了两个结构新颖的哌替啶类镇痛药物 (Ⅰ )和 (Ⅱ ) .生物筛选结果表明 :化合物 (Ⅰ )和 (Ⅱ )具有显著的镇痛活性 ,其中化合物 (Ⅰ )的镇痛效价 (ED50 =7 7mg/kg ,s.c)高于哌替啶代表药物度冷丁 ,有希望成为新的先导化合物 . Using molecular modeling and computer aided drug design expert system Apex system structure-activity relationship study of pethidine in analgesic structure and activity knowledge database, established the pharmacophore of such drugs, and accordingly designed and synthesized Two novel pethidine analgesics (Ⅰ) and (Ⅱ) showed that the compounds (Ⅰ) and (Ⅱ) had significant analgesic activities, of which the analgesic potency of compound (Ⅰ) (ED50 = 7 7 mg / kg, sc) is higher than that of pethidine for the drug pethidine, promising to be the new lead compound.