镇痛药物先导结构的设计、合成与筛选  

The Design,Synthesis and Screening of the Analgesic Lead Compounds

作　　者：郑志兵[1] 王丹心[1] 谢云德[1] 胡远东[1] 崔光耀[1] 阎远[1] 焦克芳[1] 李松[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药物化学杂志》2000年第1期43-45,共3页Chinese Journal of Medicinal Chemistry

基　　金：国家杰出青年科学基金!No .39825127;国家863计划生物技术领域基金;国家重点基础研究规划"重要疾病创新药物先导结构的发现和优化"

摘　　要：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 .The structure activity relationships of pethidine type drugs in the database were studied by using the softwares of molecular simulation and the Apex 3D Expert System of Compouter aided Drug Design.The main biophores of this kind of drugs were found.According to them,two pethidine type of analgesic drugs(Ⅰ) and (Ⅱ) with novel structures were designed and synthesized.The results of biological screening showed that compounds(Ⅰ) and (Ⅱ)had analgesic activity.The analgesic value of compound(Ⅰ)(ED 50 =7 7 mg/kg,( s.c ) was slightly higher than that of Dolantin which is the representative drug of Pethidine type analgesic drugs.The compound(Ⅰ)will become a leading compound for designing new analgesic drugs.

关 键 词：药物设计 镇痛药 药效基团 构效关系 合成 

分 类 号：R914.2[医药卫生—药物化学]