COX-2特异性抑制剂塞来昔布的合成研究进展  

Synthesis research progress in COX-2 inhibitors Celecoxib

作　　者：卢定强[1,2] 沈东[2] 凌岫泉[1] 

机构地区：[1]江苏省药物研究所,江苏南京211000 [2]南京工业大学药学院,江苏南京211000

出　　处：《化工进展》2014年第6期1521-1525,1532,共6页Chemical Industry and Engineering Progress

基　　金：江苏省博士后基金(51228004);中国博士后基金(51228006)项目

摘　　要：塞来昔布(西乐葆)作为首个选择性COX-2抑制剂类非甾体类抗炎药,主要通过抑制环氧合酶(COX)中的2型酶蛋白阻断前列腺素生物合成过程来实现抗炎作用,对胃肠道副作用较于传统抗炎药要小得多,其镇痛抗炎活性具有很大的研究价值和广阔的应用前景。西乐葆上市以来,一直是全球畅销药物。近年来,国内对西乐葆的需求日益增长,其较好的开发前景也备受关注。其化合物专利2015年(补发延期)到期。国内外对塞来昔布的合成报道较多,本文综述了通过脱水环合、环加成、偶联、Michael加成、催化作用、芳基化等不同反应机理合成塞来昔布的方法。着重分析了传统的酯缩合和脱水环合两步过程制备塞来昔布的工艺优化过程。得出传统的脱水环合的方法反应缓和稳定,适合工业化生产,其区域异构体杂质可以通过合适的重结晶溶剂去除。制得的塞来昔布可达国家药品标准。Celecoxib is the first selective COX-2 inhibitor of non-steroidal anti-inflammatory drugs, it mainly inhibit COX-2 enzyme protein which is necessary for prostaglandin biosynthesis process to achieve anti-inflammatory effects. Its side effects are much smaller than that of traditional anti-inflammatory drugs. Its analgesic anti-inflammatory activity is of great research value and broad application prospects. Since going public,Celebrex has been one of the world’s best selling drugs. In recent years,a growing domestic demand for celebrex and more attention has been paid to its good development prospect. The compound patent delay （reissue） expires in 2015. There are many reports on the synthesis of celecoxib at home and abroad. It is aimed at the synthesis progress of celecoxib by different reaction mechanism,such as dehydration,cyclization,cycloaddition,coupling,Michael addition,catalysis and arylation. We analyzed the traditional two-step preparation process of celecoxib by ester condensation and dehydration cyclization and its optimization process. It is concluded that the traditional method by dehydration cyclization is moderate and stable. It’s also suitable for industrialized production. The regional isomer impurity during the reaction can be removed by suitable recrystallization solvent. What’s more,the celecoxib we prepared can reach the national drug standards.

关 键 词：塞来昔布 合成 工艺优化 

分 类 号：O6-1[理学—化学]