化工进展
化工進展
화공진전
CHEMICAL INDUSTRY AND ENGINEERING PROGRESS
2014年
6期
1521-1525,1532
,共6页
塞来昔布%合成%工艺优化
塞來昔佈%閤成%工藝優化
새래석포%합성%공예우화
Celecoxib%synthesis%process optimization
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。
塞來昔佈（西樂葆）作為首箇選擇性COX-2抑製劑類非甾體類抗炎藥，主要通過抑製環氧閤酶（COX）中的2型酶蛋白阻斷前列腺素生物閤成過程來實現抗炎作用，對胃腸道副作用較于傳統抗炎藥要小得多，其鎮痛抗炎活性具有很大的研究價值和廣闊的應用前景。西樂葆上市以來，一直是全毬暢銷藥物。近年來，國內對西樂葆的需求日益增長，其較好的開髮前景也備受關註。其化閤物專利2015年（補髮延期）到期。國內外對塞來昔佈的閤成報道較多，本文綜述瞭通過脫水環閤、環加成、偶聯、Michael加成、催化作用、芳基化等不同反應機理閤成塞來昔佈的方法。著重分析瞭傳統的酯縮閤和脫水環閤兩步過程製備塞來昔佈的工藝優化過程。得齣傳統的脫水環閤的方法反應緩和穩定，適閤工業化生產，其區域異構體雜質可以通過閤適的重結晶溶劑去除。製得的塞來昔佈可達國傢藥品標準。
새래석포（서악보）작위수개선택성COX-2억제제류비치체류항염약，주요통과억제배양합매（COX）중적2형매단백조단전렬선소생물합성과정래실현항염작용，대위장도부작용교우전통항염약요소득다，기진통항염활성구유흔대적연구개치화엄활적응용전경。서악보상시이래，일직시전구창소약물。근년래，국내대서악보적수구일익증장，기교호적개발전경야비수관주。기화합물전리2015년（보발연기）도기。국내외대새래석포적합성보도교다，본문종술료통과탈수배합、배가성、우련、Michael가성、최화작용、방기화등불동반응궤리합성새래석포적방법。착중분석료전통적지축합화탈수배합량보과정제비새래석포적공예우화과정。득출전통적탈수배합적방법반응완화은정，괄합공업화생산，기구역이구체잡질가이통과합괄적중결정용제거제。제득적새래석포가체국가약품표준。
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.
