帕瑞昔布钠有关物质的合成  

Synthesis of the Related Substances of Parecoxib Sodium

作　　者：张乃华 张文文 鲍广龙 郭新亮 张贵民 ZHANG Naihua;ZHANG Wenwen;BAO Guanglong;GUO Xinliang;ZHANG Guimin(Lunan Pharmaceutical Group Co.,Ltd.,Linyi 273400;International Pharmaceutical Engineering Lab.of Shandong Province,Linyi 273400)

机构地区：[1]鲁南制药集团股份有限公司,山东临沂273400 [2]山东省药物国际化工程实验室,山东临沂273400

出　　处：《中国医药工业杂志》2020年第10期1271-1276,共6页Chinese Journal of Pharmaceuticals

摘　　要：为控制环氧合酶-2抑制剂帕瑞昔布钠的质量,本研究合成了5个有关物质,分别为N-[[4-(3-甲基-5-苯基异噁唑-4-基)苯基]磺酰基]丙酰胺(有关物质A),4,4'-[磺酰基双(4,1-亚苯基)]双(5-甲基-3-苯基异噁唑)(有关物质B),3,3'-(5-甲基异噁唑-3,4-二基)二苯磺酰胺(有关物质C),N,N'-[(5-甲基异噁唑-3,4-二基)双(3,1-亚苯磺酰基)]二丙酰胺(有关物质D)和N-[[4-(5-甲基-4-苯基异噁唑-3-基)苯基]磺酰基]丙酰胺(有关物质E)。其中有关物质C和D未见文献报道,有关物质A的制备方法也未见报道,以上有关物质的结构均经MS、^1H NMR和^13C NMR确证,可作为帕瑞昔布钠质量研究的对照物。In order to control the quality of parecoxib sodium,a cyclooxygenase-2 inhibitor,five related substances,namely N-[[4-(3-methyl-5-phenylisoxazol-4-yl)phenyl]sulfonyl]propionamide(related substance A),4,4'-[sulfonylbis(4,1-phenylene)]bis(5-methyl-3-phenylisoxazole)(related substance B),3,3'-(5-methylisoxazol-3,4-diyl)dibenzenesulfonamide(related substance C),N,N'-[(5-methylisoxazol-3,4-diyl)bis(3,1-phenylenesulfonyl)]-dipropionamide(related substance D)and N-[[4-(5-methyl-4-phenylisoxazol-3-yl)phenyl]sulfonyl]propionamide(related substance E)were synthesized in this paper.Among them,neither related substances C and D nor the preparation method of related substance A has been found in literature.The structures of above related substances were confirmed by MS,1H NMR and 13C NMR,which could be used as the references for quality control of parecoxib sodium.

关 键 词：帕瑞昔布钠 环氧合酶-2(COX-2)抑制剂 有关物质 合成 

分 类 号：R914.5[医药卫生—药物化学]