摘要
目的合成国家一类抗过敏新药富马酸卢帕替芬,并制备富马酸卢帕替芬的新晶型(晶型A),为该药的成药晶型选择提供科学依据。方法采用酸加成盐法合成富马酸卢帕替芬;分别采用粉末X-射线衍射法、差热扫描量热法、扫描电子显微镜法等物理方法,对富马酸卢帕替芬晶型A样品进行表征。结果经工艺优化合成了富马酸卢帕替芬,其结构经1H-NMR、ESI-MS谱确证;并获得富马酸卢帕替芬晶型A,数据分析表明晶型A为棒状结晶;以衍射角(2θ±0.2)°位于13.6°(23%)、21.3°(30%)、29.1°(41%)为晶型A的特征峰;其熔点为(154±2)℃,在(180±2)℃左右发生分解。结论通过研究明确了富马酸卢帕替芬的合成工艺,成功确证了富马酸卢帕替芬晶型A的结构,对富马酸卢帕替芬成药开发提供良好的科学依据,对于其他新药开发具有参考意义。
In this study,a new national anti-allergic drug,rupatifen fumarate,was developed and a new crystalline form of rupatifen fumarate(crystal A)was prepared.The target compound was synthesized by acid addition salt method,and the crystal type A was characterized by powder X-ray diffraction,differential scanning calorimetry(DSC),scanning electron microscope and other physical methods.The characterization results showed that the crystal type A was a rod-shaped crystal,the characteristic peak of crystal A was(2θ±0.2)°at 13.6°(23%),21.2°(30%),29.1°(40%).Its melting point was(154±2)℃and decomposition occurs at about(180±2)℃.Through the study,the compound and crystal A of rupatifen fumarate were of great reference significance for the development of proprietary drugs of rupatifen fumarate.
作者
李琳
张亚珊
林伟
杨敏
林鹏飞
王海燕
LI Lin;ZHANG Ya-shan;LIN Wei;YANG Min;LIN Peng-fei;WANG Hai-yan(Fujian Mindong Rejuvenation Pharmaceutical Co.,Ltd.,Ningde 355300,China)
出处
《中国药物化学杂志》
CAS
CSCD
北大核心
2020年第7期405-409,共5页
Chinese Journal of Medicinal Chemistry
基金
国家“重大新药创制”科技重大专项(2018ZX09J18108-005)
福建省科技重大专项专题项目(2015YZ0002-2)
福建省区域发展项目(2017Y3010)
关键词
抗过敏
富马酸卢帕替芬
合成
晶型表征
antiallergy
rupatifen fumarate
synthesis
crystal structure characterization
