维格列汀的空间构型与稳定性的关系  

Relationship between Configuration and Stability of Vildagliptin

作　　者：杨杰 朱峰 李党 YANG Jie;ZHU Feng;LI Dang(Hainan Haiyao Co.,Ltd.,Hainan Haikou 570311;China Meheco Sanyang Pharma Co.,Ltd.,Hainan Haikou 570312;Hainan Huluwa Pharmaceutical Group Co.,Ltd.,Hainan Haikou 570311,China)

机构地区：[1]海南海药股份有限公司,海南海口570311 [2]海南通用三洋药业有限公司,海南海口570312 [3]海南葫芦娃药业集团股份有限公司,海南海口570311

出　　处：《广州化工》2023年第13期95-98,共4页GuangZhou Chemical Industry

摘　　要：探讨维格列汀的空间结构及其稳定性的关联性。研究采用溶剂挥发法培养得到维格列汀的单晶,运用X射线单晶衍射技术对其立体结构进行解析。该化合物晶态下分子间存在氢键作用,相邻分子间凭借一对氢键形成类二聚体结构,以范德华力和氢键维系其在空间的稳定排列。质量标准中维格列汀的pH为9.7~10.7,因而在碱性和一定湿度下,在辅料微晶纤维素的作用下,破坏分子结构中的氢键,金刚烷上氨基碱性增强,易于进攻吡咯烷上氰基进而环合,这可能是长期放样或加入微晶纤维素,易产生杂质维格列汀环脒的原因。To study the spatial configuration of vildagliptin and its correlation with stability,a single crystal of vildagliptin was cultivated by solvent evaporation method,and the stereoscopic configuration was characterized by X-ray single crystal diffraction.The results showed that hydrogen bonds were presented in the crystalline state,two adjacent molecules formed quasi-dimer via a pair of hydrogen bonds between them,and the stable arrangement in space was maintained by van der waals forces and hydrogen bonds.The pH of vildagliptin in the quality standard was 9.7~10.7,therefore,the hydrogen bond in the molecular structure was destroyed under the action of alkalinity and humidity or excipient microcrystalline cellulose,the amino alkalinity on adamantane cycle was enhanced,and it was easy to attack the cyano group on pyrrolidine cycle and then cyclize,which explained the possible reason why it was esay to produce the vigliptin cyclic amidine by the long term setting out and adding micro-crystalline cellulose.

关 键 词：维格列汀 单晶培养 维格列汀环脒 氢键 

分 类 号：R914[医药卫生—药物化学]