替诺福韦艾拉酚胺半D-（）-酒石酸盐的制备及其稳定性研究.PDFVIP

替诺福韦艾拉酚胺半 D-()-酒石酸盐的制备及其稳定性研究  陈鸿翔 1,2 ，毛建丰 2 ，盛荣 1*(1.浙江大学药学院，杭州 310058 ；2.杭州和泽医药科技有限公司，杭州 310018) 摘要：目的 制备替诺福韦艾拉酚胺半 D-()-酒石酸盐，并开展稳定性研究。方法 以替诺福韦(PMPA)为原料，经亚磷 酸三苯酯缩合、二氯亚砜氯代、L- 丙氨酸异丙酯缩合制得替诺福韦艾拉酚胺，再与 D-()-酒石酸成盐。结果 制得的替 诺福韦艾拉酚胺半 D-()-酒石酸盐，经 1H-NMR 、31P-NMR 、MS 确证结构，并与半富马酸盐进行稳定性比较。结论 替 诺福韦艾拉酚胺半 D-()-酒石酸盐比半富马酸盐具有更好的稳定性，值得进一步开发。 关键词：替诺福韦艾拉酚胺；替诺福韦；D-()-酒石酸；稳定性 中图分类号：R914.5 文献标志码：B 文章编号：1007-7693(2017)07-0978-04 DOI: 10.13748/ki.issn1007-7693.2017.07.010 引用本文：陈鸿翔, 毛建丰, 盛荣. 替诺福韦艾拉酚胺半 D-()- 酒石酸盐的制备及其稳定性研究[J]. 中国现代应用药学, 2017, 34(7): 978-981. Preparation and Stability Research of Tenofoviral Afenamide D-()-Tartaric Acid Salt (2 ∶1) CHEN Hongxiang1,2 2 1* , MAO Jianfeng , SHENG Rong (1.College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; 2.Hangzhou Heze Pharmaceutical Technology Co., Ltd., Hangzhou 310018, China) ABSTRACT: OBJECTIVE To prepare tenofoviralafenamide D-()-tartaric acid salt(2:1)and to study its stability. METHODS Tenofovir (PMPA) was utiliazed as the starting material, condensed with triphenylphosphite, chlorinated by thionyl chloride, and then condensed with L-alanine isopropyl to obtain tenofoviralafenamide. Tenofoviralafenamide was reacted with D-()-tartaric acid to form the salt. RESULTS The chemical structure of tenofoviralafenamide D-()-tartaric acid salt (2 ∶1) was confirmed by 1H-NMR, 31P-NMR, MS. The stability of the compound was also studied and compared with tenofoviralafenamide hemifumarate. CONCLUSION The results showed that D-()-tartaric acid salt has a better effect on stability than hemifumarate salt. It is worthy to be futher developed. KEY WORDS: tenofov