替格瑞洛的波谱特征与结构确证
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摘要
目的确证替格瑞洛的化学结构。方法通过紫外光谱(UV)、红外光谱(IR)、超高分辨傅里叶变换离子回旋质谱(FT-MS)、1D/2D核磁共振谱(NMR)、差热扫描量热分析(DSC)、热重/差热扫描量热同步综合热分析(TG/DSC)和X-射线粉末衍射(XRD)对替格瑞洛进行结构分析。结果通过解析证实了替格瑞洛的化学结构为(1S,2S,3R,5S)-3-[7-[[(1R,2S)-2-(3,4-二氟苯基)环丙基]氨基]-5-丙硫基三唑并[4,5-d]嘧啶-3-基]-5-(2-羟乙氧基)-1,2-环戊二醇。结论该方法准确可行,可为替格瑞洛的结构确证提供依据。
Objective To determine the chemical structure of ticagrelor. Methods Ultraviolet absorption spectrum(UV), infrared absorption spectroscopy(IR), Ultra-high resolution fourier-transform ion cyclotron resonance mass spectrometry(FT-MS), 1 D/2 D Nuclear magnetic resonance spectroscopy(NMR), Differential scanning calorimetry(DSC), Thermogravimetric/Differential scanning calorimetry synchronized comprehensive thermal Analysis(TG/DSC) and X-ray powder diffraction(XRD) were used to analyze the chemical structure of ticagrelor. Results The chemical structure of ticagrelor was(1 S, 2 S, 3 R, 5 S)-3-[7-[[(1 R, 2 S)-2-(3,4-difluorophenyl) cyclopropyl] amino]-5-propylsulfanyltriazolo[4, 5-d] pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1, 2-diol. Conclusion The method is accurate and practical, which can provide comprehensive reference for the structural identification of ticagrelor.
Objective To determine the chemical structure of ticagrelor. Methods Ultraviolet absorption spectrum(UV), infrared absorption spectroscopy(IR), Ultra-high resolution fourier-transform ion cyclotron resonance mass spectrometry(FT-MS), 1 D/2 D Nuclear magnetic resonance spectroscopy(NMR), Differential scanning calorimetry(DSC), Thermogravimetric/Differential scanning calorimetry synchronized comprehensive thermal Analysis(TG/DSC) and X-ray powder diffraction(XRD) were used to analyze the chemical structure of ticagrelor. Results The chemical structure of ticagrelor was(1 S, 2 S, 3 R, 5 S)-3-[7-[[(1 R, 2 S)-2-(3,4-difluorophenyl) cyclopropyl] amino]-5-propylsulfanyltriazolo[4, 5-d] pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1, 2-diol. Conclusion The method is accurate and practical, which can provide comprehensive reference for the structural identification of ticagrelor.
引文
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[2]Dobesh PP,Patel M. The PARTHENON clinical development program:the role of ticagrelor in patients with atherothrombotic disease[J]. Cardiovasc Drugs Ther,2017,31(4):1-12.
[3]熊琳,黄麟杰,李聪,等.临床药师运用循证药学处理抗血小板药物不良反应的药学服务[J].中南药学,2016,16(11):1641-1645.
[4]周晶,张海杰,浅论抗血小板药替格瑞洛遗传药理学和药效学特征的研究进展[J].当代医药论丛,2017,15(7):108-109.
[5]曹爱霖,钱皎,王卓,等.替格瑞洛致呼吸困难不良反应2例及其机制探讨[J].中南药学,2016,14(4):445-448.
[6]Teng RL,Butle K. Pharmacokinetic interaction study of ticagrelor and digoxin in healthy volunteers[J]. Eur J Clin Pharmacol,2014,34(8):529-536.
[7]李慕鹏,熊艳,陈小平.抗血小板药物替格瑞洛药代药效动力学及遗传药理学研究进展[J].中国临床药理学与治疗学,2014,19(2):214-222.
[8]李宁,马满玲.低剂量替格瑞洛应用于亚洲人群的临床研究进展[J].中南药学,2017,15(9):1262-1265.
[9]宋柳全,黎晓亮,何国欢.替格瑞洛临床应用概述[J].中国药师,2018,21(7):1269-1274.
[10]刘娟,邹耀松,陈荣霞,等.替格瑞洛在冠心病患者中的临床应用[J].中华保健医学杂志,2018,20(5):444-445.
[11]张银.替卡格雷合成研究进展[J].浙江化工,2015,46(1):8-15.
[12]阎欢,吴楠,吴进,等.替格瑞洛的合成[J].沈阳化工大学学报,2018,32(2):157-160.
[13]黄阳,王兵,刘颖,等.替卡格雷的合成工艺改进[J].合成化学,2015,23(7):650-652.
[14]李小东,廖祥伟,蒲道俊,等.替格瑞洛合成工艺的改进[J].合成化学,2016,24(11):994-997.
[15]霍丽茹,许麒麟,赵钦,等.替格瑞洛的晶体结构研究[J].中国现代应用药学,2017,34(6):868-870.
[16]霍美娣,雷勇胜,蒋庆峰,等.右佐匹克隆的波谱分析及结构确证[J].中南药学,2017,15(1):39-44.
[17]林辉,王正泽,赵磊,等.甲磺酸卡莫司他的波谱学数据与结构确证[J].中南药学,2016,14(12):1312-1315.
[18]谭蕾红,李静,王绪礼,等.新型降胆固醇药物依折麦布的波谱学解析与结构确证[J].中南药学,2015,13(6):606-609.
[19]胥维昌,母继荣. NMR在含氟芳香化合物结构鉴定中的应用[J].农药,2001,40(4):20-21.
[20]李临生,李燕,兰云军,等. 19F NMR的特点[J].波谱学杂志,2007,24(3):353-364.
[21]宁永成.有机化合物结构鉴定与有机波谱学[M].北京:科学出版社,2005.