替诺福韦艾拉酚胺半D-(-)-酒石酸盐的制备及其稳定性研究

    Preparation and Stability Research of Tenofoviral Afenamide D-(-)-Tartaric Acid Salt (2:1)

    • 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。

       

      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.

       

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