前体药物2',3',5'-三乙酰基-6-氮杂尿苷的水解
Hydrolysis of the prodrug, 2',3',5'-triacetyl-6-azauridine.
作者信息
Riley C M, Mummert M A, Zhou J, Schowen R L, Vander Velde D G, Morton M D, Slavik M
机构信息
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045-2504, USA.
出版信息
Pharm Res. 1995 Sep;12(9):1361-70. doi: 10.1023/a:1016238110533.
PURPOSE
The purposes were to study the kinetics of hydrolysis of 2',3',5'-triacetyl-6-azauridine (1) in aqueous solution (mu = 0.5) and to identify the main intermediates and products of the reaction.
METHODS
A stability indicating isocratic LC assay was used to study the rate of degradation of 1. A gradient LC assay was used to study the time courses of the degradants. The products of hydrolysis were isolated by preparative liquid chromatography and identified by 1H-NMR and CI-MS. The pKa value was obtained by potentiometric titration.
RESULTS
At 36.8 degrees C, the pH-rate profile of 1 in water was adequately described by a four-term rate equation. The intermediates were identified as the primary and secondary di-acetates, and the primary and secondary mono-acetates. The final product was 6-azauridine.
CONCLUSIONS
A simplified kinetic scheme could be used to describe the concentration-time profiles of 1, the intermediates and the final product.
目的
研究2',3',5'-三乙酰基-6-氮杂尿苷（1）在水溶液（μ = 0.5）中的水解动力学，并确定反应的主要中间体和产物。
方法
采用稳定性指示等度液相色谱法研究1的降解速率。采用梯度液相色谱法研究降解产物的时间进程。通过制备液相色谱分离水解产物，并通过1H-NMR和CI-MS进行鉴定。通过电位滴定法获得pKa值。
结果
在36.8℃下，1在水中的pH-速率曲线可用四项速率方程充分描述。中间体被鉴定为伯和仲二乙酸酯以及伯和仲单乙酸酯。最终产物是6-氮杂尿苷。
结论
一个简化的动力学方案可用于描述1、中间体和最终产物的浓度-时间曲线。
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