Yang Lin, Zeng Rong, Li Chao, Li Gang, Qiao Renzhong, Hu Liming, Li Zelin
State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
Bioorg Med Chem Lett. 2009 May 1;19(9):2566-9. doi: 10.1016/j.bmcl.2009.03.044. Epub 2009 Mar 17.
A novel approach to synthesize chitosan-O-isopropyl-5'-O-d4T monophosphate conjugate was developed. Chitosan-d4T monophosphate prodrug with a phosphoramidate linkage was efficiently synthesized through Atherton-Todd reaction. In vitro drug release studies in pH 1.1 and 7.4 indicated that chitosan-O-isopropyl-5'-O-d4T monophosphate conjugate prefers to release the d4T 5'-(O-isopropyl)monophosphate than free d4T for a prolonged period. The results suggested that chitosan-O-isopropyl-5'-O-d4T monophosphate conjugate may be used as a sustained polymeric prodrug for improving therapy efficacy and reducing side effects in antiretroviral treatment.
开发了一种合成壳聚糖-O-异丙基-5'-O-d4T单磷酸酯缀合物的新方法。通过Atherton-Todd反应高效合成了具有氨基磷酸酯键的壳聚糖-d4T单磷酸酯前药。在pH 1.1和7.4条件下的体外药物释放研究表明，壳聚糖-O-异丙基-5'-O-d4T单磷酸酯缀合物在较长时间内更倾向于释放d4T 5'-(O-异丙基)单磷酸酯而非游离的d4T。结果表明，壳聚糖-O-异丙基-5'-O-d4T单磷酸酯缀合物可用作持续的聚合物前药，以提高抗逆转录病毒治疗的疗效并减少副作用。
