核苷二苯基磷酸酯的合成及大鼠体内药物动力学

Synthesis and Pharmacokinetics of Five Diaryl Phosphate Triester Derivatives of Zidovudine

AZT的5′-二苯基系列磷酸酯衍生物在体外抗病毒实验中显示了良好的抗HIV病毒活性,具有开发为新型核苷类抗病毒药物的潜力.本文采用PCl3一锅法合成了系列核苷二苯基磷酸酯,并对其纯化后的化合物进行大鼠体内药物动力学规律评价.结果显示该系列衍生物的动力学表现和苯基上取代基的性质有直接联系,且均能改善对AZT的释放,有作为临床抗艾滋病治疗剂的可能.

Diaryl phosphates triester derivatives of AZT were demonstrated great in vitro anti-HIV activity. Five pro-drugs were synthesized through tricoordinated phosphate chemistry. The overall pharmacokinetics in rat plasma was associated with the structure of the diaryl phosphate triester compounds.the magnitude of which varied considerably with the nature of the aryl substituent. The diaryl phosphate triester pro-drugs of AZT proved the tendency of sustained release of AZT, longer residence time in vivo and increased plasma concentration of AZT. The 5 diaryl phosphate triester pro-drugs exhibited the success in the potency of clinical anti-HIV therapeutics.