高分子药物研究——ⅩⅦ. 二羟烷基嘧啶与N,N’-双(2-氯乙基) 二氯磷酰胺缩聚物的合成及其抗肿瘤活性研究

本文通过七种二羟烷基嘧啶单体与N,N’一双(2-氯乙基)氯磷酰胺进行缩聚反应,制得了七种新的含核酸碱基或其类似物和氮芥的聚磷酸酯,用核磁、红外光谱及元素分析确定了单体和聚合物的结构。部分聚合物试验结果表明,既含氮芥又含5-氟尿嘧啶的聚合物具有较高的抗癌活性和较低的毒性,聚合物(Ⅲ_a)对小鼠艾氏腹水癌的抑制率可达66％。

CHEMOTHERAPEUTIC POLYMER XVII THE SYNTHESIS AND ANTITUMOR ACTIVITY OF POLYPHOSPHATES CONTAINING BOTH NUCLEIC ACID BASE AND NITROGEN MUSTARD

Seven new polyphosphates containing both nucleic acid base and nitrogen mustard were prepared by reacting the monomers, i.e. l,3-dihydroxyalkyl-5-fluorouracil (IIa,b,g), 1,3-dihydro-xyalkyluracil (IIe,d) and 1,3-dihydroxyalkylthymine (IIe,f) with N,N-bis (2-chloroethyl) phospho-ramidic dichlorid (I). The monomers and polymers were structurally characterized by 'H-NMR, IR spectra and elemental analysis. All of the polymers obtained are soluble in water. The antitumor activity of some of these polymers were tested against Ehrlish ascites in mice. The results showed that the polyphosphates containing both 5-fluorouracil and nitrogen mustard exhibit the lower toxicity and higher antitumor activity. The inhibition ratio of the polymer (IIIa) is 66%.