Martinez A P, Lee W W, Henry D W
J Med Chem. 1977 Mar;20(3):341-4. doi: 10.1021/jm00213a005.
A series of ten S-substituted derivatives of the alpha and beta anomers (1a and 1b) of 2'-deoxy-6-thioguanosine has been prepared by S-alkylation of the parent nucleosides and/or by mercaptide displacement reactions on 6-chloro intermediates. Against L1210 murine leukemia all beta anomers were active but potency was reduced relative to 1b. Most S-alkyl alpha anomers were inactive in this test. Limited testing against P388 murine leukemia showed all alpha-anomer derivatives to be inactive but the beta anomers were more effective than the parent. S-Substitution sharply reduced acute toxicity in both series. In vitro DNA and RNA synthesis inhibition data are also reported. The antitumor activity of these derivatives and of the 2',5'-di-O-acetyl derivatives of 1a and 1b against lymphoid leukemia L1210 is reported. Some results with the lymphocytic leukemia P388 and an in vitro assay of the inhibition of nucleic acid synthesis are also given.
通过对母体核苷进行S-烷基化和/或对6-氯中间体进行硫醇盐置换反应，制备了一系列十种2'-脱氧-6-硫代鸟苷的α和β异头物（1a和1b）的S-取代衍生物。对于L1210小鼠白血病，所有β异头物均具有活性，但相对于1b，其效力有所降低。在该试验中，大多数S-烷基α异头物无活性。针对P388小鼠白血病的有限测试表明，所有α异头物衍生物均无活性，但β异头物比母体更有效。S-取代显著降低了两个系列中的急性毒性。还报告了体外DNA和RNA合成抑制数据。报道了这些衍生物以及1a和1b的2',5'-二-O-乙酰基衍生物对淋巴白血病L1210的抗肿瘤活性。还给出了淋巴细胞白血病P388的一些结果以及核酸合成抑制的体外测定结果。
