5′-脱氧-5-氟胞苷类衍生物的合成及其抗肿瘤活性  

Synthesis and antitumor activities of novel 5′-deoxy-5-fluorocytidine derivatives

作　　者：余建鑫[1] 张万年[1] 姚建忠[1] 盛春泉[1] 吴广[1] 

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《中国药物化学杂志》2007年第3期135-139,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(20302013)

摘　　要：目的设计并合成具有抗肿瘤活性的5′-脱氧-5-氟胞苷类衍生物。方法2′,3′-O-二乙酰-5′-脱氧-5-氟胞苷在三氯氧磷存在下与1,2,4-三唑缩合得到1-(2′,3′-O-二乙酰-5′-脱氧-β-D-呋喃核糖)-4-(1,2,4-三唑-1-基)-5-氟嘧啶-2-(1H)-酮(3),后者用不同的亲核基团取代核苷C-4位上的三唑基团,制备一系列含有烷基胺、烷氧基和脒基的5′-脱氧-5-氟胞苷类衍生物。结果合成了15个未见报道的新化合物,化合物的结构经1H-NMR、FAB-MS及元素分析确证。结论抗肿瘤活性测试表明,其中某些化合物的活性与对照药物卡培他滨相当,对肺癌、结肠癌、乳腺癌和肝癌细胞显示出较好的抑制活性。Aim To design and synthesize 5＇-deoxy-5-fluorocytidine derivatives as antitumor drugs. Methods A series of 5＇-deoxy-5-fluorocytidine alkylamine, alkoxyl and amidine derivatives were synthesized by dis- placement of triazole group at C-4 of 1-（2＇, 3＂-O-diacetyl-5＇-deoxy-β-D-ribofuranosyl）-4-（1, 2, 4-triazol-1- yl）-5-fluoropyrimidin-2- （1 H）-one, which was obtained conveniently by condensation between 2＇, 3＇- O-diacetyl-5＇-deoxy- 5-fluorocytidine and 1, 2, 4-triazole in the presence of POC13. Results Fifteen new compounds were prepared, all of the products were confirmed by ^1H-NMR, FAB-MS, and elemental analysis. Conclusion Antitumor activity results indicated that some of the title compounds had similar inhibitory effect on the lung cancer cell, breast cancer cell, liver cancer cell, and colon cancer cell as capecitabine did.

关 键 词：5'-脱氧-5-氟胞苷 卡培他滨 抗肿瘤活性 MTT法 

分 类 号：R914.5[医药卫生—药物化学] R73-3[医药卫生—药学]