从 5-氟尿嘧啶环核苷到苯并稠合的六元和七元环与嘧啶和嘌呤碱基相连：从区分抗癌药物到诱导细胞凋亡的转变。
From 5-fluorouracil acyclonucleosides to benzo-fused six- and seven-membered rings linked to pyrimidine and purine bases: the shift from differentiating anticancer agents to apoptotic inducers.
机构信息
Universidad de Granada, Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, c/Campus de Cartuja s/n, 18071 Granada, Spain ++34 958 243848 ; ++34 958 243845 ;
出版信息
Expert Opin Drug Discov. 2008 Oct;3(10):1223-35. doi: 10.1517/17460441.3.10.1223.
BACKGROUND
(RS)-1-{[3-(2-Hydroxyethoxy)-1-isopropoxy]propyl}-5-fluorouracil proved to be a good differentiating agent against rhabdomyosarcoma cells.
OBJECTIVE
As lipophilicity is known to affect the anticancer activity, the synthesis of a wide range of 5-fluorouracil derivatives linked to benzo-fused seven-membered rings was undertaken.
METHODS
The decision was then made to change 5-fluorouracil for uracil, with the prospect of finding an antiproliferative agent endowed with a new mechanism of action. Later on, pyrimidines were substituted for purines. Completing a structure-activity relationship study, a series of isosteric seven-membered derivatives were prepared.
RESULTS/CONCLUSION: Finally, molecules were designed in which both structural entities (such as the benzoheterocycle and the purine) were linked through a strong C-C bond. The anticancer activity for the most active compounds was correlated with their capability to induce apoptosis.
背景
（RS）-1-[[3-(2-羟乙氧基）-1-异丙氧基]丙基]-5-氟尿嘧啶被证明是一种很好的横纹肌肉瘤细胞分化剂。
目的
由于亲脂性已知会影响抗癌活性，因此合成了一系列与苯并稠合的七元环相连的 5-氟尿嘧啶衍生物。
方法
然后决定用尿嘧啶代替 5-氟尿嘧啶，以期发现一种具有新作用机制的增殖抑制剂。后来，嘧啶取代了嘌呤。完成结构-活性关系研究后，制备了一系列等排七元环衍生物。
结果/结论：最后，设计了通过强 C-C 键连接两个结构实体（如苯并杂环和嘌呤）的分子。最活跃化合物的抗癌活性与其诱导细胞凋亡的能力相关。
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