Synthesis and Crystal Structure of N1-(2-(4-Bromo-2-nitrophenoxy)-2-dimethyl acyloxymethyl)-5-fluorouracil

The title compound N1-（2-（4-bromo-2-nitrophenoxy）-2-dimethyl acyloxymethyl）-5-fluorouracil（C15H13BrFN3O7, Mr = 446.19） was synthesized and structurally characterized by ^1H-NMR, -（13）C-NMR, ESI-MS and single-crystal X-ray diffraction. The compound crystallizes in triclinic, space group P1, with a = 8.3325（6）, b = 10.1808（13）, c = 11.8194（16） A, α = 73.194（12）, β= 72.351（9）, γ = 89.509（8）o, V = 911.2（2） A^3, Z = 2, T = 300.79（10） K, μ（Cu Kα） = 3.578 mm^-1, Dc = 1.626 g/cm3, F（000） = 448.0, GOF = 1.060, 5723 reflections measured（8.232≤2θ≤139.592°）, 3339 unique（Rint = 0.0184, Rsigma = 0.0254） which were used in all calculations. The final R = 0.0517（I 〉 2s（I）） and wR = 0.1494（all data）. Hydrogen bonds and π-π interactions together stabilize the structure of the molecule. The preliminary biological test shows that the title compound has good antitumor activity against A549 in vitro and lower toxicity to normal cells.

脑靶向N1-羧酰-5-氟尿嘧啶系列化合物体外透过血脑屏障抑制肿瘤细胞活性

目的研究已合成的N1-羧酰-5-氟尿嘧啶系列化合物体外透血脑屏障抑制人星形胶质瘤细胞的活性。方法利用台盼蓝染色显微镜法观察计数方法考查N1-羧酰-5-氟尿嘧啶系列前体药物体外对人星形胶质瘤细胞增殖活性抑制作用;并通过培养大鼠脑毛细血管内皮细胞,建立体外模拟血脑屏障模型,观察N1-维甲酰-5-氟尿嘧啶和N1-山梨酰-5-氟尿嘧啶体外透过血脑屏障模型对人星形胶质瘤细胞增殖活性抑制作用。结果该系列化合物抗人星形胶质瘤活性较5-氟尿嘧啶增强,而对大鼠脑毛细血管内皮细胞的毒性降低;N1-维甲酰-5-氟尿嘧啶和N1-山梨酰-5-氟尿嘧啶较5-氟尿嘧啶透过BBB抑制人星形胶质瘤细胞的作用更好。结论N1-羧酰-5-氟尿嘧啶系列化合物抗人星形胶质瘤活性及透过体外血脑屏障能力都较5-氟尿嘧啶好。