(Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione | 318239-85-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-[(2Z)-2-[5-oxo-3,4-bis(phenylmethoxy)furan-2-ylidene]ethyl]-5-(trifluoromethyl)pyrimidine-2,4-dione
• CAS: 318239-85-9
• 化学式: C₂₅H₁₉F₃N₂O₆
• 分子量: 500.431
• InChiKey: CNDOSXSVVXIDRN-ODLFYWEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 以52.1%的产率得到(Z)-1-(2-(3,4-dihydroxy-5-oxofuran-2(5H)-ylidene)ethyl)-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  L-抗坏血酸的新型嘧啶和嘌呤衍生物：合成，一维和二维1H和13C NMR研究，细胞生长抑制和抗病毒评估。

  摘要：

  内酯环的C-2'（6-10）或C-2'和C-3'（11-15）位置含有游离羟基的1-抗坏血酸的新型C-5取代的嘧啶衍生物的合成被描述。2,3-O，O-二苄基-1-抗坏血酸的16-氯-和6-（N-吡咯基）嘌呤衍生物的脱苄基作用（16和17）得到了在C-2'处含有羟基的新化合物（ 18）和C-2'和C-3'（19和20）。从它们的一维和二维（1）H和（13）C NMR谱图和连接性，推导出C4'C5'双键的Z和E构型以及化合物6-9的内酯环的位置。 NOESY和HMBC光谱。在该系列所有评估的化合物中，化合物15和18表现出最佳的抑制活性。含有5-（三氟甲基）尿嘧啶的化合物15显示出对所有人类恶性细胞系（IC（50）：5.6-12.8 microM）的显着抑制活性，除了对人类T淋巴细胞。此外，该化合物还通过增加G2 / M期的细胞数量影响细胞周期，并诱导SW 620和MiaPaCa-2细胞凋亡。

  DOI：

  10.1016/j.bmc.2004.09.052
• 作为产物：
  描述：

  5-三氟甲基尿嘧啶 、 5,6-di-O-acetyl-2,3-di-O-benzyl-L-ascorbic acid 在 硫酸氢铵 、 三氟甲磺酸三甲基硅酯 、 六甲基二硅氮烷 作用下， 生成 (Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Novel Pyrimidine and Purine Derivatives of l-Ascorbic Acid:  Synthesis and Biological Evaluation

  摘要：

  The novel pyrimidine derivatives 1-6 of 2,3-dibenzyl-4,5-didehydro-5,6-dideoxy-L-ascorbic acid were synthesized by the condensation of pyrimidine bases with 5,6-diacetyl-2,3-dibenzyl-L-ascorbic acid (DDA). Both N-9 (7) and N-7 (8) regioisomers were obtained in the reaction of 6-chloropurine with 5-acetyl-6-bromo-2,3-dibenzyl-L-ascorbic acid (ABDA), while the reaction of 6-(N-pyrrolyl)purine with ABDA afforded exclusively the N-9 isomer 9. Structures of all newly prepared compounds were deduced from the chemical shifts in H-1 and C-13 NMR spectra, as well as connectivities in 2D homo- and heteronuclear correlation spectra. An unambiguous proof of the structure and conformation of 7 was obtained by X-ray crystallographic analysis. Compounds 1-9 were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), murine leukemia (L1210/0), murine mammary carcinoma (FM3A), and human T-lymphocytes (Molt4/C8 and CEM/0), as well as antiviral activities against varicella-zoster virus (TK(+)VZV and TK(-)VZV) and cytomegalovirus (CMV). The compound 6 containing a trifluoromethyl-substituted uracil ring exhibited marked antitumor activity. The N-7-substituted purine regioisomer 8 had greater inhibitory effects on the murine L1210/0 and human CEM/0 cell lines than the N-9 isomer 7. Compound 9 with the B-purine-substituted pyrrolo moiety had a more pronounced selective cytostatic activity against human (Molt4/C8 and CEM-0) cell lines than murine (L1210/0 and FM3A/O) and human (MiaPaCa2, MCF7, HeLa, and Hep2) tumor cell lines and normal fibroblasts (Hef522). The compound 6 exhibited the most potent antiviral activities against TK(+)VZV, TK(-)VZV, and CMV, albeit at concentrations that were only slightly lower than the cytotoxic concentrations.

  DOI：

  10.1021/jm991017z