(Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-iodopyrimidine-2,4(1H,3H)-dione | 830358-75-3

• 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-iodopyrimidine-2,4(1H,3H)-dione
• 英文别名: (Z)-5-iodouracil-2',3'-di-O-benzyl-4',5'-didehydro-5',6'-dideoxy-L-ascorbic acid；5-iodo-1-[(2Z)-2-[5-oxo-3,4-bis(phenylmethoxy)furan-2-ylidene]ethyl]pyrimidine-2,4-dione
• CAS: 830358-75-3
• 化学式: C₂₄H₁₉IN₂O₆
• 分子量: 558.329
• InChiKey: RGHGJHIODOIVDB-ODLFYWEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

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-iodopyrimidine-2,4(1H,3H)-dione 在 copper(l) iodide 、 四(三苯基膦)钯 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 6-(4-bromophenyl)-3-[(2Z)-2-[5-oxo-3,4-bis(phenylmethoxy)furan-2-ylidene]ethyl]furo[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Synthesis and Antiviral and Cytostatic Evaluations of the New C-5 Substituted Pyrimidine and Furo[2,3-d]pyrimidine 4‘,5‘-Didehydro-l-ascorbic Acid Derivatives

  摘要：

  The novel C-5 alkynyl substituted pyrimidine (1-11) and furo[2,3-d] pyrimidine derivatives (12-22) of L-ascorbic acid were synthesized by coupling of 5-iodouracil-4',5'- didehydro-5',6'-dideoxy-L-ascorbic acid with terminal alkynes by using Sonogashira cross-coupling reaction conditions. The new compounds were evaluated for their cytostatic and antiviral activities. Among all evaluated compounds, the octynyl-substituted uracil derivative of L-ascorbic acid (3) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50 = 2-12 mu M). Pyrimidine derivatives of L-ascorbic acid containing p-substituted phenylacetylene groups (8-11) displayed also a rather pronounced (IC50 = 3- 37 mu M) inhibitory effect toward all tumor cell lines. From the bicyclic series of compounds, 6-butylfuro[ 2,3-d] pyrimidine derivative (12) and 6-p-bromophenylfuro[2,3-d] pyrimidine derivative (19) showed the highest cytostatic activity (IC50) 4.5- 20 mu M), particularly against malignant leukemia (L1210) and T-lymphocyte (Molt4/C8 and CEM) cells. Compounds 3 and 9 showed specific albeit moderate activity against cytomegalovirus (CMV, Davis strain, EC50 = 1.8 and 3.8 AM, respectively, for compounds 3 and 9) at a similar to 5-fold lower concentration than that required to show cytotoxicity.

  DOI：

  10.1021/jm070324z
• 作为产物：
  描述：

  5-碘尿嘧啶 、 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-iodopyrimidine-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

文献信息

• Synthesis and Antiviral and Cytostatic Evaluations of the New C-5 Substituted Pyrimidine and Furo[2,3-<i>d</i>]pyrimidine 4‘,5‘-Didehydro-<scp>l</scp>-ascorbic Acid Derivatives
  作者：Tatjana Gazivoda、Mario Šokčević、Marijeta Kralj、Lidija Šuman、Krešimir Pavelić、Erik De Clercq、Graciela Andrei、Robert Snoeck、Jan Balzarini、Mladen Mintas、Silvana Raić-Malić

  DOI：10.1021/jm070324z

  日期：2007.8.1

  The novel C-5 alkynyl substituted pyrimidine (1-11) and furo[2,3-d] pyrimidine derivatives (12-22) of L-ascorbic acid were synthesized by coupling of 5-iodouracil-4',5'- didehydro-5',6'-dideoxy-L-ascorbic acid with terminal alkynes by using Sonogashira cross-coupling reaction conditions. The new compounds were evaluated for their cytostatic and antiviral activities. Among all evaluated compounds, the octynyl-substituted uracil derivative of L-ascorbic acid (3) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50 = 2-12 mu M). Pyrimidine derivatives of L-ascorbic acid containing p-substituted phenylacetylene groups (8-11) displayed also a rather pronounced (IC50 = 3- 37 mu M) inhibitory effect toward all tumor cell lines. From the bicyclic series of compounds, 6-butylfuro[ 2,3-d] pyrimidine derivative (12) and 6-p-bromophenylfuro[2,3-d] pyrimidine derivative (19) showed the highest cytostatic activity (IC50) 4.5- 20 mu M), particularly against malignant leukemia (L1210) and T-lymphocyte (Molt4/C8 and CEM) cells. Compounds 3 and 9 showed specific albeit moderate activity against cytomegalovirus (CMV, Davis strain, EC50 = 1.8 and 3.8 AM, respectively, for compounds 3 and 9) at a similar to 5-fold lower concentration than that required to show cytotoxicity.
• Novel Pyrimidine and Purine Derivatives of <scp>l</scp>-Ascorbic Acid:  Synthesis and Biological Evaluation
  作者：Silvana Raić-Malić、Antonija Hergold-Brundić、Ante Nagl、Mira Grdiša、Krešimir Pavelić、Erik De Clercq、Mladen Mintas

  DOI：10.1021/jm991017z

  日期：1999.7.1

  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.