8-carbamoyl-3-(2-trimethylsilylethoxy)methylimidazo<5,1-d>-1,2,3,5-tetrazin-4(3H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑四嗪类
• 英文名称: 8-carbamoyl-3-(2-trimethylsilylethoxy)methylimidazo<5,1-d>-1,2,3,5-tetrazin-4(3H)-one
• 英文别名: 4-Oxo-3-(2-trimethylsilylethoxymethyl)imidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide
• 化学式: C₁₁H₁₈N₆O₃Si
• 分子量: 310.388
• InChiKey: XTAAYHOHCWQHCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  6

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	3-N-hydroxymethyl temozolomide	1161825-88-2	C6H6N6O3	210.152
  ——	2,2-dimethyl-propionic acid 8-carbamoyl-4-oxo-imidazo[5,1-d][1,2,3,5]tetrazin-3-ylmethyl ester	1161825-92-8	C11H14N6O4	294.27
  替莫唑胺	temozolomide	85622-93-1	C6H6N6O2	194.153
  ——	8-carbamoyl-3-(but-2-ynyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one	1161825-96-2	C9H8N6O2	232.202
  ——	8-carbamoyl-3-[3-(trimethylsilyl)prop-2-ynyl]imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one	1161825-97-3	C11H14N6O2Si	290.357
  ——	3-cyclopropylmethyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide	1161825-91-7	C9H10N6O2	234.217
  ——	8-carbamoyl-3,4-dihydro-4-oxoimidazo<5,1-d>-1,2,3,5-tetrazin-3-ylacetic acid	157466-98-3	C7H6N6O4	238.162
  ——	8-carbamoyl-3-[(carbamoyl)methyl]imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one	1161825-65-5	C7H7N7O3	237.178
  ——	4-oxo-3-(2-oxobutyl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide	1161825-90-6	C9H10N6O3	250.217
  ——	methyl 2-(8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)acetate	1161825-89-3	C8H8N6O4	252.189

反应信息

• 作为反应物：
  描述：

  8-carbamoyl-3-(2-trimethylsilylethoxy)methylimidazo<5,1-d>-1,2,3,5-tetrazin-4(3H)-one 在 三氟化硼 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 氯仿 、 乙腈 为溶剂， 生成 替莫唑胺
  参考文献：
  名称：

  Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position

  摘要：

  对N-3位取代的咪唑四氮唑类化合物的合成和生物评价进行了描述。

  DOI：

  10.1039/c7md00554g
• 作为产物：
  描述：

  2-(三甲基硅烷基)乙氧甲基氯 以 乙醚 、 二甲基亚砜 为溶剂， 反应 88.0h， 生成 8-carbamoyl-3-(2-trimethylsilylethoxy)methylimidazo<5,1-d>-1,2,3,5-tetrazin-4(3H)-one
  参考文献：
  名称：

  Wang, Yongfeng; Stevens, Malcolm F. G.; Thomson, William T., Journal of the Chemical Society. Perkin transactions I, 1995, # 21, p. 2783 - 2789

  摘要：

  DOI：

文献信息

• Synthesis of [3-<i>N</i>-¹¹C-methyl]temozolomide via<i>in situ</i>activation of 3-<i>N</i>-hydroxymethyl temozolomide and alkylation with [¹¹C]methyl iodide
  作者：Jonas Eriksson、Rolph Van Kooij、Robert C. Schuit、Femke E. Froklage、Jaap C. Reijneveld、N. Harry Hendrikse、Albert D. Windhorst

  DOI：10.1002/jlcr.3251

  日期：2015.3

  Temozolomide is a chemotherapeutic drug that is mainly used in the treatment of primary glioblastoma multiforme and recurrent high-grade glioma. Here, we report an efficient good manufacturing practice compliant method for the synthesis of [3-N-11C-methyl]temozolomide from 3-N-hydroxymethyl temozolomide that cleaves off formaldehyde in situ and becomes activated towards alkylation with [11C]methyl iodide. The labelling method was developed for an on-going patient study in which the predictive value of [3-N-11C-methyl]temozolomide and positron emission tomography on the outcome of temozolomide treatment is being investigated. The precursor was reacted with [11C]methyl iodide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene in acetonitrile, heated at stepwise increasing temperature. Purification by semipreparative HPLC with pharmaceutical grade eluent and filtration gave approximately 10 mL sterile product solution ready for injection containing 1.55 ± 0.38 GBq (n = 5), the specific activity was 88 ± 25 GBq/µmol and the radiochemical purity was 98.5 ± 1.9%. 13C-NMR spectroscopy confirmed the labelled position after colabelling with 11C and 13C.

  替莫唑胺是一种主要用于治疗原发性多形性胶质母细胞瘤和高级别胶质瘤复发的化疗药物。在此，我们报道了一种符合良好生产规范的高效合成方法，用于从3-N-羟甲基替莫唑胺合成[3-N-11C-甲基]替莫唑胺，该方法能在原位裂解甲醛并激活其与[11C]甲基碘的烷基化反应。这种标记方法是为一项正在进行的研究设计的，该研究旨在探讨[3-N-11C-甲基]替莫唑胺和正电子发射断层扫描技术对替莫唑胺治疗结果的预测价值。在存在1,8-二氮杂双环[5.4.0]十一碳-7-烯的情况下，将前体与[11C]甲基碘在乙腈中反应，并逐步升高温度加热。通过半制备型高效液相色谱法，使用符合药用级别的洗脱液和过滤，获得了约10毫升无菌产品溶液，可直接用于注射，其中含有1.55 ±0.38吉贝克（n=5），比活性为88 ±25吉贝克/微摩尔，放射化学纯度为98.5 ±1.9%。通过13C-核磁共振光谱法，在与11C和13C共同标记后确认了标记位置。
• [EN] 3-SUBSTITUTED-4-0X0-3, 4-DIHYDRO-IMIDAZO- [5, 1-D] [1,2,3,5] -TETRAZINE-8-CARBOXYLIC ACID AMIDES AS ANTICANCER AGENTS<br/>[FR] AMIDES D'ACIDES 4-OXO-3,4-DIHYDROIMIDAZO[5,1-D][1,2,3,5-TÉTRAZINE-8-CARBOXYLIQUES SUBSTITUÉS EN POSITION 3 ET LEUR UTILISATION
  申请人：PHARMINOX LTD

  公开号：WO2009077741A3

  公开（公告）日：2009-12-03
• Synthesis and growth-inhibitory activities of imidazo[5,1-<i>d</i>]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position
  作者：David Cousin、Marc G. Hummersone、Tracey D. Bradshaw、Jihong Zhang、Christopher J. Moody、Magdalena B. Foreiter、Helen S. Summers、William Lewis、Richard T. Wheelhouse、Malcolm F. G. Stevens

  DOI：10.1039/c7md00554g

  日期：——

  The synthesis and biological evaluation of imidazotetrazines substituted at N-3 is described.

  对N-3位取代的咪唑四氮唑类化合物的合成和生物评价进行了描述。
• Wang, Yongfeng; Stevens, Malcolm F. G.; Thomson, William T., Journal of the Chemical Society. Perkin transactions I, 1995, # 21, p. 2783 - 2789
  作者：Wang, Yongfeng、Stevens, Malcolm F. G.、Thomson, William T.、Shutts, Bruce P.

  DOI：——

  日期：——