3-methyl-3,4-dihydro-4-oxopyrazolo<5,1-d>-1,2,3,5-tetrazine-8-carboxamide | 90521-24-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-methyl-3,4-dihydro-4-oxopyrazolo<5,1-d>-1,2,3,5-tetrazine-8-carboxamide
• 英文别名: Temozolomide；temozolamide；3-methyl-3,4-dihydro-4-oxopyrazolo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide；3-Methyl-4-oxopyrazolo[5,1-d][1,2,3,5]tetrazine-8-carboxamide
• CAS: 90521-24-7
• 化学式: C₆H₆N₆O₂
• 分子量: 194.153
• InChiKey: NHXAXFAKTMZCOV-UHFFFAOYSA-N

物化性质

• 熔点：
  265-267 °C (decomp)
• 沸点：
  498.2±37.0 °C(Predicted)
• 密度：
  1.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 3-methyl-3,4-dihydro-4-oxopyrazolo<5,1-d>-1,2,3,5-tetrazine-8-carboxamide 在 硫酸 作用下， 以64%的产率得到N,N'-Bis(3,4-dihydro-4-oxo-3-methylimidazo[5,1-d][1,2,3,5]tetrazin-8-ylcarbonyl)diaminomethane
  参考文献：
  名称：

  Antitumour imidazotetrazines. Part 39. Synthesis of bis(imidazotetrazine)s with saturated spacer groups

  摘要：

  双(咪唑四嗪) (16) 的结构与抗肿瘤药物米唑仑 (1a) 和替莫唑胺 (1b) 相关，但通过咪唑[5,1-d][1,2,3,5]四嗪环系的N(3)–N(3′)原子相连，由5-氮杂咪唑-4-羧酰胺 (8) 和二异氰酸酯 (15) 反应制备而成。含/不含硫和氧杂原子的多亚甲基连接体的存在并未显著影响与未连接的咪唑四嗪米唑仑和替莫唑胺特征相关的酸稳定性、碱催化分解、抗肿瘤活性或DNA碱基烷基化偏好。

  DOI：

  10.1039/b005652i
• 作为产物：
  描述：

  5-重氮咪唑-4-甲酰胺 、 异氰酸甲酯 以 乙酸乙酯 为溶剂， 反应 192.0h， 以85%的产率得到3-methyl-3,4-dihydro-4-oxopyrazolo<5,1-d>-1,2,3,5-tetrazine-8-carboxamide
  参考文献：
  名称：

  Pyrazole derivatives. 5. Synthesis and antineoplastic activity of 3-(2-chloroethyl)-3,4-dihydro-4-oxopyrazolo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide and related compounds

  摘要：

  Two pyrazolotetrazine derivatives were synthesized as the analogous prodrugs of the light-sensitive antineoplastic agents dacarbazine and BIC. Both the pyrazole derivatives are stable under ordinary light illumination. Biological evaluation of these pyrazoles revealed that the compound containing a 2-chloroethyl function (6a) demonstrated good antineoplastic activity in experimental animals, but the one containing a methyl function (6b) was inactive. The inactivity of compound 6b may suggest that compound 6a and related imidazotetrazines may simply act as biological alkylating agents per se rather than as prodrugs. The information could also imply that the postulated dealkylation mechanism for the triazene derivatives should be reexamined.

  DOI：

  10.1021/jm00158a041

文献信息

• CHENG C. C.; ELSLAGER E. F.; WERBEL L. M.; PRIEBE S. R.; LEOPOLD W. R., J. MED. CHEM., 29,(1986) N 8, 1544-1547
  作者：CHENG C. C.、 ELSLAGER E. F.、 WERBEL L. M.、 PRIEBE S. R.、 LEOPOLD W. R.

  DOI：——

  日期：——
• Pyrazole derivatives. 5. Synthesis and antineoplastic activity of 3-(2-chloroethyl)-3,4-dihydro-4-oxopyrazolo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide and related compounds
  作者：C. C. Cheng、Edward F. Elslager、Leslie M. Werbel、Wilbur R. Leopold

  DOI：10.1021/jm00158a041

  日期：1986.8

  Two pyrazolotetrazine derivatives were synthesized as the analogous prodrugs of the light-sensitive antineoplastic agents dacarbazine and BIC. Both the pyrazole derivatives are stable under ordinary light illumination. Biological evaluation of these pyrazoles revealed that the compound containing a 2-chloroethyl function (6a) demonstrated good antineoplastic activity in experimental animals, but the one containing a methyl function (6b) was inactive. The inactivity of compound 6b may suggest that compound 6a and related imidazotetrazines may simply act as biological alkylating agents per se rather than as prodrugs. The information could also imply that the postulated dealkylation mechanism for the triazene derivatives should be reexamined.
• Antitumour imidazotetrazines. Part 39. Synthesis of bis(imidazotetrazine)s with saturated spacer groups
  作者：Jill Arrowsmith、Sharon A. Jennings、David A. F. Langnel、Richard T. Wheelhouse、Malcolm F. G. Stevens

  DOI：10.1039/b005652i

  日期：——

  Bis(imidazotetrazine)s (16), related in structure to the antitumour agents mitozolomide (1a) and temozolomide (1b), but linked through the N(3)–N(3′) atoms of the imidazo[5,1-d][1,2,3,5]tetrazine ring-systems, are prepared by interaction of 5-diazoimidazole-4-carboxamide (8) and diisocyanates (15). The presence of the polymethylene linker with/without sulfur and oxygen heteroatoms does not substantially affect the acid stability, base-catalysed decomposition, antitumour activity or DNA base alkylation preference characteristic of the unlinked imidazotetrazines mitozolomide and temozolomide.

  双(咪唑四嗪) (16) 的结构与抗肿瘤药物米唑仑 (1a) 和替莫唑胺 (1b) 相关，但通过咪唑[5,1-d][1,2,3,5]四嗪环系的N(3)–N(3′)原子相连，由5-氮杂咪唑-4-羧酰胺 (8) 和二异氰酸酯 (15) 反应制备而成。含/不含硫和氧杂原子的多亚甲基连接体的存在并未显著影响与未连接的咪唑四嗪米唑仑和替莫唑胺特征相关的酸稳定性、碱催化分解、抗肿瘤活性或DNA碱基烷基化偏好。